BACKGROUND C23,an oligo-peptide derived from cold-inducible RNA-binding protein(CIRP),has been reported to inhibit tissue inflammation,apoptosis and fibrosis by binding to the CIRP receptor;however,there are few repor...BACKGROUND C23,an oligo-peptide derived from cold-inducible RNA-binding protein(CIRP),has been reported to inhibit tissue inflammation,apoptosis and fibrosis by binding to the CIRP receptor;however,there are few reports on its role in liver fibrosis and the underlying mechanism is unknown.AIM To explore whether C23 plays a significant role in carbon tetrachloride(CCl4)-induced liver fibrosis.METHODS CCl4 was injected for 6 weeks to induce liver fibrosis and C23 was used beginning in the second week.Masson and Sirius red staining were used to examine changes in fiber levels.Inflammatory factors in the liver were detected and changes inα-smooth muscle actin(α-SMA)and collagen I expression were detected via immu-nohistochemical staining to evaluate the activation of hematopoietic stellate cells(HSCs).Western blotting was used to detect the activation status of the trans-forming growth factor-beta(TGF-β)/Smad3 axis after C23 treatment.RESULTS CCl4 successfully induced liver fibrosis in mice,while tumor necrosis factor-alpha(TNF-α),IL(interleukin)-1β,and IL-6 levels increased significantly and the IL-10 level decreased significantly.Interestingly,C23 inhibited this process.On the other hand,C23 significantly inhibited the activation of HSCs induced by CCl4,which inhibited the expression ofα-SMA and the synthesis of collagen I.In terms of mechanism,C23 can block Smad3 phosphorylation significantly and inhibits INTRODUCTION At present there is no specific and effective drug for treating liver fibrosis caused by acute or chronic injury.Although preclinical research has made breakthroughs,their suitability as clinical treatments is still unknown.The activation of hepatic stellate cells(HSCs)caused by chronic inflammation is a key process in the development of liver fibrosis and activated HSCs expressα-smooth muscle actin(α-SMA)and transdifferentiate into myofibroblasts with proliferation,migration and secretion abilities,synthesizing the extracellular matrix to deposit in the hepatocyte space and subse-quently forming liver fibrosis[1].Although therapeutic strategies have improved due to past few efforts there is no ideal treatment for hepatic fibrosis[2].Extracellular cold inducible RNA binding protein(CIRP)has been shown to play a role in various acute and chronic inflammatory diseases by promoting tissue inflammation and apoptosis and inducing fibrosis through its receptor Toll-like receptor 4(TLR4)[3].C23 is a recognized competitive inhibitor of CIRP that can competitively bind to CIRP receptors and reduce tissue damage in inflammatory diseases[4].C23 has been shown to significantly reduce serum tumor necrosis factor-alpha(TNF-α),IL(interleukin)-6 and IL-1βlevels.In addition,it can reduce tissue TLR4,TNF-α,IL-6 and IL-1βlevels and inhibit the colocalization of CIRP and TLR4,which plays a significant role in systemic inflammation[5].Re-search has shown that CIRP induces the inflammatory phenotype of lung fibroblasts in a TLR4-dependent manner[6].On the other hand,CIRP is associated with markers of fibrosis andα-SMA is significantly positively correlated with CIRP.Cirp-/-mice exhibit attenuated expression ofα-SMA and collagen(COL1A1 and COL3A1),decreased hydroxyproline content,decreased histological fibrosis scores,and improved pulmonary hypertension[7].C23 inhibited the release of TNF-α,the degradation of IκB and the nuclear translocation of NF-κB in CIRP-stimulated macrophages in a dose-dependent manner and C23 treatment significantly increased the serum levels of lactic dehydrogenase,alanine ami-notransferase,IL-6,TNF-αand IL-1βin septic CLP mice[8].Based on previous research we hypothesized that C23 might alleviate liver fibrosis by inhibiting acute and chronic inflammation.As a selective hepatotoxic chemical carbon tetrachloride(CCl4).can induce inflammation and activate HSCs,promoting liver fibrosis.This study reveals the role and mechanism of C23 in CCl4-induced liver fibrosis in mice.at room temperature for 30 minutes.The gray value of each group was calculated after chemiluminescence.展开更多
