[Objectives]To investigate the acute toxicity and hepatoprotective effect of Jinchuan formula plum wine extract on mice,determine its safety range,and evaluate its hepatoprotective effect.[Methods]The median lethal do...[Objectives]To investigate the acute toxicity and hepatoprotective effect of Jinchuan formula plum wine extract on mice,determine its safety range,and evaluate its hepatoprotective effect.[Methods]The median lethal dose(LD_(50))was determined by acute toxicity test with the toxic reaction and mortality of mice as indexes.Sixty Kunming mice were randomly divided into 6 groups:normal control group,model group(ConA-induced liver injury model),Jinchuan formula plum wine high,medium and low dose groups(1.0,0.5,0.25 g/kg)and silybin group(0.1 g/kg).The levels of ALT,AST,LDH in serum and TG,VLDL in liver were measured.After HE staining,the pathological changes of liver tissue in mice were observed,and the liver protective effect of Jinchuan formula plum wine extract was analyzed and evaluated.[Results]LD_(50)was 11.18 g/kg,and the 95%confidence limit of LD_(50)was 10.31-12.05 g/kg.The high-dose group of Jinchuan formula plum wine extract could significantly reduce the serum ALT and AST activities of ConA-induced liver injury mice(P<0.05).[Conclusions]Jinchuan formula plum wine extract is relatively safe,and also has a protective effect on liver injury.展开更多
We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuv...We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuvastatin has a greater potential compared with other statins to damage the liver is unclear and the involved mechanisms are also unknown. However, rosuvastatin is taken up by hepatocytes more selectively and more efficiently than other statins, and this may reasonably represent an important variable to explain the hepatotoxic potential of rosuvastatin. Our report supports the view that a clinically significant risk of liver toxicity should be considered even when rosuvastatin is given at the range of doses used in common clinical practice.展开更多
Dietary supplements represent an increasingly common source of drug-induced liver injury. Hydroxycut is a popular weight loss supplement which has previously been linked to hepatotoxicity, although the individual chem...Dietary supplements represent an increasingly common source of drug-induced liver injury. Hydroxycut is a popular weight loss supplement which has previously been linked to hepatotoxicity, although the individual chemical components underlying liver injury remain poorly understood. We report two cases of acute hepatitis in the setting of Hydroxycut exposure and describe possible mechanisms of liver injury. We also comprehensively review and summarize the existing literature on commonly used weight loss supplements, and their individual components which have demon-strated potential for liver toxicity. An increased effort to screen for and educate patients and physicians about supplement-associated hepatotoxicity is warranted.展开更多
Therapeutic experiments are commonly performed on laboratory animals to inves-tigate the possible mechanism(s)of action of toxic agents as well as drugs or sub-stances under consideration.The use of toxins in laborato...Therapeutic experiments are commonly performed on laboratory animals to inves-tigate the possible mechanism(s)of action of toxic agents as well as drugs or sub-stances under consideration.The use of toxins in laboratory animal models,including rats,is intended to cause toxicity.This study aimed to investigate different models of hepatotoxicity and nephrotoxicity in laboratory animals to help researchers advance their research goals.The current narrative review used databases such as Medline,Web of Science,Scopus,and Embase and appropriate keywords until June 2021.Nephrotoxicity and hepatotoxicity models derived from some toxic agents such as cisplatin,acetaminophen,doxorubicin,some anticancer drugs,and other materials through various signaling pathways are investigated.To understand the models of renal or hepatotoxicity in laboratory animals,we have provided a list of toxic agents and their toxicity procedures in this review.展开更多
Propylthiouracyl (PTU)-related liver toxicity is likely to oc- cur in about 1% of treated patients. In case of acute or subacute hepatitis, liver failure may occur in about one third. We report two further cases of PT...Propylthiouracyl (PTU)-related liver toxicity is likely to oc- cur in about 1% of treated patients. In case of acute or subacute hepatitis, liver failure may occur in about one third. We report two further cases of PTU-induced sub- acute hepatitis, in whom the delay between occurrence of liver damage after the initiation of treatment, the un- derestimation of its severity and the delayed withdrawal of the drug were all likely responsible for liver failure. The high incidence of liver toxicity related to PTU, its potential severity and delayed occurrence after initiation of treatment are in favor of monthly alanine aminotrans- ferase monitoring, at least during the first six months of therapy.展开更多
