[Objectives]To determine the improvement effect of vinegar soaked licorice on liver fibrosis induced by carbon tetrachloride(CCl_(4))combined with high-fat diet in rats.[Methods]Subcutaneous injection of 40%-60%CCl_(4...[Objectives]To determine the improvement effect of vinegar soaked licorice on liver fibrosis induced by carbon tetrachloride(CCl_(4))combined with high-fat diet in rats.[Methods]Subcutaneous injection of 40%-60%CCl_(4)olive oil solution(0.3 mL/100 g)combined with a high-fat diet was used for 5 weeks to establish the rat model with liver fibrosis.After the modeling,the rats were divided into a low dose(0.8 g/kg),a medium dose(2.5 g/kg),a high dose(5 g/kg)group,a colchicine(1.5 mg/kg)positive group,and a vinegar group(2 mL/kg).The serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels in the rats were measured automatically.The serum hyaluronic acid(HA)was detected by radioimmunoassay,and the serum laminin(LN)and procollagen type III peptide(PIIIP)levels were measured by enzyme-linked immunoassay.Liver histopathological morphological changes were observed by HE and Masson staining,and expressions of cytochrome CYP2E1 and transcription factor Nrf2 were detected by immunohistochemistry.[Results]The rat liver fibrosis model was established successfully at the 6~(th)week.Compared with the model group,the levels of ALT,AST,HA,LA,PIIIP,CYP2E1 and Nrf2 of all the examined indexes in the dosing group were decreased(P<0.05).As shown in the pictures of liver pathological tissue sections,the liver fibrosis was significantly alleviated in the positive group and the 3 administration groups.[Conclusions]Vinegar soaked licorice can significantly improve the liver fibrosis induced by carbon tetrachloride combined with high-fat diet in rats,and the effect of the high-dose group was similar to that of the positive group.展开更多
AIM:To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian Decoction(HYRD)on CCl4-induced hepatic fibrosis in rats and its modulation on the transforming growth factor(TGF)β-Smad signaling pathway.METHODS:Fif...AIM:To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian Decoction(HYRD)on CCl4-induced hepatic fibrosis in rats and its modulation on the transforming growth factor(TGF)β-Smad signaling pathway.METHODS:Fifty-six healthy Wistar rats were randomly divided into five groups:normal control group(n=6),CCl4-induced hepatic fibrosis group(n=14) and three treatment groups(the treated rats received HYRD via oral administration at daily dosages of 8.2,2.5 and 0.82 g/kg,respectively)of HYRD(n=12,respectively).Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride solution(CCl4 dissolved in peanut oil,4:6,V/V)with 0.5 mL/100 g body weight for the first time,and then 0.3 mL/100 g body weight twice a week for 8 wk.In the former 2 wk,rats were raised by feedstuffⅠ(80% corn meal,20%lard,0.5%cholesterol).After 2 wk,they were raised by feedstuffⅡ(corn meal and 0.5% cholesterol).Except for the control group,30%alcohol solution was given orally to each rat every other day from the beginning,1 mL for each rat.Liver function parameters and hepatic hydroxyproline content were detected by chromatometry.Serum levels of hyaluronic acid(HA),typeⅣcollagen(CIV),typeⅢprecollagen(PCⅢ)and laminin(LN)were assayed with radioimmunoassay.Deposition of collagen was observed with hematoxylin-eosin staining and collagen staining.Gene expression of TGFβ1 and Smad3 were detected with real-time reverse transcriptase-polymerase chain reaction and Western blotting,respectively.RESULTS:The serum levels of alanine transaminase and aspartate transaminase were increased in the model group compared with the control group(P<0.01),and they were decreased in the three treatment groups compared with the model group.The serum levels of total protein and albumin were decreased in the model group and increased in the three treatment groups.The hepatic hydroxyproline content and serum levels of PCⅢ,HA,LN and CIV were markedly increased in the model group compared with the control group,and decreased in the treatment groups.The gene expression of TGFβ1 and Smad3 was enhanced in the model group compared with the control group,and HYRD could down regulate their expression.CONCLUSION:HYRD can inhibit hepatic fibrosis induced by CCl4 in rats,which is probably associated with its down-regulation on fibrogenic signal transduction of TGFβ-Smad pathway.展开更多
AIM To investigate the protective effects of Foeniculum vulgare root bark(FVRB), a traditional Uyghur medicine, against carbon tetrachloride(CCl4)-induced hepatic fibrosis in mice. METHODS Mice were randomly divided i...AIM To investigate the protective effects of Foeniculum vulgare root bark(FVRB), a traditional Uyghur medicine, against carbon tetrachloride(CCl4)-induced hepatic fibrosis in mice. METHODS Mice were randomly divided into eight groups(n = 20 each). Except for the normal control group, mice in the rest groups were intraperitoneally injected(i.p.) with 0.1% CCl4-olive oil mixture at 10 m L/kg twice a week to induce liver fibrosis. After 4 wk, mice were treated concurrently with the 70% ethanol extract of FVRB(88, 176, 352 and 704 mg/kg, respectively) daily by oral gavage for 4 wk to evaluate its protective effects. Serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride(TG), hexadecenoic acid(HA), laminin(LN), glutathione(GSH), superoxide dismutase(SOD), and malondialdehyde(MDA) in liver tissues were measured. Hematoxylin-eosin(H and E) staining and Masson trichrome(MT) staining were performed to assess histopathological changes in the liver. The expression of transforming growth factor β1(TGF-β1), matrix metalloprotein 9(MMP-9) and metallopeptidase inhibitor 1(TIMP-1) was detected by immunohistochemical analysis. Additionally, TGF-β1 and alpha-smooth muscle actin(α-SMA) protein expression was measured by Western blot.RESULTS A significant reduction in serum levels of AST, ALT, TG, HA and LN was observed in the FVRB-treated groups, suggesting that FVRB displayed hepatoprotective effects. Also, the depletion of GSH, SOD, and MDA accumulation in liver tissues was suppressed by FVRB. The expression of TGF-β1, MMP-9 and TIMP-1 determined by immunohistochemistry was markedly reduced in a dose-dependent manner by FVRB treatment. Furthermore, protective effects of FVRB against CCl4-induced liver injury were confirmed by histopathological studies. Protein expression of TGF-β1 and α-SMA detected by Western blot was decreased by FVRB treatment.CONCLUSION Our results indicate that FVRB may be a promising agent against hepatic fibrosis and its possible mechanisms are inhibiting lipid peroxidation and reducing collagen formation in liver tissue of liver fibrosis mice.展开更多
AIM: To study the mechanism underlying carbon tetrachloride (CCl4)-induced alterations of protein synthesis in liver. METHODS: Male Sprague-Dawley rats were given CCl4 (1 mL/100 g body weight) and 3H-leucine incorpora...AIM: To study the mechanism underlying carbon tetrachloride (CCl4)-induced alterations of protein synthesis in liver. METHODS: Male Sprague-Dawley rats were given CCl4 (1 mL/100 g body weight) and 3H-leucine incorporation. Malondialdehyde (MDA) level in the liver, in vitro response of hepatocyte nuclei nucleotide triphosphatase (NTPase) to free radicals, and nuclear export of total mRNA with 3'-poly A+ were measured respectively. Survival response of HepG2 cells to CCl4 treatment was assessed by methyl thiazolyl tetrazolium. Km and Vmax values of nuclear envelope NTPase activity in liver of rats treated with CCl4 were assayed by a double-reciprocal plot. RESULTS: The protein synthesis was inhibited while the MDA level was signif icantly increased in liver of rats treated with CCl4. In addition, CCl4 decreased the NTPase binding capacity of nuclear envelope (Km value) in cultured HepG2 cells. Moreover, in vitro ferrous radicals from Fenton's system suppressed the NTPase activity of liver nuclear envelope in a dose-dependent manner. Down-regulation of the nuclear envelope NTPase activity indicated a lower energy provision for nucleocytoplasmic transport of mRNA molecules, an evidence in CCl4-treated HepG2 cells correspondingly supported by the nuclear sequestration of poly (A)+ mRNA molecules in morphological hybridization research. CONCLUSION: Inhibition of mRNA transport, suggestive of decreased NTPase activity of the nuclear envelope, may be involved in carbon tetrachloride-inhibited protein synthesis in liver.展开更多