[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
As an essential amino acid, lysine boosts protein synthesis (Nestor et al1997). Yao et al demonstrated that, lysine also exerts protective effect against the isch-emiclesion of brain. Meanwhile, vitamin C is a natural...As an essential amino acid, lysine boosts protein synthesis (Nestor et al1997). Yao et al demonstrated that, lysine also exerts protective effect against the isch-emiclesion of brain. Meanwhile, vitamin C is a natural antioxidant, which has undisputable protectiveaction against free radical damages. In order to ascertain whether their combination could affordbetter effect, we have investigated the prophylactic effect of the couplant ascorbate-lysine inliver injuries.展开更多
The dectrochemical reduction characteristics of carbon tetrachlofide （CT） were investigated using cyclic voltammetry in this study. In addition, the difference in reduction mechanisms of CT between Master Builders＇...The dectrochemical reduction characteristics of carbon tetrachlofide （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 mg/L was reduced to trichloromethane and dichloromethane in 2.25 h when 100 g of scrap iron with Fe/Cu ratio of 10：1 （w/w） 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 different. The degradation rate was not significantly influenced 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
AIM： To develop a simplified and quick protocol to induce cirrhosis and standardize models of partial liver resection in rats. METHODS： In Fischer F344 rats two modified protocols of phenobarbital-carbon tetrachlori...AIM： To develop a simplified and quick protocol to induce cirrhosis and standardize models of partial liver resection in rats. METHODS： In Fischer F344 rats two modified protocols of phenobarbital-carbon tetrachloride （CCl4） （dilution 50%） gavage to induce cirrhosis （frequency adjusted according to weight, but each subsequent dose was systematically administered） were tested, i.e. the rapid and slow protocols. Prothrombin time （PT） and total bilirubin （TB） were also evaluated. Animals from the rapid group underwent 15% hepatectomy and animals from the slow group underwent 70% hepatectomy. RESULTS： Rapid protocol： This corresponded to 1 gavage/4 d over 6 wk （mortality 30%）. Mean PT was 35.2 ±2.8 s （normal： ld.5 s）, and mean TB was 1.8 ± 0.2 mg/dL （normal： 0.1 mg/dL）. Slow protocol： This cop responded to 1 gavage/6 d over 9 wk （mortality 10%）. Mean PT was 11.8 ± 0.2 s （normal： 14.5 s）, and mean TB was 0.4 ± 0.04 mg/dL （normal： 0.1 mg/dL）. Pathological analyses were performed in both protocols which showed persistent cirrhosis at 3 mo. Rat mortality in the rapid garage group who underwent 15% hepatectomy and in the slow garage group who underwent 70% hepatectomy was 50% and 70%, respectively, CONCLUSION： Our modified model is a simplified method to induce cirrhosis which is rapid （6 to 9 wk）, efficient and stable up to 3 mo. Using this method, ＂Child Pugh A＂ or ＂Child Pugh BC＂ cirrhotic rats were obtained. Our models of cirrhosis and hepatectomy can be used in various situations focusing on postoperative survival.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 possible mechanism of the protective effects of a bioactive fraction, Ganoderma lucidum proteoglycan （GLPG）isolated from Ganoderma luddum mycelia, against carbon tetrachloride-induced liver ...AIM： To investigate the possible mechanism of the protective effects of a bioactive fraction, Ganoderma lucidum proteoglycan （GLPG）isolated from Ganoderma luddum mycelia, against carbon tetrachloride-induced liver injury. METHODS： A liver injury model was induced by carbon tetrachloride. Cytotoxicity was measured by MTY assay. The activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined with an automatic multifunction-biochemical analyzer and the levels of superoxide dismutase （SOD） and TNF-α were determined