The liver is the organ by which the majority of sub-stances are metabolized, including psychotropic drugs. There are several pharmacokinetic changes in end-stage liver disease that can interfere with the metabolizatio...The liver is the organ by which the majority of sub-stances are metabolized, including psychotropic drugs. There are several pharmacokinetic changes in end-stage liver disease that can interfere with the metabolization of psychotropic drugs. This fact is particularly true in drugs with extensive first--pass metabolism, highly protein bound drugs and drugs depending on phase I hepatic metabolic reactions. Psychopharmacological agents are also associated with a risk of hepatotoxicity. The evidence is insufficient for definite conclusions regarding the prevalence and severity of psychiatric drug-induced liver injury. High-risk psychotropics are not advised when there is pre-existing liver disease, and after starting a psychotropic agent in a patient with hepatic impairment, frequent liver function/lesion monitoring is advised. The authors carefully review the pharmacokinetic disturbances induced by end-stage liver disease and the potential of psychopharmacological agents for liver toxicity.展开更多
Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality worldwide.However,there are currently no effective anti-fibrotic therapies available,especiall...Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality worldwide.However,there are currently no effective anti-fibrotic therapies available,especially for latestage patients,which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cellspecific responses in different fibrosis stages.To reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes,we generated a single-nucleus transcriptomic atlas encompassing 49919nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride(CCl_(4))-induced progressive liver fibrosis.Integrative analysis distinguished the sequential responses to injury of hepatocytes,hepatic stellate cells and endothelial cells.Moreover,we reconstructed the cell-cell interactions and gene regulatory networks implicated in these processes.These integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions,dysfunction for clearance by apoptosis of activated hepatic stellate cells,accumulation of pro-fibrotic signals,and the switch from an anti-angiogenic to a pro-angiogenic program during CCl_(4)-induced progressive liver fibrosis.Our dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.展开更多
Introduction: Human immunodeficiency virus (HIV) infection is a public health problem of concern. Anti-retroviral therapy (ART) is associated with multiple side effects. This study aimed at identifying the different h...Introduction: Human immunodeficiency virus (HIV) infection is a public health problem of concern. Anti-retroviral therapy (ART) is associated with multiple side effects. This study aimed at identifying the different hepatic manifestations of antiretroviral therapy and the responsible molecules. Patients and Methods: This was an eight months period prospective descriptive study, from January 1st to August 31st, 2015, conducted in the Department of Gastroenterology and Internal Medicine at the Brazzaville University Teaching Hospital. Study participants were treatment-na?ve HIV patients who were initiated on ART treatment during the study period. Patients with liver disease, liver cytolysis prior to initiation of therapy, and those with alternative therapy that may cause hepatotoxicity were excluded. The sample size was 110 patients. Results: The age was ranging from 25 to 70 years with a mean age of 47.5 ± 7.5 years. During the six months of follow-up, the alarming hepatic signs were observed in 26.36% of cases (n = 29) in the 3rd month of treatment. There was no observed alarming sign in the 6th month of follow-up. The cytolytic pattern was observed in 54.55% of cases (n = 60) in the 3rd month. The cholestatic pattern was observed in 6.36% of cases (n = 7) in the 3rd month. Triple therapy combination of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most used in 57.27% (n = 63) with a statistically significant p value to the occurrence of cytolytic pattern (p Conclusion: Drug induced liver toxicity occurs in a significant number of patients starting ART. The prevalence of hepatic events was high at the third month of treatment and the triple therapy of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most incriminated.展开更多
Liver injury is a common cause of drug approval withdrawal during drug development,pre-clinical research,and clinical treatment.If not properly treated,patients with severe liver injury can suffer from acute liver fai...Liver injury is a common cause of drug approval withdrawal during drug development,pre-clinical research,and clinical treatment.If not properly treated,patients with severe liver injury can suffer from acute liver failure or even death.Thus,utilization of the convenient in vitro hepatotoxicity assessment model for early detection of drug-induced hepatotoxicity is vital for drug development and safe personalized medication.Biomaterials(e.g.,hydrogels,nanofibers,decellularized liver matrix)and bioengineering technologies(e.g.,microarrays,micropatterns,3D printing,and microfluidics)have been applied for in vitro hepatotoxicity assessment models.This review summarizes the structure and functions of the liver as well as the components of in vitro hepatotoxicity assessment models.In addition,it highlights the latest advances in developing hepatotoxicity models with the ultimate goal of further clinical translation.展开更多