Objective:To evaluate a novel polyherbal formulation(BSVT)containing the standardized extracts from the leaves of Boerhavia diffusa,Solidago virgaurea,Vitex negundo,and thymoquinone in CCl4 induced hepatorenal toxicit...Objective:To evaluate a novel polyherbal formulation(BSVT)containing the standardized extracts from the leaves of Boerhavia diffusa,Solidago virgaurea,Vitex negundo,and thymoquinone in CCl4 induced hepatorenal toxicity in rats.Methods:A total of 36 rats were divided into six groups including normal control,CCl4(2 mL/kg,i.p.),CCl4(2 mL/kg,i.p.)+Cystone?(750 mg/kg p.o.),CCl4(2 mL/kg,i.p.)+BSVT(25 mg/kg,p.o.),CCl4(2 mL/kg,i.p.)+BSVT(50 mg/kg,p.o.),and CCl4(2 mL/kg,i.p.)+BSVT(100 mg/kg,p.o.).All treatments were given for four weeks.Serum levels of aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,total protein,serum urea,blood urea nitrogen and creatinine were assessed.Superoxide dismutase,malondialdehyde,and glutathione peroxidase were evaluated in tissue homogenate.The histopathological study of liver and kidney tissues was also done.Results:Aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,serum urea,blood urea nitrogen and creatinine were significantly elevated(P<0.001)while total protein was considerably reduced in the CCl4 group as compared to the normal control(P<0.001),which indicated hepatorenal toxicity.In addition,superoxide dismutase and glutathione peroxidase activities were significantly decreased(P<0.001)while malondialdehyde levels were increased markedly(P<0.001).Treatment with BSVT formulation recovered these parameters towards a normal level in a dose-dependent manner.Conclusions:BSVT formulation ameliorates the hepatorenal toxicity in a dose-dependent manner.Furthermore,clinical studies are required to confirm its efficacy.展开更多
By comparing the testing data of the hydrochemistry components and organic pollution of karst water sample in Jinan with large amount of historical data, the author finds the long-existing problem of carbon tetrachlor...By comparing the testing data of the hydrochemistry components and organic pollution of karst water sample in Jinan with large amount of historical data, the author finds the long-existing problem of carbon tetrachloride pollution and the great change of hydrochemical characteristics of karst water in eastern suburbs of Jinan. Since karst water is the main water-supply source in eastern suburbs of Jinan, these problems have greatly affected the safety of water supply. Based on the analysis of hydrogeological condition in eastern suburbs of Jinan, this thesis discusses the causes of carbon tetrachloride pollution and hydrochemical variation with hydrogeochemical theories so as to protect the precious karst groundwater and Jinan spring water. It is found that through research and analysis that there are mainly two causes of carbon tetrachloride pollution and hydrochemical variation: the vulnerability of karst water in this area; the other being the serious pollution in this area caused by remaining pollution sources of the last century.展开更多
[Objectives] The aim was to study the protection effect of Qiwei Jingganling on carbon tetrachloride-induced acute liver injury in mice and its mechanism of action. [Methods]Total 60 mice were randomly and evenly divi...[Objectives] The aim was to study the protection effect of Qiwei Jingganling on carbon tetrachloride-induced acute liver injury in mice and its mechanism of action. [Methods]Total 60 mice were randomly and evenly divided into 6 groups,normal group,model group,silymarin group( 150 mg/kg),high-dose Qiwei Jingganling group( 8 g/kg,crude drug),middle-dose Qiwei Jingganling group( 4 g/kg,crude drug) and low-dose Qiwei Jingganling group( 2 g/kg,crude drug). The mice were administered orally once a day according to the amount of10 m L/kg,and 10-day continuous administration was carried out. After 2 h of the last administration,0. 12% CCl4 peanut oil solution( 10 m L/kg) was injected intraperitoneally to all the mice except those in the normal group to establish acute liver injury model. After 16 h,the blood of the mice was collected from the eyeballs,and their liver tissues were collected. The levels of alanine aminotransferase( ALT),aspartate aminotransferase( AST),superoxide dismutase( SOD),malondialdehyde( MDA) and glutathione peroxidase( GSH-Px) in the sera were determined by biochemical methods,and the contents of tumor necrosis factor-α( TNF-α),interleukin-1β( IL-1β) and interleukin-6( IL-6) in the liver tissues were determined with enzyme-linked immunosorbent assays( ELISA). [Results]Qiwei Jingganling significantly reduced the activities or content of ALT,AST and MDA in serum of mice with liver injury( P < 0. 05,P < 0. 01),increased the activities of SPD and GSH-Px( P < 0. 05,P < 0. 01) and down-regulated the expression levels of IL-1β,IL-6 and TNF-α in liver tissue( P < 0. 05,P < 0. 01).[Conclusions]Qiwei Jingganling has a good protection effect on CCl4-induced acute liver injury in mice,which may be related to the inhibition of oxidative stress and inhibition of inflammatory responses.展开更多
[Objectives] To study the protection of compatibility of Saikosapon d and Baicalin on carbon tetrachloride( CCl_4) injured L-02 cells. [Methods] Normal human hepatocyte cell line L-02 cells were cultured in vitro,and ...[Objectives] To study the protection of compatibility of Saikosapon d and Baicalin on carbon tetrachloride( CCl_4) injured L-02 cells. [Methods] Normal human hepatocyte cell line L-02 cells were cultured in vitro,and CCl_4 was used to induce hepatocellular injury. Interventions were carried out with Saikosaponin d and Baicalin at different dosage. The proliferation of L-02 cells in each group was determined by methylthiazolyl tetrazolium( MTT) assay; the levels of AST and ALT in the culture supernatants were detected by enzyme-linked immunosorbent assay( ELISA); the expressions of TLR4 and NFκBp65 proteins in each group were determined by immunohistochemistry.[Results] In the CCl_4 injured group,the proliferation of L-02 cells was significantly declined,the levels of AST and ALT in cell culture medium were significantly increased,and the expressions of TLR4 and NFκBp65 in L-02 cells were increased; after the intervention of Saikosaponin d and Baicalin,1. 75 μg/mL group and 1. 5 μg/mL group had an effect of promoting the proliferation of L-02 cells and could reduce the levels of AST and ALT in the cell culture medium,and TLR4 and NFκBp65 proteins in L-02 cells also had a certain inhibitory effect. [Conclusions] The compatibility of Saikosapon d and Baicalin has a certain protective effect on CCl_4 injured L-02 cells. The protection mechanism may be related with its down-regulating TLR4-NFκB signaling pathway and reducing the inflammation.展开更多
<span style="font-family:Verdana;"><i><span style="font-family:Verdana;"><i></span></i></span><span style="font-family:Verdana;"><span s...<span style="font-family:Verdana;"><i><span style="font-family:Verdana;"><i></span></i></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">S</span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;"></i></span></i></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">-allyl-L-cysteine (SAC) is an organosulfur compound derived from aged garlic extract (</span><span style="font-family:Verdana;">AGE</span><span style="font-family:Verdana;">). Studies have reported that AGE possesses bioprotective capacity, including antidiabetic, antimicrobial, antioxidant, and antitumor effects. The present study examined the protective effects of SAC against carbon tetrachloride (CCl</span><sub><span style="font-family:Verdana;">4</span></sub><span style="font-family:Verdana;">) induced hepatotoxicity in rats. Ten male Wistar rats aged 11 - 12 weeks were randomly divided into two groups (five rats/group) as control and SAC groups. All rats had </span><span style="font-family:Verdana;">ad</span> <span style="font-family:Verdana;">libitum</span><span style="font-family:Verdana;"> access to water, and the SAC group received water containing SAC intragastrically (200 mg/kg) once daily for five consecutive weeks. In the fifth experimental week, 50% CCl</span><sub><span style="font-family:Verdana;">4</span></sub><span style="font-family:Verdana;"> in olive oil (1 mL/kg) was administered intraperitoneally three times a week to induce liver injury in both groups. Rats were sacrificed at 24 hours after the last CCl</span><sub><span style="font-family:Verdana;">4</span></sub><span style="font-family:Verdana;"> injection, and liver tissues were excised for histopathological, immunohistochemical and antioxidant analyses. The rats in the SAC group did not show abnormal behavior, such as decreased water intake or food consumption, during the experimental period. Body weights in all groups did not change significantly over the experimental period. Histopathological analysis showed that the percentage of hepatic steatosis was lower in the SAC group at 12.75% ± 3.74% compared to 24.64% ± 5.29% in the control group (</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">p</span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;"></i></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> < 0.05). The percentage of cytochrome P4502E1 (CYP2E1) distribution area in the SAC group was also lower at 19.61% ± 6.18% compared with 25.22% ± 6.21% in the control group (</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">p</span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;"></i></span></i></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> < 0.05). These results suggest that SAC can alleviate CCl</span><sub><span style="font-family:Verdana;">4</span></sub><span style="font-family:Verdana;">-induced liver damage by decreasing hepatic steatosis and reducing CYP2E1 expression in rats.展开更多