following the instructions of SOD kit and TNF radioimmunoassay kit. Uver sections were stained with hematoxylin and eosin （H＆E） for histological evaluation and examined under light microscope. RESULTS： We found that GLPG can alleviate the L-02 liver cells injury induced by carbon tetrachloride （CCh） through the measurements of ALT and AST activities and the administration of GLPG to L-02 cells did not display any toxicity. Furthermore, histological analysis of mice liver injury induced by CCh with or without GLPG pretreatment indicated that GLPG can significantly suppress the toxicity induced by CCh in mice liver. We also found that GLPG reduced TNF-α level induced by CCh in the plasma of mice, whereas increased SOD activity in the rat serum. CONCLUSION： GLPG has hepatic protective activity against CCl4 induced injury both in vitro and in vivo. The possible antihepatotoxic mechanisms may be related to the suppression of TNF-α level and the free radical scavenging activity.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...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 mL/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 beta 1 (TGF-beta 1), matrix metalloprotein 9 (MMP-9) and metallopeptidase inhibitor 1 (TIMP-1) was detected by immunohistochemical analysis. Additionally, TGF-beta 1 and alpha-smooth muscle actin (alpha-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-beta 1, 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-beta 1 and alpha-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 evaluate the hepatoprotective roles of （Z）- 5-（4-methoxybenzylidene）thiazolidine-2,4-dione （SKLB010） against carbon tetrachloride （CCI4）-induced acute and chronic liver injury and its underlying mecha...AIM： To evaluate the hepatoprotective roles of （Z）- 5-（4-methoxybenzylidene）thiazolidine-2,4-dione （SKLB010） against carbon tetrachloride （CCI4）-induced acute and chronic liver injury and its underlying mecha- nisms of action.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
AIM： To investigate the effects of Reishi mushroom, Ganoderma lucidum extract （GLE）, on liver fibrosis induced by carbon tetrachloride （CCl4） in rats. METHODS： Rat hepatic fibrosis was induced by CCl4. Forty Wis...AIM： To investigate the effects of Reishi mushroom, Ganoderma lucidum extract （GLE）, on liver fibrosis induced by carbon tetrachloride （CCl4） in rats. METHODS： Rat hepatic fibrosis was induced by CCl4. Forty Wistar rats were divided randomly into 4 groups： control, CCl4, and two GLE groups. Except for rats in control group, all rats were administered orally with CCl4 （20%, 0.2 mL/100 g body weight） twice a week for 8 weeks. Rats in GLE groups were treated daily with GLE （1 600 or 600 mg/kg） via gastrogavage throughout the whole experimental period. Liver function parameters, such as ALT, AST, albumin, and albumin/globulin （A/G） ratio, spleen weight and hepatic amounts of protein, malondiladehyde （MDA） and hydroxyproline （HP） were determined. Histochemical staining of Sirius red was performed. Expression of transforming growth factor β1 （TGF-β1）, methionine adenosyltransferase （MAT1） 1A and MAT2A mRNA were detected by using RT-PCR. RESULTS： CCl4 caused liver fibrosis, featuring increase in plasma transaminases, hepatic MDA and HP contents, and spleen weight; and decrease in plasma albumin, A/G ratio and hepatic protein level. Compared with CCl4 group, GLE （600, 1 600 mg/kg） treatment significantly increased plasma albumin level and A/G ratio （P〈0.05） and reduced the hepatic HP content （P〈0.01）. GLE （1 600 mg/kg） treatment markedly decreased the activities of transaminases （P〈 0.05）, spleen weight （P〈 0.05） and hepatic MDA content （P〈0.05）; but increased hepatic protein level （P〈0.05）. Liver histology in the GLE （1 600 mg/kg）-treated rats was also improved （P〈0.01）. RT-PCR analysis showed that GLE treatment decreased the expression of TGF-β1 （P〈 0.05-0.001） and changed the expression of MAT1A （P〈0.05-0.01） and MAT2A （P〈 0.05-0.001）. CONCLUSION： Oral administration of GLE significantly reduces CCl4-induced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular necrosis by its free-radical scavenging ability.展开更多