AIM:To investigate the effect of T helper(Th)17/T regulatory(Treg)cells on hepatic fibrosis in mice and its possible mechanism.METHODS:Hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride....AIM:To investigate the effect of T helper(Th)17/T regulatory(Treg)cells on hepatic fibrosis in mice and its possible mechanism.METHODS:Hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride.Hepatic pathological changes were observed by hematoxylin and eosin staining;the protein levels of interleukin(IL)-6,transforming growth factor(TGF)-βandα-smooth muscle actin(SMA)in liver tissue were determined by Western blotting;and the frequency of Th17 and Treg cells in the liver was estimated by flow cytometry.In addition,hepatic stellate cells were isolated from healthy mouse liver and co-cultured with Th17 or Treg cells.Immunofluorescence staining and Western blotting were performed to determine the change in HSC activation.RESULTS:In the model group,there were different degrees of fibroplasia,degeneration and necrosis.The protein levels of IL-6,TGF-βandα-SMA in liver tissue were significantly higher than those in the control group at 12 wk(P<0.05).Compared with the control group,the frequency of Th17 cells in the model group was increased but the frequency of Treg cells decreased gradually.Furthermore,at 4,8 and 12 wk,there were significant differences in the number of Th17 cells(0.52%±0.16%,1.46%±0.24%,and2.60%±0.41%,respectively,P<0.05)and Treg cells(2.99%±0.40%,2.16%±0.50%,and 1.49%±0.34%,respectively,P<0.05).In vitro,Th17 cells promoted,whereas Treg cells inhibited the expression ofα-SMA,both in a dose-dependent manner,compared with the control group.CONCLUSION:Th17/Treg imbalance exists in mice with liver fibrosis,which potentially promotes liver fibrosis via HSC activation.展开更多
AIM:To investigate the role of caspase-12 and its downstream targets in carbon tetrachloride(CCl4)-induced hepatocyte apoptosis.METHODS:The role of caspase-12 was determined by using caspase-12 knock-out(-/-)mice.CCl4...AIM:To investigate the role of caspase-12 and its downstream targets in carbon tetrachloride(CCl4)-induced hepatocyte apoptosis.METHODS:The role of caspase-12 was determined by using caspase-12 knock-out(-/-)mice.CCl4(300μL/kg body weight)or vehicle(corn oil)was administered to caspase-12+/+or caspase-12-/-mice as a single intraperitoneal injection.The animals were sacrificed24 h after the CCl4 treatment.Blood was collected to evaluate liver function by the measurement of the activity of alanine aminotransferase.Liver samples were used for the measurements of reactive oxygen species using plasma malondialdehyde as biomarker,hepatocyte apoptosis was evaluated via terminal transferasemediated d UTP nick-end labeling and controlled by morphologic study,and cytochrome C release and caspase activations were measured by Western blotting.RESULTS:Administration of a low dose of CCl4resulted in hepatocyte apoptosis and acute liver injury in wild-type mice.CCl4 also induced the generation of reactive oxygen species and induction of endoplasmic reticulum stress in the liver followed by activations of caspase-12,-9 and-3 as well as release of small amounts of cytochrome C.However,in the CCl4-treated caspase-12-/-mice,activation of caspase-9 and-3 were significantly attenuated(P<0.05);no effect was seen in cytochrome C release.CCl4-induced apoptosis and liver damage was markedly reduced in caspase-12-/-mice compared to caspase-12+/+mice(P<0.05).The active form of caspase-8 was not detected in either caspase-12+/+or caspase-12-/-mice.There was no significant different in the formation of reactive oxygen species in the livers of caspase-12+/+and caspase-12-/-mice treated with CCl4.CONCLUSION:Caspase-12 plays a pivotal role in CCl4-induced hepatic apoptosis through the activation of the downstream effector caspase-3 directly and/or indirectly via capase-9 activation.展开更多
AIM: To investigate the expression and role of activin A in a mouse model of acute chemical liver injury. METHODS: Acute liver injury in C57BL/6 male mice was induced by intraperitoneal injection with carbon tetrachlo...AIM: To investigate the expression and role of activin A in a mouse model of acute chemical liver injury. METHODS: Acute liver injury in C57BL/6 male mice was induced by intraperitoneal injection with carbon tetrachloride (CCl4 ) (0.5 mL/kg, body weight) dissolved in olive oil (1:19 v/v). Mice were sacrificed 1, 3, 5 and 7 d after the treatment. The levels of alanine aminotrans-ferase (ALT) and aspartate aminotransferase (AST) in serum were examined and pathological changes of liver observed by hematoxylin and eosin staining to evaluate the liver injury. Activin A protein levels in serum and hepatic tissue homogenate of mice were detected by enzyme-linked immunosorbent assay, and the expres-sion pattern of activin A protein in livers of mice was examined by immunohistochemistry. Activin type Ⅱ A receptor (ActRⅡA) and Smad3 expressions in the liver were analyzed by real-time quantitative reverse transcription-polymerase chain reaction. In order to further investigate the role of activin A, we also utilized activin A blocking experiment by anti-activin A antibody (500 μg/kg, body weight) injection into mouse tail vein. RESULTS: In CCl4-treated mice, serum ALT and AST levels were significantly increased, compared with that in control mice (P<0.01). Furthermore, the serious necrosis was observed around hepatic portal areas in CCl4-treated mice. Simultaneously, activin A levels in serum and hepatic tissue homogenate of mice treated with CCl4 for 1, 3 and 5 d increased significantly, com-pared with that in control mice (P<0.01). Activin A protein expression in hepatocytes not within the ne-crotic area was also upregulated in mice following CCl4 treatment. Not only activin A, but also ActRⅡA and activin signaling molecule Smad3 mRNA expressions in injury liver induced by CCl4 were significantly higher than that in control liver. In addition, levels of serum ALT and AST in CCl4-treated mice were significantly decreased by injection of anti-activin A antibody to block endogenous activin A action, compared with that in CCl4-treated mice by injection of immunoglobulin G instead of anti-activin A antibody (P<0.01), and the severity of liver injury was also reduced remarkably. CONCLUSION: These data show that activin A is in-volved in CCl4-induced acute liver injury. Blocking ac-tivin A actions may be a therapeutic approach for acute liver injury.展开更多
Objective:To investigate the hepatoprotective activity of Averroha carambola fruit extract against carbon tetrachloride induced hepatic injury.Methods:Hepatotoxicity was induced on albino mice by intraperitoneal admin...Objective:To investigate the hepatoprotective activity of Averroha carambola fruit extract against carbon tetrachloride induced hepatic injury.Methods:Hepatotoxicity was induced on albino mice by intraperitoneal administration of CCl<sub>4</sub>.half an hour after the administration of the last dose of the extract of Averroha carambola fruit.Aqueous extract of the fruit of Averroha carambola was administered at a dose of 0.9 g/kg body weight once daily for seven days.The hepatic injury and its prevention was assessed by the estimation of serum activities of alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,alkaline phosphates（ALP）,glutathione level and histopathological studies of liver.Results:Pre-treatment of mice with the fruit extract of Averrhoea carambola significantly reduced serum levels of ALT,AST and ALP enzyme and significantly increased the liver reduced glutathione levels 24 h after the administration of carbon tetrachloride.A marked improvement in the enzyme activities and the liver reduced glulathione level was observed in the pre-treated mice 4 days after the administration of carbon tetrachloride. Histopathological studies provided supportive evidence for the biochemical analvsis. Conclusions:The aqueous extract of the fruit of Averrhoea carambola has hepatoprotective effect against carbon tetrachloride induced liver damage in mice.展开更多
AIM:To investigate whether a virus constitutively expressing active Akt is useful to prevent cirrhosis induced by carbon tetrachloride(CCl4).METHODS:Using cre-loxp technique,we created an Ad-myr-HA-Akt virus,in which ...AIM:To investigate whether a virus constitutively expressing active Akt is useful to prevent cirrhosis induced by carbon tetrachloride(CCl4).METHODS:Using cre-loxp technique,we created an Ad-myr-HA-Akt virus,in which Akt is labeled by a HA tag and its expression is driven by myr promoter.Further,through measuring enzyme levels and histological structure,we determined the efficacy of this Ad-myrHA-Akt virus in inhibiting the development of cirrhosis induced by CCl4in rats.Lastly,using western blotting,we examined the expression levels and/or phosphorylation status of Akt,apoptotic mediators,endothelial nitric oxide synthase(eNOS),and markers for hepatic stellate cells activation to understand the underlying mechanisms of protective role of this virus.RESULTS:The Ad-myr-HA-Akt virus was confirmed using polymerase chain reaction amplification of inserted Akt gene and sequencing for full length of inserted fragment,which was consistent with the sequence reported in the GenBank.The concentrations of Admyr-HA-Akt and adenoviral enhanced green fluorescent protein(Ad-EGFP)virus used in the current study were5.5×1011vp/mL.The portal vein diameter,peak velocity of blood flow,portal blood flow and congestion index were significantly increased in untreated,saline and Ad-EGFP cirrhosis groups when compared to normal control after the virus was introduced to animal through tail veil injection.In contrast,these parameters in the Akt cirrhosis group were comparable to normal control group.Compared to the normal control,the liver function(Alanine aminotransferase,Aspartate aminotransferase and Albumin)was significantly impaired in the untreated,saline and Ad-EGFP cirrhosis groups.The Akt cirrhosis group showed significant improvement of liver function when compared to the untreated,saline and Ad-EGFP cirrhosis groups.The Hyp level and portal vein pressure in Akt cirrhosis groups were also significantly lower than other cirrhosis groups.The results of HE and Van Gieson staining indicated that Akt group has better preservation of histological structure and less fibrosis than other cirrhosis groups.The percentage of apoptotic cell was greatly less in Akt cirrhosis group than in other cirrhosis groups.Akt group showed positive HA tag and an increased level of phosphorylated Akt as well as decreased levels of Fas.In contrast,Caspase-3 and Caspase-9 levels in Akt group were significantly lower than other cirrhosis groups.Noticeable decrease of DR5 andα-SMA and increase of phosphorylated eNOS were observed in the Akt group when compared to other cirrhosis groups.The NO level in liver was significantly higher in Akt group than other cirrhosis groups,which was consistent with the level of phosphorylated eNOS in these groups.CONCLUSION:This study suggest that Ad-myr-HA-Akt virus is a useful tool to prevent CCl4-induced cirrhosis in rat model and Akt pathway may be a therapeutic target for human cirrhosis.展开更多
Objective:To investigate the hepatoproteetivc ami antioxidant activity of pentagamavunon-0(PGV-0) against CCl-4-induced hepatic injury in rats.Methods:The groups of animals were administered with PGV-0 at die doses 2....Objective:To investigate the hepatoproteetivc ami antioxidant activity of pentagamavunon-0(PGV-0) against CCl-4-induced hepatic injury in rats.Methods:The groups of animals were administered with PGV-0 at die doses 2.5.5,10,and 20 mg/kg b.w.,p.o.once in a day for 6 days and at day 7 the animals were administrated with carbon tetrachloride(CClj)(20%,2 ml/kg b.w.in liquid paraffin dp.).The effect of PGV-0 on serum transaminase(SGPT),alkaline phosphates(ALP and total bilirubin were determined in CCl-4-indueed hepatotoxicity in rats.Further,the effects of PGV-0 on glutathione(GSU) content,cutalase(CAT) and NO free radical scavenging activity also were investigated.Results:The results demonstrated that PCV-0 significantly reduced the activity of SGPT,serum ALP and total bilirubin in CCl-4 induced rat hepatotoxicity.PGV-0 has effect on the antioxidant and free radical defense system.It prevented the depletion level of GSH and decrease activity of CAT in CCl-4-induced liver injury in rats.PCV-0 also demonstrated the free radical scavenger effects on NO free radical scavenging activity with ES value of 32.32μM. Convulsion:All of our findings suggests that PGV-0 could protect the liver cells from CCl-4- induced liver damages and the mechanism may through the antioxidative effect of PGV-0 to prevent the accumulation of free radicals and protect the liver damage.展开更多
Objective:To investigate the hepatoprotective and antioxidant activities of Alchornea cordifolia (A.cordifolia) leaf extract.Methods:Various solvent fractions of the methanol extract of the leaf of the plant.4.cordifo...Objective:To investigate the hepatoprotective and antioxidant activities of Alchornea cordifolia (A.cordifolia) leaf extract.Methods:Various solvent fractions of the methanol extract of the leaf of the plant.4.cordifolia Mull.Arg(Fam:Euphorbiaceae) were evaluated for hepatoprotective activity by carbon tetrachloride-induced liver damage in rats.The degree of protection was measured by using biochemical parameters such as serum glutamate oxalate transaminase(SGOT/ AST),serum glutamate pyruvate transaminase(SCPT/ALT),alkaline phosphatase(ALP) and total bilirubin.The in vitro antioxidant activity of the extract was also evaluated by the I,I-diphenyl 2-picrylhydrazyl(DPPH) free radical scavenging assay.The extract was subjected to preliminary phytoehemical screening.Results:The ethyl acetate and chloroform fractions,at a dose of 300 mg/kg,produced significant(P【0.05) hepatoprolection by decreasing the activities of the serum enzymes and bilirubin while there were marked scavenging of the DPPH free radicals by the fractions.The effects were comparable to those of the standard drugs used for the respective experiments,silymarin and ascorbic acid.Alkaloids,flavonoids,saponins and tannins were delected in the phylochemical screening.Conclusion:From this study,it was concluded that the plant of A.cordifolia possesses hepatoprotective as well as antioxidant activities and these activities reside mainly in the ethyl acetate and acetone fractions of methanol leaf extract.展开更多
Objective:To determine the antioxidant and hepatoprotective potential of methanol extract of rhizome of Curcuma angustifolia(MECA)against carbon tetrachloride(CCl4)-induced hepatic damage in vitro and in vivo.Methods:...Objective:To determine the antioxidant and hepatoprotective potential of methanol extract of rhizome of Curcuma angustifolia(MECA)against carbon tetrachloride(CCl4)-induced hepatic damage in vitro and in vivo.Methods:DPPH,ABTS and reducing power assays were performed to estimate the antioxidant effect of MECA.In vitro cytotoxicity of MECA against HepG2 cells was evaluated,whereas serum biochemical parameters and levels of antioxidative enzymes were measured in vivo and in vitro.Additionally,histopathological studies were estimated in order to investigate the hepatoprotective efficacy of MECA.Furthermore,GC-MS analysis of the extract was performed to identify the chemical components.Results:MECA exhibited strong antioxidant activity and attenuated CCl4-induced decrease in the viability of HepG2 cells.Additionally,MECA significantly restored the ALT,AST,ALP,TP and albumin level in comparison with the CCl4 group.After pre-treatment with MECA,effects of SOD,CAT and GSH were increased as well as lipid peroxidation amount decreased on CCl4-induced hepatotoxicity in in vitro and in vivo model.Furthermore,histopathological observation confirmed that MECA reduced liver injury induced by CCl4 in rats.GC-MS analysis confirmed the presence of bioactive constituents such as α-tocopherol(12.27%),phytol(7.61%),squalene(3.71%),β-sitosterol(2.19%),eugenol(2.59%),curcumenol(1.20%),β-elemene(1.00%)and eucalyptol(0.89%).Conclusions:MECA contains antioxidant and hepatoprotective constituents such asα-tocopherol,phytol,squalene and eugenol and exerts hepatoprotective effect both in vitro and in vivo.展开更多
The electrochemical reduction characteristics of carbon tetrachloride (CT) were investigated using cyclic voltammetry in this study. In addition, the difference in reduction mechanisms of CT between Master Builders...The electrochemical reduction characteristics of carbon tetrachloride (CT) were investigated using cyclic voltammetry in this study. In addition, the difference in reduction mechanisms of CT between Master Builders' iron and the catalyzed Fe-Cu process was discussed. The results showed that CT was reduced directly on the surface of copper rather than by atomic hydrogen produced at the cathode in the catalyzed Fe-Cu process. The reduction was realized largely by atomic hydrogen in Master Builders' iron. The entire CT in 350 ml aqueous solution with 320 mgL was reduced to trichloromethane and dichloromethane in 2.25 h when 100 g of scrap iron with FeCu ratio of 10:1 (ww) were used. Moreover, the reduction rate slowed with time. CT could be reduced at acidic, neutral and alkaline pH from solution by Fe-Cu bimetallic media, but the mechanisms were di?erent. The degradation rate was not significantly in?uenced by pH in the catalyzed Fe-Cu process; in Master Builders' iron it clearly increased with decreasing pH. The kinetics of the reductions followed pseudo-first order in both cases. Furthermore, the reductions under acidic conditions proceeded faster than that under the neutral and alkaline conditions. The catalyzed Fe-Cu process was superior to Master Builders' iron in treating CT-containing water and this advantage was particularly noticeable under alkaline conditions. The reduction was investigated in the cathode (Cu) and anode (Fe) compartments respectively, the results showed that the direct reduction pathway played an important role in the reduction by the catalyzed Fe-Cu process. The catalyzed Fe-Cu process is of practical value.展开更多