AIM： To investigate the effects of filtrate of fermented mycelia from Antrodia camphorata （FMAC） on liver fibrosis induced by carbon tetrachloride （CCI4） in rats. METHODS： Forty Wistar rats were divided randomly...AIM： To investigate the effects of filtrate of fermented mycelia from Antrodia camphorata （FMAC） on liver fibrosis induced by carbon tetrachloride （CCI4） in rats. METHODS： Forty Wistar rats were divided randomly into control group and model group. All model rats were given 200 mL/L CCI4 （2 mL/Kg, po） twice a week for 8 wk. Four weeks after CCh treatment, thirty model rats were further divided randomly into 3 subgroups： CCh and two FMAC subgroups. Rats in CCI4 and 2 FMAC subgroups were treated with FMAC 0, 0.5 and 1.0 g/kg, daily via gastrogavage beginning at the fitch week and the end of the eighth week. Spleen weight, blood synthetic markers （albumin and prothrombin time） and hepatic malondialdehyde （MDA） and hydroxyproline （HP） concentrations were determined. Expression of collagen I, tissue inhibitor of metalloproteinases （TIMP）-1 and transforming growth factor β1 （TGF-β1） mRNA were detected by RTPCR. Histochemical staining of Masson＇s trichrome was performed. RESULTS： CCI4 caused liver fibrosis, featuring increased prothrombin time, hepatic MDA and HP contents, and spleen weight and decreased plasma albumin level. Compared with CCh subgroup, FMAC subgroup （1 g/kg） significantly decreased the prothrombin time （36.7±7.2 and 25.1±10.2 in CCh and FMAC groups, respectively, P〈 0.05） and increased plasma albumin concentration （22.7± 1.0 and 30.7±2.5 in CCk and FMAC groups, respectively, P 〈 0.05）. Spleen weight was significantly lower in rats treated with CCh and FMAC （1 g/kg） compared to CCh treated rats only （2.7±0.1 and 2.4±0.2 in CCk and FMAC groups, respectively, P〈0.05）. The amounts of hepatic MDA and HP in CCI4± FAMC （1 g/kg） subgroup were also lower thanthose in CCh subgroup （MDA： 3.9±0.1 and 2.4±0.6 in CCh and CCI4 ＋ FMAC groups, respectively, P〈 0.01; HP： 1730.7±258.0 and 1311.5±238.8 in CCI4 and CCI4＋FMAC groups, respectively, P〈0.01）. Histologic examinations showed that CCI4＋FMAC subgroups had thinner or less fibrotic septa than CCh group. RT-PCR analysis indicated that FMAC （1 g/kg） reduced mRNA levels of collagen I, TIMP-1 and TGF-β1 （collagen I： 5.63±2.08 and 1.78±0.48 in CCh and CCI4＋FMAC groups, respectively, P〈0.01; TIMP-1： 1.70±0.82 and 0.34±0.02 in CCh and CCI4 ＋ FMAC groups, respectively, P〈0.01; TGF-β1：38.03±11.9 and 4.26±2.17 in CCh and CCI4＋FMAC groups, respectively, P〈0.01） in the CCI4-treated liver. CONCLUSION： It demonstrates that FMAC can retard the progression of liver fibrosis induced by CCh in rats.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 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
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
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
基金Supported by The Panzhihua Science and Technology Planning Project of China,No.2023ZD-S-57.
文摘BACKGROUND C23,an oligo-peptide derived from cold-inducible RNA-binding protein(CIRP),has been reported to inhibit tissue inflammation,apoptosis and fibrosis by binding to the CIRP receptor;however,there are few reports on its role in liver fibrosis and the underlying mechanism is unknown.AIM To explore whether C23 plays a significant role in carbon tetrachloride(CCl4)-induced liver fibrosis.METHODS CCl4 was injected for 6 weeks to induce liver fibrosis and C23 was used beginning in the second week.Masson and Sirius red staining were used to examine changes in fiber levels.Inflammatory factors in the liver were detected and changes inα-smooth muscle actin(α-SMA)and collagen I expression were detected via immu-nohistochemical staining to evaluate the activation of hematopoietic stellate cells(HSCs).Western blotting was used to detect the activation status of the trans-forming growth factor-beta(TGF-β)/Smad3 axis after C23 treatment.RESULTS CCl4 successfully induced liver fibrosis in mice,while tumor