The isotherm,mechanism and kinetics of carbon tetrachloride(CT) adsorption by polyacrylonitrile-based activated carbon fiber(PAN-ACF) were investigated in batch reactors and a continuous flow reactor,and the regenerat...The isotherm,mechanism and kinetics of carbon tetrachloride(CT) adsorption by polyacrylonitrile-based activated carbon fiber(PAN-ACF) were investigated in batch reactors and a continuous flow reactor,and the regeneration of PAN-ACF was also studied.Freundlich and Dubinin-Radushkevich(D-R) adsorption equations can well describe the adsorption isotherm.CT is mainly adsorbed on the exterior surface of PAN-ACF with low boundary layer effect and rate-controlling step of intra-particle diffusion.The adsorption dynamics in the batch reactor well fits with the pseudo-first-order model,and the breakthrough curves in the continuous flow reactor can be well described by the Yoon-Nelson model.The ACF can be recycled through thermal regeneration,whereas the adsorption capacity decreases from 7.87 to 4.98 mg/g after the fourth regeneration.78%-94%of CT can be removed from the wastewater of a fluorine chemical plant on a pilot scale,which confirms the efficacy of ACF under industrial conditions.The results indicate that PAN-ACF is applicable to CT removal from wastewater.展开更多
基金Supported by Inner Mongolia Mongolian Medicine Standardization Project(MB2019)Study on the Concoction Method of Licorice and Its Process(myxylxkky2019-04)。
文摘[Objectives]To determine the improvement effect of vinegar soaked licorice on liver fibrosis induced by carbon tetrachloride(CCl_(4))combined with high-fat diet in rats.[Methods]Subcutaneous injection of 40%-60%CCl_(4)olive oil solution(0.3 mL/100 g)combined with a high-fat diet was used for 5 weeks to establish the rat model with liver fibrosis.After the modeling,the rats were divided into a low dose(0.8 g/kg),a medium dose(2.5 g/kg),a high dose(5 g/kg)group,a colchicine(1.5 mg/kg)positive group,and a vinegar group(2 mL/kg).The serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels in the rats were measured automatically.The serum hyaluronic acid(HA)was detected by radioimmunoassay,and the serum laminin(LN)and procollagen type III peptide(PIIIP)levels were measured by enzyme-linked immunoassay.Liver histopathological morphological changes were observed by HE and Masson staining,and expressions of cytochrome CYP2E1 and transcription factor Nrf2 were detected by immunohistochemistry.[Results]The rat liver fibrosis model was established successfully at the 6~(th)week.Compared with the model group,the levels of ALT,AST,HA,LA,PIIIP,CYP2E1 and Nrf2 of all the examined indexes in the dosing group were decreased(P<0.05).As shown in the pictures of liver pathological tissue sections,the liver fibrosis was significantly alleviated in the positive group and the 3 administration groups.[Conclusions]Vinegar soaked licorice can significantly improve the liver fibrosis induced by carbon tetrachloride combined with high-fat diet in rats,and the effect of the high-dose group was similar to that of the positive group.
基金Supported by The Major Project of Applied Basic Research Plan of the Scientific and Technological Department of Tianjin,No.06YFJZJC02900
文摘AIM:To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian Decoction(HYRD)on CCl4-induced hepatic fibrosis in rats and its modulation on the transforming growth factor(TGF)β-Smad signaling pathway.METHODS:Fifty-six healthy Wistar rats were randomly divided into five groups:normal control group(n=6),CCl4-induced hepatic fibrosis group(n=14) and three treatment groups(the treated rats received HYRD via oral administration at daily dosages of 8.2,2.5 and 0.82 g/kg,respectively)of HYRD(n=12,respectively).Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride solution(CCl4 dissolved in peanut oil,4:6,V/V)with 0.5 mL/100 g body weight for the first time,and then 0.3 mL/100 g body weight twice a week for 8 wk.In the former 2 wk,rats were raised by feedstuffⅠ(80% corn meal,20%lard,0.5%cholesterol).After 2 wk,they were raised by feedstuffⅡ(corn meal and 0.5% cholesterol).Except for the control group,30%alcohol solution was given orally to each rat every other day from the beginning,1 mL for each rat.Liver function parameters and hepatic hydroxyproline content were detected by chromatometry.Serum levels of hyaluronic acid(HA),typeⅣcollagen(CIV),typeⅢprecollagen(PCⅢ)and laminin(LN)were assayed with radioimmunoassay.Deposition of collagen was observed with hematoxylin-eosin staining and collagen staining.Gene expression of TGFβ1 and Smad3 were detected with real-time reverse transcriptase-polymerase chain reaction and Western blotting,respectively.RESULTS:The serum levels of alanine transaminase and aspartate transaminase were increased in the model group compared with the control group(P<0.01),and they were decreased in the three treatment groups compared with the model group.The serum levels of total protein and albumin were decreased in the model group and increased in the three treatment groups.The hepatic hydroxyproline content and serum levels of PCⅢ,HA,LN and CIV were markedly increased in the model group compared with the control group,and decreased in the treatment groups.The gene expression of TGFβ1 and Smad3 was enhanced in the model group compared with the control group,and HYRD could down regulate their expression.CONCLUSION:HYRD can inhibit hepatic fibrosis induced by CCl4 in rats,which is probably associated with its down-regulation on fibrogenic signal transduction of TGFβ-Smad pathway.
基金Supported by National Key Technology R&D Program,No.2012BAI30B02
文摘AIM To investigate the protective effects of Foeniculum vulgare root bark(FVRB), a traditional Uyghur medicine, against carbon tetrachloride(CCl4)-induced hepatic fibrosis in mice. METHODS Mice were randomly divided into eight groups(n = 20 each). Except for the normal control group, mice in the rest groups were intraperitoneally injected(i.p.) with 0.1% CCl4-olive oil mixture at 10 m L/kg twice a week to induce liver fibrosis. After 4 wk, mice were treated concurrently with the 70% ethanol extract of FVRB(88, 176, 352 and 704 mg/kg, respectively) daily by oral gavage for 4 wk to evaluate its protective effects. Serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride(TG), hexadecenoic acid(HA), laminin(LN), glutathione(GSH), superoxide dismutase(SOD), and malondialdehyde(MDA) in liver tissues were measured. Hematoxylin-eosin(H and E) staining and Masson trichrome(MT) staining were performed to assess histopathological changes in the liver. The expression of transforming growth factor β1(TGF-β1), matrix metalloprotein 9(MMP-9) and metallopeptidase inhibitor 1(TIMP-1) was detected by immunohistochemical analysis. Additionally, TGF-β1 and alpha-smooth muscle actin(α-SMA) protein expression was measured by Western blot.RESULTS A significant reduction in serum levels of AST, ALT, TG, HA and LN was observed in the FVRB-treated groups, suggesting that FVRB displayed hepatoprotective effects. Also, the depletion of GSH, SOD, and MDA accumulation in liver tissues was suppressed by FVRB. The expression of TGF-β1, MMP-9 and TIMP-1 determined by immunohistochemistry was markedly reduced in a dose-dependent manner by FVRB treatment. Furthermore, protective effects of FVRB against CCl4-induced liver injury were confirmed by histopathological studies. Protein expression of TGF-β1 and α-SMA detected by Western blot was decreased by FVRB treatment.CONCLUSION Our results indicate that FVRB may be a promising agent against hepatic fibrosis and its possible mechanisms are inhibiting lipid peroxidation and reducing collagen formation in liver tissue of liver fibrosis mice.
基金Supported by The National Natural Science Foundation of China,No.30470846
文摘AIM: To study the mechanism underlying carbon tetrachloride (CCl4)-induced alterations of protein synthesis in liver. METHODS: Male Sprague-Dawley rats were given CCl4 (1 mL/100 g body weight) and 3H-leucine incorporation. Malondialdehyde (MDA) level in the liver, in vitro response of hepatocyte nuclei nucleotide triphosphatase (NTPase) to free radicals, and nuclear export of total mRNA with 3'-poly A+ were measured respectively. Survival response of HepG2 cells to CCl4 treatment was assessed by methyl thiazolyl tetrazolium. Km and Vmax values of nuclear envelope NTPase activity in liver of rats treated with CCl4 were assayed by a double-reciprocal plot. RESULTS: The protein synthesis was inhibited while the MDA level was signif icantly increased in liver of rats treated with CCl4. In addition, CCl4 decreased the NTPase binding capacity of nuclear envelope (Km value) in cultured HepG2 cells. Moreover, in vitro ferrous radicals from Fenton's system suppressed the NTPase activity of liver nuclear envelope in a dose-dependent manner. Down-regulation of the nuclear envelope NTPase activity indicated a lower energy provision for nucleocytoplasmic transport of mRNA molecules, an evidence in CCl4-treated HepG2 cells correspondingly supported by the nuclear sequestration of poly (A)+ mRNA molecules in morphological hybridization research. CONCLUSION: Inhibition of mRNA transport, suggestive of decreased NTPase activity of the nuclear envelope, may be involved in carbon tetrachloride-inhibited protein synthesis in liver.
基金funded by the Deanship of Scientific Research(DSR),King Abdulaziz University,Jeddah,under grant no.(G-567-156-1439).
文摘Objective:To evaluate a novel polyherbal formulation(BSVT)containing the standardized extracts from the leaves of Boerhavia diffusa,Solidago virgaurea,Vitex negundo,and thymoquinone in CCl4 induced hepatorenal toxicity in rats.Methods:A total of 36 rats were divided into six groups including normal control,CCl4(2 mL/kg,i.p.),CCl4(2 mL/kg,i.p.)+Cystone?(750 mg/kg p.o.),CCl4(2 mL/kg,i.p.)+BSVT(25 mg/kg,p.o.),CCl4(2 mL/kg,i.p.)+BSVT(50 mg/kg,p.o.),and CCl4(2 mL/kg,i.p.)+BSVT(100 mg/kg,p.o.).All treatments were given for four weeks.Serum levels of aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,total protein,serum urea,blood urea nitrogen and creatinine were assessed.Superoxide dismutase,malondialdehyde,and glutathione peroxidase were evaluated in tissue homogenate.The histopathological study of liver and kidney tissues was also done.Results:Aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,serum urea,blood urea nitrogen and creatinine were significantly elevated(P<0.001)while total protein was considerably reduced in the CCl4 group as compared to the normal control(P<0.001),which indicated hepatorenal toxicity.In addition,superoxide dismutase and glutathione peroxidase activities were significantly decreased(P<0.001)while malondialdehyde levels were increased markedly(P<0.001).Treatment with BSVT formulation recovered these parameters towards a normal level in a dose-dependent manner.Conclusions:BSVT formulation ameliorates the hepatorenal toxicity in a dose-dependent manner.Furthermore,clinical studies are required to confirm its efficacy.
基金supported by the Key Basic Project of Shandong Province:Jinan Urban Geological Survey-Issued in Shandong(2009)046
文摘By comparing the testing data of the hydrochemistry components and organic pollution of karst water sample in Jinan with large amount of historical data, the author finds the long-existing problem of carbon tetrachloride pollution and the great change of hydrochemical characteristics of karst water in eastern suburbs of Jinan. Since karst water is the main water-supply source in eastern suburbs of Jinan, these problems have greatly affected the safety of water supply. Based on the analysis of hydrogeological condition in eastern suburbs of Jinan, this thesis discusses the causes of carbon tetrachloride pollution and hydrochemical variation with hydrogeochemical theories so as to protect the precious karst groundwater and Jinan spring water. It is found that through research and analysis that there are mainly two causes of carbon tetrachloride pollution and hydrochemical variation: the vulnerability of karst water in this area; the other being the serious pollution in this area caused by remaining pollution sources of the last century.
基金Supported by"Bagui Scholars"Special Funds of Guangxi Zhuang Autonomous Region(GCJH[2017]143)
文摘[Objectives] The aim was to study the protection effect of Qiwei Jingganling on carbon tetrachloride-induced acute liver injury in mice and its mechanism of action. [Methods]Total 60 mice were randomly and evenly divided into 6 groups,normal group,model group,silymarin group( 150 mg/kg),high-dose Qiwei Jingganling group( 8 g/kg,crude drug),middle-dose Qiwei Jingganling group( 4 g/kg,crude drug) and low-dose Qiwei Jingganling group( 2 g/kg,crude drug). The mice were administered orally once a day according to the amount of10 m L/kg,and 10-day continuous administration was carried out. After 2 h of the last administration,0. 12% CCl4 peanut oil solution( 10 m L/kg) was injected intraperitoneally to all the mice except those in the normal group to establish acute liver injury model. After 16 h,the blood of the mice was collected from the eyeballs,and their liver tissues were collected. The levels of alanine aminotransferase( ALT),aspartate aminotransferase( AST),superoxide dismutase( SOD),malondialdehyde( MDA) and glutathione peroxidase( GSH-Px) in the sera were determined by biochemical methods,and the contents of tumor necrosis factor-α( TNF-α),interleukin-1β( IL-1β) and interleukin-6( IL-6) in the liver tissues were determined with enzyme-linked immunosorbent assays( ELISA). [Results]Qiwei Jingganling significantly reduced the activities or content of ALT,AST and MDA in serum of mice with liver injury( P < 0. 05,P < 0. 01),increased the activities of SPD and GSH-Px( P < 0. 05,P < 0. 01) and down-regulated the expression levels of IL-1β,IL-6 and TNF-α in liver tissue( P < 0. 05,P < 0. 01).[Conclusions]Qiwei Jingganling has a good protection effect on CCl4-induced acute liver injury in mice,which may be related to the inhibition of oxidative stress and inhibition of inflammatory responses.
基金Supported by Project of Shaanxi Administration of Traditional Chinese Medicine(zy06)Special Project of Education Department of Shaanxi Provincial Government(12JK1016)Program of Shaanxi Provincial Department of Science and Technology(2013jk4023)
文摘[Objectives] To study the protection of compatibility of Saikosapon d and Baicalin on carbon tetrachloride( CCl_4) injured L-02 cells. [Methods] Normal human hepatocyte cell line L-02 cells were cultured in vitro,and CCl_4 was used to induce hepatocellular injury. Interventions were carried out with Saikosaponin d and Baicalin at different dosage. The proliferation of L-02 cells in each group was determined by methylthiazolyl tetrazolium( MTT) assay; the levels of AST and ALT in the culture supernatants were detected by enzyme-linked immunosorbent assay( ELISA); the expressions of TLR4 and NFκBp65 proteins in each group were determined by immunohistochemistry.[Results] In the CCl_4 injured group,the proliferation of L-02 cells was significantly declined,the levels of AST and ALT in cell culture medium were significantly increased,and the expressions of TLR4 and NFκBp65 in L-02 cells were increased; after the intervention of Saikosaponin d and Baicalin,1. 75 μg/mL group and 1. 5 μg/mL group had an effect of promoting the proliferation of L-02 cells and could reduce the levels of AST and ALT in the cell culture medium,and TLR4 and NFκBp65 proteins in L-02 cells also had a certain inhibitory effect. [Conclusions] The compatibility of Saikosapon d and Baicalin has a certain protective effect on CCl_4 injured L-02 cells. The protection mechanism may be related with its down-regulating TLR4-NFκB signaling pathway and reducing the inflammation.
文摘<span style="font-family:Verdana;"><i><span style="font-family:Verdana;"><i></span></i></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">S</span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;"></i></span></i></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">-allyl-L-cysteine (SAC) is an organosulfur compound derived from aged garlic extract (</span><span style="font-family:Verdana;">AGE</span><span style="font-family:Verdana;">). Studies have reported that AGE possesses bioprotective capacity, including antidiabetic, antimicrobial, antioxidant, and antitumor effects. The present study examined the protective effects of SAC against carbon tetrachloride (CCl</span><sub><span style="font-family:Verdana;">4</span></sub><span style="font-family:Verdana;">) induced hepatotoxicity in rats. Ten male Wistar rats aged 11 - 12 weeks were randomly divided into two groups (five rats/group) as control and SAC groups. All rats had </span><span style="font-family:Verdana;">ad</span> <span style="font-family:Verdana;">libitum</span><span style="font-family:Verdana;"> access to water, and the SAC group received water containing SAC intragastrically (200 mg/kg) once daily for five consecutive weeks. In the fifth experimental week, 50% CCl</span><sub><span style="font-family:Verdana;">4</span></sub><span style="font-family:Verdana;"> in olive oil (1 mL/kg) was administered intraperitoneally three times a week to induce liver injury in both groups. Rats were sacrificed at 24 hours after the last CCl</span><sub><span style="font-family:Verdana;">4</span></sub><span style="font-family:Verdana;"> injection, and liver tissues were excised for histopathological, immunohistochemical and antioxidant analyses. The rats in the SAC group did not show abnormal behavior, such as decreased water intake or food consumption, during the experimental period. Body weights in all groups did not change significantly over the experimental period. Histopathological analysis showed that the percentage of hepatic steatosis was lower in the SAC group at 12.75% ± 3.74% compared to 24.64% ± 5.29% in the control group (</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">p</span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;"></i></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> < 0.05). The percentage of cytochrome P4502E1 (CYP2E1) distribution area in the SAC group was also lower at 19.61% ± 6.18% compared with 25.22% ± 6.21% in the control group (</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">p</span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;"></i></span></i></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> < 0.05). These results suggest that SAC can alleviate CCl</span><sub><span style="font-family:Verdana;">4</span></sub><span style="font-family:Verdana;">-induced liver damage by decreasing hepatic steatosis and reducing CYP2E1 expression in rats.