necrosis factor-alpha(TNF-α),IL(interleukin)-1β,and IL-6 levels increased significantly and the IL-10 level decreased significantly.Interestingly,C23 inhibited this process.On the other hand,C23 significantly inhibited the activation of HSCs induced by CCl4,which inhibited the expression ofα-SMA and the synthesis of collagen I.In terms of mechanism,C23 can block Smad3 phosphorylation significantly and inhibits INTRODUCTION At present there is no specific and effective drug for treating liver fibrosis caused by acute or chronic injury.Although preclinical research has made breakthroughs,their suitability as clinical treatments is still unknown.The activation of hepatic stellate cells(HSCs)caused by chronic inflammation is a key process in the development of liver fibrosis and activated HSCs expressα-smooth muscle actin(α-SMA)and transdifferentiate into myofibroblasts with proliferation,migration and secretion abilities,synthesizing the extracellular matrix to deposit in the hepatocyte space and subse-quently forming liver fibrosis[1].Although therapeutic strategies have improved due to past few efforts there is no ideal treatment for hepatic fibrosis[2].Extracellular cold inducible RNA binding protein(CIRP)has been shown to play a role in various acute and chronic inflammatory diseases by promoting tissue inflammation and apoptosis and inducing fibrosis through its receptor Toll-like receptor 4(TLR4)[3].C23 is a recognized competitive inhibitor of CIRP that can competitively bind to CIRP receptors and reduce tissue damage in inflammatory diseases[4].C23 has been shown to significantly reduce serum tumor necrosis factor-alpha(TNF-α),IL(interleukin)-6 and IL-1βlevels.In addition,it can reduce tissue TLR4,TNF-α,IL-6 and IL-1βlevels and inhibit the colocalization of CIRP and TLR4,which plays a significant role in systemic inflammation[5].Re-search has shown that CIRP induces the inflammatory phenotype of lung fibroblasts in a TLR4-dependent manner[6].On the other hand,CIRP is associated with markers of fibrosis andα-SMA is significantly positively correlated with CIRP.Cirp-/-mice exhibit attenuated expression ofα-SMA and collagen(COL1A1 and COL3A1),decreased hydroxyproline content,decreased histological fibrosis scores,and improved pulmonary hypertension[7].C23 inhibited the release of TNF-α,the degradation of IκB and the nuclear translocation of NF-κB in CIRP-stimulated macrophages in a dose-dependent manner and C23 treatment significantly increased the serum levels of lactic dehydrogenase,alanine ami-notransferase,IL-6,TNF-αand IL-1βin septic CLP mice[8].Based on previous research we hypothesized that C23 might alleviate liver fibrosis by inhibiting acute and chronic inflammation.As a selective hepatotoxic chemical carbon tetrachloride(CCl4).can induce inflammation and activate HSCs,promoting liver fibrosis.This study reveals the role and mechanism of C23 in CCl4-induced liver fibrosis in mice.at room temperature for 30 minutes.The gray value of each group was calculated after chemiluminescence.
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.
文摘As an essential amino acid, lysine boosts protein synthesis (Nestor et al1997). Yao et al demonstrated that, lysine also exerts protective effect against the isch-emiclesion of brain. Meanwhile, vitamin C is a natural antioxidant, which has undisputable protectiveaction against free radical damages. In order to ascertain whether their combination could affordbetter effect, we have investigated the prophylactic effect of the couplant ascorbate-lysine inliver injuries.
基金Project supported by the Hi-Tech Research and Development Program(863) of China (No. 2002AA601270)
文摘The dectrochemical reduction characteristics of carbon tetrachlofide （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 mg/L was reduced to trichloromethane and dichloromethane in 2.25 h when 100 g of scrap iron with Fe/Cu ratio of 10：1 （w/w） 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 different. The degradation rate was not significantly influenced 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.