基金Supported by Grants for Scientific Research Innovation Project of Shanghai Education Committee,China,No.13yz040
文摘AIM:To investigate the effect of T helper(Th)17/T regulatory(Treg)cells on hepatic fibrosis in mice and its possible mechanism.METHODS:Hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride.Hepatic pathological changes were observed by hematoxylin and eosin staining;the protein levels of interleukin(IL)-6,transforming growth factor(TGF)-βandα-smooth muscle actin(SMA)in liver tissue were determined by Western blotting;and the frequency of Th17 and Treg cells in the liver was estimated by flow cytometry.In addition,hepatic stellate cells were isolated from healthy mouse liver and co-cultured with Th17 or Treg cells.Immunofluorescence staining and Western blotting were performed to determine the change in HSC activation.RESULTS:In the model group,there were different degrees of fibroplasia,degeneration and necrosis.The protein levels of IL-6,TGF-βandα-SMA in liver tissue were significantly higher than those in the control group at 12 wk(P<0.05).Compared with the control group,the frequency of Th17 cells in the model group was increased but the frequency of Treg cells decreased gradually.Furthermore,at 4,8 and 12 wk,there were significant differences in the number of Th17 cells(0.52%±0.16%,1.46%±0.24%,and2.60%±0.41%,respectively,P<0.05)and Treg cells(2.99%±0.40%,2.16%±0.50%,and 1.49%±0.34%,respectively,P<0.05).In vitro,Th17 cells promoted,whereas Treg cells inhibited the expression ofα-SMA,both in a dose-dependent manner,compared with the control group.CONCLUSION:Th17/Treg imbalance exists in mice with liver fibrosis,which potentially promotes liver fibrosis via HSC activation.
基金Supported by Institutional research grant by the University of Mississippi Medical Center(to Dr.Hua Liu),No.68512250711
文摘AIM:To investigate the role of caspase-12 and its downstream targets in carbon tetrachloride(CCl4)-induced hepatocyte apoptosis.METHODS:The role of caspase-12 was determined by using caspase-12 knock-out(-/-)mice.CCl4(300μL/kg body weight)or vehicle(corn oil)was administered to caspase-12+/+or caspase-12-/-mice as a single intraperitoneal injection.The animals were sacrificed24 h after the CCl4 treatment.Blood was collected to evaluate liver function by the measurement of the activity of alanine aminotransferase.Liver samples were used for the measurements of reactive oxygen species using plasma malondialdehyde as biomarker,hepatocyte apoptosis was evaluated via terminal transferasemediated d UTP nick-end labeling and controlled by morphologic study,and cytochrome C release and caspase activations were measured by Western blotting.RESULTS:Administration of a low dose of CCl4resulted in hepatocyte apoptosis and acute liver injury in wild-type mice.CCl4 also induced the generation of reactive oxygen species and induction of endoplasmic reticulum stress in the liver followed by activations of caspase-12,-9 and-3 as well as release of small amounts of cytochrome C.However,in the CCl4-treated caspase-12-/-mice,activation of caspase-9 and-3 were significantly attenuated(P<0.05);no effect was seen in cytochrome C release.CCl4-induced apoptosis and liver damage was markedly reduced in caspase-12-/-mice compared to caspase-12+/+mice(P<0.05).The active form of caspase-8 was not detected in either caspase-12+/+or caspase-12-/-mice.There was no significant different in the formation of reactive oxygen species in the livers of caspase-12+/+and caspase-12-/-mice treated with CCl4.CONCLUSION:Caspase-12 plays a pivotal role in CCl4-induced hepatic apoptosis through the activation of the downstream effector caspase-3 directly and/or indirectly via capase-9 activation.
基金Supported by The Natural Science Foundation of China,Grants No.30801005,No.81273199and No.81270513the Project of Science and Development of Jilin Province(to Liu ZH)
文摘AIM: To investigate the expression and role of activin A in a mouse model of acute chemical liver injury. METHODS: Acute liver injury in C57BL/6 male mice was induced by intraperitoneal injection with carbon tetrachloride (CCl4 ) (0.5 mL/kg, body weight) dissolved in olive oil (1:19 v/v). Mice were sacrificed 1, 3, 5 and 7 d after the treatment. The levels of alanine aminotrans-ferase (ALT) and aspartate aminotransferase (AST) in serum were examined and pathological changes of liver observed by hematoxylin and eosin staining to evaluate the liver injury. Activin A protein levels in serum and hepatic tissue homogenate of mice were detected by enzyme-linked immunosorbent assay, and the expres-sion pattern of activin A protein in livers of mice was examined by immunohistochemistry. Activin type Ⅱ A receptor (ActRⅡA) and Smad3 expressions in the liver were analyzed by real-time quantitative reverse transcription-polymerase chain reaction. In order to further investigate the role of activin A, we also utilized activin A blocking experiment by anti-activin A antibody (500 μg/kg, body weight) injection into mouse tail vein. RESULTS: In CCl4-treated mice, serum ALT and AST levels were significantly increased, compared with that in control mice (P<0.01). Furthermore, the serious necrosis was observed around hepatic portal areas in CCl4-treated mice. Simultaneously, activin A levels in serum and hepatic tissue homogenate of mice treated with CCl4 for 1, 3 and 5 d increased significantly, com-pared with that in control mice (P<0.01). Activin A protein expression in hepatocytes not within the ne-crotic area was also upregulated in mice following CCl4 treatment. Not only activin A, but also ActRⅡA and activin signaling molecule Smad3 mRNA expressions in injury liver induced by CCl4 were significantly higher than that in control liver. In addition, levels of serum ALT and AST in CCl4-treated mice were significantly decreased by injection of anti-activin A antibody to block endogenous activin A action, compared with that in CCl4-treated mice by injection of immunoglobulin G instead of anti-activin A antibody (P<0.01), and the severity of liver injury was also reduced remarkably. CONCLUSION: These data show that activin A is in-volved in CCl4-induced acute liver injury. Blocking ac-tivin A actions may be a therapeutic approach for acute liver injury.
文摘Objective:To investigate the hepatoprotective activity of Averroha carambola fruit extract against carbon tetrachloride induced hepatic injury.Methods:Hepatotoxicity was induced on albino mice by intraperitoneal administration of CCl<sub>4</sub>.half an hour after the administration of the last dose of the extract of Averroha carambola fruit.Aqueous extract of the fruit of Averroha carambola was administered at a dose of 0.9 g/kg body weight once daily for seven days.The hepatic injury and its prevention was assessed by the estimation of serum activities of alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,alkaline phosphates（ALP）,glutathione level and histopathological studies of liver.Results:Pre-treatment of mice with the fruit extract of Averrhoea carambola significantly reduced serum levels of ALT,AST and ALP enzyme and significantly increased the liver reduced glutathione levels 24 h after the administration of carbon tetrachloride.A marked improvement in the enzyme activities and the liver reduced glulathione level was observed in the pre-treated mice 4 days after the administration of carbon tetrachloride. Histopathological studies provided supportive evidence for the biochemical analvsis. Conclusions:The aqueous extract of the fruit of Averrhoea carambola has hepatoprotective effect against carbon tetrachloride induced liver damage in mice.
文摘AIM:To investigate whether a virus constitutively expressing active Akt is useful to prevent cirrhosis induced by carbon tetrachloride(CCl4).METHODS:Using cre-loxp technique,we created an Ad-myr-HA-Akt virus,in which Akt is labeled by a HA tag and its expression is driven by myr promoter.Further,through measuring enzyme levels and histological structure,we determined the efficacy of this Ad-myrHA-Akt virus in inhibiting the development of cirrhosis induced by CCl4in rats.Lastly,using western blotting,we examined the expression levels and/or phosphorylation status of Akt,apoptotic mediators,endothelial nitric oxide synthase(eNOS),and markers for hepatic stellate cells activation to understand the underlying mechanisms of protective role of this virus.RESULTS:The Ad-myr-HA-Akt virus was confirmed using polymerase chain reaction amplification of inserted Akt gene and sequencing for full length of inserted fragment,which was consistent with the sequence reported in the GenBank.The concentrations of Admyr-HA-Akt and adenoviral enhanced green fluorescent protein(Ad-EGFP)virus used in the current study were5.5×1011vp/mL.The portal vein diameter,peak velocity of blood flow,portal blood flow and congestion index were significantly increased in untreated,saline and Ad-EGFP cirrhosis groups when compared to normal control after the virus was introduced to animal through tail veil injection.In contrast,these parameters in the Akt cirrhosis group were comparable to normal control group.Compared to the normal control,the liver function(Alanine aminotransferase,Aspartate aminotransferase and Albumin)was significantly impaired in the untreated,saline and Ad-EGFP cirrhosis groups.The Akt cirrhosis group showed significant improvement of liver function when compared to the untreated,saline and Ad-EGFP cirrhosis groups.The Hyp level and portal vein pressure in Akt cirrhosis groups were also significantly lower than other cirrhosis groups.The results of HE and Van Gieson staining indicated that Akt group has better preservation of histological structure and less fibrosis than other cirrhosis groups.The percentage of apoptotic cell was greatly less in Akt cirrhosis group than in other cirrhosis groups.Akt group showed positive HA tag and an increased level of phosphorylated Akt as well as decreased levels of Fas.In contrast,Caspase-3 and Caspase-9 levels in Akt group were significantly lower than other cirrhosis groups.Noticeable decrease of DR5 andα-SMA and increase of phosphorylated eNOS were observed in the Akt group when compared to other cirrhosis groups.The NO level in liver was significantly higher in Akt group than other cirrhosis groups,which was consistent with the level of phosphorylated eNOS in these groups.CONCLUSION:This study suggest that Ad-myr-HA-Akt virus is a useful tool to prevent CCl4-induced cirrhosis in rat model and Akt pathway may be a therapeutic target for human cirrhosis.