文摘AIM： To develop a simplified and quick protocol to induce cirrhosis and standardize models of partial liver resection in rats. METHODS： In Fischer F344 rats two modified protocols of phenobarbital-carbon tetrachloride （CCl4） （dilution 50%） gavage to induce cirrhosis （frequency adjusted according to weight, but each subsequent dose was systematically administered） were tested, i.e. the rapid and slow protocols. Prothrombin time （PT） and total bilirubin （TB） were also evaluated. Animals from the rapid group underwent 15% hepatectomy and animals from the slow group underwent 70% hepatectomy. RESULTS： Rapid protocol： This corresponded to 1 gavage/4 d over 6 wk （mortality 30%）. Mean PT was 35.2 ±2.8 s （normal： ld.5 s）, and mean TB was 1.8 ± 0.2 mg/dL （normal： 0.1 mg/dL）. Slow protocol： This cop responded to 1 gavage/6 d over 9 wk （mortality 10%）. Mean PT was 11.8 ± 0.2 s （normal： 14.5 s）, and mean TB was 0.4 ± 0.04 mg/dL （normal： 0.1 mg/dL）. Pathological analyses were performed in both protocols which showed persistent cirrhosis at 3 mo. Rat mortality in the rapid garage group who underwent 15% hepatectomy and in the slow garage group who underwent 70% hepatectomy was 50% and 70%, respectively, CONCLUSION： Our modified model is a simplified method to induce cirrhosis which is rapid （6 to 9 wk）, efficient and stable up to 3 mo. Using this method, ＂Child Pugh A＂ or ＂Child Pugh BC＂ cirrhotic rats were obtained. Our models of cirrhosis and hepatectomy can be used in various situations focusing on postoperative survival.
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 a grant from the Institute of Virology, College of Life Sciences, Wuhan University
文摘AIM： To investigate the possible mechanism of the protective effects of a bioactive fraction, Ganoderma lucidum proteoglycan （GLPG）isolated from Ganoderma luddum mycelia, against carbon tetrachloride-induced liver injury. METHODS： A liver injury model was induced by carbon tetrachloride. Cytotoxicity was measured by MTY assay. The activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined with an automatic multifunction-biochemical analyzer and the levels of superoxide dismutase （SOD） and TNF-α were determined following the instructions of SOD kit and TNF radioimmunoassay kit. Uver sections were stained with hematoxylin and eosin （H＆E） for histological evaluation and examined under light microscope. RESULTS： We found that GLPG can alleviate the L-02 liver cells injury induced by carbon tetrachloride （CCh） through the measurements of ALT and AST activities and the administration of GLPG to L-02 cells did not display any toxicity. Furthermore, histological analysis of mice liver injury induced by CCh with or without GLPG pretreatment indicated that GLPG can significantly suppress the toxicity induced by CCh in mice liver. We also found that GLPG reduced TNF-α level induced by CCh in the plasma of mice, whereas increased SOD activity in the rat serum. CONCLUSION： GLPG has hepatic protective activity against CCl4 induced injury both in vitro and in vivo. The possible antihepatotoxic mechanisms may be related to the suppression of TNF-α level and the free radical scavenging activity.
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 mL/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 beta 1 (TGF-beta 1), matrix metalloprotein 9 (MMP-9) and metallopeptidase inhibitor 1 (TIMP-1) was detected by immunohistochemical analysis. Additionally, TGF-beta 1 and alpha-smooth muscle actin (alpha-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-beta 1, 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-beta 1 and alpha-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 National Natural Science Foundation of China and National Key Technologies R and D Program of the 11th five-year plan,No.2009ZX09501-015
文摘AIM： To evaluate the hepatoprotective roles of （Z）- 5-（4-methoxybenzylidene）thiazolidine-2,4-dione （SKLB010） against carbon tetrachloride （CCI4）-induced acute and chronic liver injury and its underlying mecha- nisms of action.
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.
文摘AIM： To investigate the effects of Reishi mushroom, Ganoderma lucidum extract （GLE）, on liver fibrosis induced by carbon tetrachloride （CCl4） in rats. METHODS： Rat hepatic fibrosis was induced by CCl4. Forty Wistar rats were divided randomly into 4 groups： control, CCl4, and two GLE groups. Except for rats in control group, all rats were administered orally with CCl4 （20%, 0.2 mL/100 g body weight） twice a week for 8 weeks. Rats in GLE groups were treated daily with GLE （1 600 or 600 mg/kg） via gastrogavage throughout the whole experimental period. Liver function parameters, such as ALT, AST, albumin, and albumin/globulin （A/G） ratio, spleen weight and hepatic amounts of protein, malondiladehyde （MDA） and hydroxyproline （HP） were determined. Histochemical staining of Sirius red was performed. Expression of transforming growth factor β1 （TGF-β1）, methionine adenosyltransferase （MAT1） 1A and MAT2A mRNA were detected by using RT-PCR. RESULTS： CCl4 caused liver fibrosis, featuring increase in plasma transaminases, hepatic MDA and HP contents, and spleen weight; and decrease in plasma albumin, A/G ratio and hepatic protein level. Compared with CCl4 group, GLE （600, 1 600 mg/kg） treatment significantly increased plasma albumin level and A/G ratio （P〈0.05） and reduced the hepatic HP content （P〈0.01）. GLE （1 600 mg/kg） treatment markedly decreased the activities of transaminases （P〈 0.05）, spleen weight （P〈 0.05） and hepatic MDA content （P〈0.05）; but increased hepatic protein level （P〈0.05）. Liver histology in the GLE （1 600 mg/kg）-treated rats was also improved （P〈0.01）. RT-PCR analysis showed that GLE treatment decreased the expression of TGF-β1 （P〈 0.05-0.001） and changed the expression of MAT1A （P〈0.05-0.01） and MAT2A （P〈 0.05-0.001）. CONCLUSION： Oral administration of GLE significantly reduces CCl4-induced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular necrosis by its free-radical scavenging ability.
基金Supported by Department of Health, Executive Yuan of our country, No. DOH90-TD-1027
文摘AIM： To investigate the effects of filtrate of fermented mycelia from Antrodia camphorata （FMAC） on liver fibrosis induced by carbon tetrachloride （CCI4） in rats. METHODS： Forty Wistar rats were divided randomly into control group and model group. All model rats were given 200 mL/L CCI4 （2 mL/Kg, po） twice a week for 8 wk. Four weeks after CCh treatment, thirty model rats were further divided randomly into 3 subgroups： CCh and two FMAC subgroups. Rats in CCI4 and 2 FMAC subgroups were treated with FMAC 0, 0.5 and 1.0 g/kg, daily via gastrogavage beginning at the fitch week and the end of the eighth week. Spleen weight, blood synthetic markers （albumin and prothrombin time） and hepatic malondialdehyde （MDA） and hydroxyproline （HP） concentrations were determined. Expression of collagen I, tissue inhibitor of metalloproteinases （TIMP）-1 and transforming growth factor β1 （TGF-β1） mRNA were detected by RTPCR. Histochemical staining of Masson＇s trichrome was performed. RESULTS： CCI4 caused liver fibrosis, featuring increased prothrombin time, hepatic MDA and HP contents, and spleen weight and decreased plasma albumin level. Compared with CCh subgroup, FMAC subgroup （1 g/kg） significantly decreased the prothrombin time （36.7±7.2 and 25.1±10.2 in CCh and FMAC groups, respectively, P〈 0.05） and increased plasma albumin concentration （22.7± 1.0 and 30.7±2.5 in CCk and FMAC groups, respectively, P 〈 0.05）. Spleen weight was significantly lower in rats treated with CCh and FMAC （1 g/kg） compared to CCh treated rats only （2.7±0.1 and 2.4±0.2 in CCk and FMAC groups, respectively, P〈0.05）. The amounts of hepatic MDA and HP in CCI4± FAMC （1 g/kg） subgroup were also lower thanthose in CCh subgroup （MDA： 3.9±0.1 and 2.4±0.6 in CCh and CCI4 ＋ FMAC groups, respectively, P〈 0.01; HP： 1730.7±258.0 and 1311.5±238.8 in CCI4 and CCI4＋FMAC groups, respectively, P〈0.01）. Histologic examinations showed that CCI4＋FMAC subgroups had thinner or less fibrotic septa than CCh group. RT-PCR analysis indicated that FMAC （1 g/kg） reduced mRNA levels of collagen I, TIMP-1 and TGF-β1 （collagen I： 5.63±2.08 and 1.78±0.48 in CCh and CCI4＋FMAC groups, respectively, P〈0.01; TIMP-1： 1.70±0.82 and 0.34±0.02 in CCh and CCI4 ＋ FMAC groups, respectively, P〈0.01; TGF-β1：38.03±11.9 and 4.26±2.17 in CCh and CCI4＋FMAC groups, respectively, P〈0.01） in the CCI4-treated liver. CONCLUSION： It demonstrates that FMAC can retard the progression of liver fibrosis induced by CCh in rats.
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.
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.
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.
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.