基金supported in part by Hibah Competition Grants Research(Research No.UGM/FA/754.a/M/05/01) from the Ministry of National Education of Indonesia
文摘Objective:To investigate the hepatoproteetivc ami antioxidant activity of pentagamavunon-0(PGV-0) against CCl-4-induced hepatic injury in rats.Methods:The groups of animals were administered with PGV-0 at die doses 2.5.5,10,and 20 mg/kg b.w.,p.o.once in a day for 6 days and at day 7 the animals were administrated with carbon tetrachloride(CClj)(20%,2 ml/kg b.w.in liquid paraffin dp.).The effect of PGV-0 on serum transaminase(SGPT),alkaline phosphates(ALP and total bilirubin were determined in CCl-4-indueed hepatotoxicity in rats.Further,the effects of PGV-0 on glutathione(GSU) content,cutalase(CAT) and NO free radical scavenging activity also were investigated.Results:The results demonstrated that PCV-0 significantly reduced the activity of SGPT,serum ALP and total bilirubin in CCl-4 induced rat hepatotoxicity.PGV-0 has effect on the antioxidant and free radical defense system.It prevented the depletion level of GSH and decrease activity of CAT in CCl-4-induced liver injury in rats.PCV-0 also demonstrated the free radical scavenger effects on NO free radical scavenging activity with ES value of 32.32μM. Convulsion:All of our findings suggests that PGV-0 could protect the liver cells from CCl-4- induced liver damages and the mechanism may through the antioxidative effect of PGV-0 to prevent the accumulation of free radicals and protect the liver damage.
文摘Objective:To investigate the hepatoprotective and antioxidant activities of Alchornea cordifolia (A.cordifolia) leaf extract.Methods:Various solvent fractions of the methanol extract of the leaf of the plant.4.cordifolia Mull.Arg(Fam:Euphorbiaceae) were evaluated for hepatoprotective activity by carbon tetrachloride-induced liver damage in rats.The degree of protection was measured by using biochemical parameters such as serum glutamate oxalate transaminase(SGOT/ AST),serum glutamate pyruvate transaminase(SCPT/ALT),alkaline phosphatase(ALP) and total bilirubin.The in vitro antioxidant activity of the extract was also evaluated by the I,I-diphenyl 2-picrylhydrazyl(DPPH) free radical scavenging assay.The extract was subjected to preliminary phytoehemical screening.Results:The ethyl acetate and chloroform fractions,at a dose of 300 mg/kg,produced significant(P【0.05) hepatoprolection by decreasing the activities of the serum enzymes and bilirubin while there were marked scavenging of the DPPH free radicals by the fractions.The effects were comparable to those of the standard drugs used for the respective experiments,silymarin and ascorbic acid.Alkaloids,flavonoids,saponins and tannins were delected in the phylochemical screening.Conclusion:From this study,it was concluded that the plant of A.cordifolia possesses hepatoprotective as well as antioxidant activities and these activities reside mainly in the ethyl acetate and acetone fractions of methanol leaf extract.
文摘Objective:To determine the antioxidant and hepatoprotective potential of methanol extract of rhizome of Curcuma angustifolia(MECA)against carbon tetrachloride(CCl4)-induced hepatic damage in vitro and in vivo.Methods:DPPH,ABTS and reducing power assays were performed to estimate the antioxidant effect of MECA.In vitro cytotoxicity of MECA against HepG2 cells was evaluated,whereas serum biochemical parameters and levels of antioxidative enzymes were measured in vivo and in vitro.Additionally,histopathological studies were estimated in order to investigate the hepatoprotective efficacy of MECA.Furthermore,GC-MS analysis of the extract was performed to identify the chemical components.Results:MECA exhibited strong antioxidant activity and attenuated CCl4-induced decrease in the viability of HepG2 cells.Additionally,MECA significantly restored the ALT,AST,ALP,TP and albumin level in comparison with the CCl4 group.After pre-treatment with MECA,effects of SOD,CAT and GSH were increased as well as lipid peroxidation amount decreased on CCl4-induced hepatotoxicity in in vitro and in vivo model.Furthermore,histopathological observation confirmed that MECA reduced liver injury induced by CCl4 in rats.GC-MS analysis confirmed the presence of bioactive constituents such as α-tocopherol(12.27%),phytol(7.61%),squalene(3.71%),β-sitosterol(2.19%),eugenol(2.59%),curcumenol(1.20%),β-elemene(1.00%)and eucalyptol(0.89%).Conclusions:MECA contains antioxidant and hepatoprotective constituents such asα-tocopherol,phytol,squalene and eugenol and exerts hepatoprotective effect both in vitro and in vivo.
基金Project supported by the Hi-Tech Research and Development Program(863) of China (No. 2002AA601270)
文摘The electrochemical reduction characteristics of carbon tetrachloride (CT) were investigated using cyclic voltammetry in this study. In addition, the difference in reduction mechanisms of CT between Master Builders' iron and the catalyzed Fe-Cu process was discussed. The results showed that CT was reduced directly on the surface of copper rather than by atomic hydrogen produced at the cathode in the catalyzed Fe-Cu process. The reduction was realized largely by atomic hydrogen in Master Builders' iron. The entire CT in 350 ml aqueous solution with 320 mgL was reduced to trichloromethane and dichloromethane in 2.25 h when 100 g of scrap iron with FeCu ratio of 10:1 (ww) were used. Moreover, the reduction rate slowed with time. CT could be reduced at acidic, neutral and alkaline pH from solution by Fe-Cu bimetallic media, but the mechanisms were di?erent. The degradation rate was not significantly in?uenced by pH in the catalyzed Fe-Cu process; in Master Builders' iron it clearly increased with decreasing pH. The kinetics of the reductions followed pseudo-first order in both cases. Furthermore, the reductions under acidic conditions proceeded faster than that under the neutral and alkaline conditions. The catalyzed Fe-Cu process was superior to Master Builders' iron in treating CT-containing water and this advantage was particularly noticeable under alkaline conditions. The reduction was investigated in the cathode (Cu) and anode (Fe) compartments respectively, the results showed that the direct reduction pathway played an important role in the reduction by the catalyzed Fe-Cu process. The catalyzed Fe-Cu process is of practical value.
基金Project(2004C33068) supported by the Science and Technology Programs of Zhejiang Province,ChinaProject(20100933B17) supported by the Social Development and Science Research Program of Hangzhou,China
文摘The isotherm,mechanism and kinetics of carbon tetrachloride(CT) adsorption by polyacrylonitrile-based activated carbon fiber(PAN-ACF) were investigated in batch reactors and a continuous flow reactor,and the regeneration of PAN-ACF was also studied.Freundlich and Dubinin-Radushkevich(D-R) adsorption equations can well describe the adsorption isotherm.CT is mainly adsorbed on the exterior surface of PAN-ACF with low boundary layer effect and rate-controlling step of intra-particle diffusion.The adsorption dynamics in the batch reactor well fits with the pseudo-first-order model,and the breakthrough curves in the continuous flow reactor can be well described by the Yoon-Nelson model.The ACF can be recycled through thermal regeneration,whereas the adsorption capacity decreases from 7.87 to 4.98 mg/g after the fourth regeneration.78%-94%of CT can be removed from the wastewater of a fluorine chemical plant on a pilot scale,which confirms the efficacy of ACF under industrial conditions.The results indicate that PAN-ACF is applicable to CT removal from wastewater.