BACKGROUND Bisphenol A(BPA)is present in many plastic products and food packaging.On the other hand,fertaric acid(FA)is a hydroxycinnamic acid.AIM To investigate the effect of FA on BPA-related liver,kidney,and testis...BACKGROUND Bisphenol A(BPA)is present in many plastic products and food packaging.On the other hand,fertaric acid(FA)is a hydroxycinnamic acid.AIM To investigate the effect of FA on BPA-related liver,kidney,and testis toxicity,DNA breakdown,and histopathology in male rats.METHODS Thirty male albino rats were divided into five equal groups(6 rats/group):Control,paraffin oil,FA-,BPA-,and FA+BPA-treated groups.The control and paraffin oil groups were administered orally with 1 mL distilled water and 1 mL paraffin oil,respectively.The FA-,BPA-,and FA+BPA-treated groups were administered orally with FA(45 mg/kg,bw)dissolved in 1 mL distilled water,BPA(4 mg/kg,bw)dissolved in 1 mL paraffin oil,and FA(45 mg/kg,bw)followed by BPA(4 mg/kg,bw),respectively.All these treatments were given once a day for 6 wk.RESULTS BPA induced a significant decrease in serum alkaline phosphatase,acid phosphatase,sodium,potassium and chloride,testosterone,dehydroepiandrosterone sulfate,glucose-6-phosphate dehydrogenase,3β-hydroxysteroid dehydrogenase,and testis protein levels but a highly significant increase in serum aspartate aminotransferase,alanine aminotransferase,γ-glutamyl transpeptidase,lactate dehydrogenase,bilirubin,urea,creatinine,uric acid,luteinizing hormone,follicle stimulating hormone,sex hormone binding globulin,blood urea nitrogen,and testis cholesterol levels.Also,FA inhibited the degradation of liver,kidney,and testis DNA content.Oral administration of FA to BPA-treated rats restored all the above parameters to normal levels.CONCLUSION FA ameliorates BPA-induced liver,kidney,and testis toxicity,DNA breakdown,and histopathological changes.展开更多
Aim: To evaluate chronic exposure of carmoisine at ADI doses on some hepatocellular and renal parameters of male and female albino rats as well as to determine sex-dependent toxicity. Study Design: The study involves ...Aim: To evaluate chronic exposure of carmoisine at ADI doses on some hepatocellular and renal parameters of male and female albino rats as well as to determine sex-dependent toxicity. Study Design: The study involves treatment for 30, 60, and 90 days. Each phase consists of 40 rats, divided into treatment and control groups. The treated groups were orally administered with 4.0 mg/kg of carmoisine daily for the periods of 30, 60, and 90 days. Methodology: At the end of the treatment, the rats were allowed to fast for 18 hours followed by the collection of 5 ml of whole blood specimens by means of cardiac puncture into Lithium Heparin bottles and fluoride oxalate bottles (for glucose only). Plasma obtained was analyzed for glucose (GLU), AST, ALT, ALP, creatinine (CRT), and urea. Hepatic and Renal tissues collected were fixed in 10% formol saline and later examined histologically using H&E stain. Statistical data analysis was done using GraphPad Prism version 9.02. Results: Glucose indicated significant increases after 30, 60, and 90 days of chronic treatment at ADI doses. Urea, Creatinine, AST, ALT and ALP showed significantly higher values after 60 and 90 days of treatment (except creatinine in male rats and ALP in female rats after 60 and 90 days respectively). Hepatic distortions, vacuolation, compression of central vein were seen in the liver section while distortion of proximal and distal tubules, and inflammation of the glomerulus were observed in the renal tissue of the treated rats. Conclusion: The administration of camoisine over a period of 30 days at ADI dose did not indicate hepatocellullar and renal derangements as well histological distortions in liver, and kidneys. However, after 60 and 90 days, mild hepatocellular, and renal derangements were seen. No sex-dependent toxicity was observed.展开更多
AIM:To investigate anxiety and depression propensities in patients with toxic liver injury.METHODS:The subjects were divided into three groups:a healthy control group(Group 1,n=125),an acute non-toxic liver injury gro...AIM:To investigate anxiety and depression propensities in patients with toxic liver injury.METHODS:The subjects were divided into three groups:a healthy control group(Group 1,n=125),an acute non-toxic liver injury group(Group 2,n=124),and a group with acute toxic liver injury group caused by noncommercial herbal preparations(Group 3,n=126).These three groups were compared and evaluated through questionnaire surveys and using the Hospital Anxiety-Depression Scale(HADS),Beck Anxiety Inventory(BAI),Beck Depression Inventory(BDI),and the hypochondriasis scale.RESULTS:The HADS anxiety subscale was 4.9±2.7,5.0±3.0 and 5.6±3.4,in Groups 1,2,and 3,respectively.The HADS depression subscale in Group 3 showed the most significant score(5.2±3.2,6.4±3.4 and 7.2±3.4in Groups 1,2,and 3,respectively)(P<0.01 vs Group 1,P<0.05 vs Group 2).The BAI and BDI in Group 3showed the most significant score(7.0±6.3 and 6.9±6.9,9.5±8.6 and 8.8±7.3,10.7±7.2 and 11.6±8.5in Groups 1,2,and 3,respectively)(BAI:P<0.01 vs Group 1,P<0.05 vs Group 2)(BDI:P<0.01 vs Group1 and 2).Group 3 showed a significantly higher hypochondriasis score(8.2±6.0,11.6±7.5 and 13.1±6.5in Groups 1,2,and 3,respectively)(P<0.01 vs Group 1,P<0.05 vs Group 2).CONCLUSION:Psychological factors that present vulnerability to the temptation to use alternative medicines,such as herbs and plant preparations,are important for understanding toxic liver injury.展开更多
Objective:To investigate the protective potential of ethanolic extracts of Tetracera scandens L.(T.scandens) against CCl_4 induced oxidative stress in liver tissues.Methods:Dried leaf powder of T.scandens was extracte...Objective:To investigate the protective potential of ethanolic extracts of Tetracera scandens L.(T.scandens) against CCl_4 induced oxidative stress in liver tissues.Methods:Dried leaf powder of T.scandens was extracted with ethanol and concentrated to yield a dry residue.Rats were administered with 100 mg/kg of ethanolic extracts orally once daily for one week.Animals were subsequently administered with a single dose of CCl_4(I mL/kg body weight,intraperitoneal injection).Various assays,such as serum levels of alanine aminotransferase,aspartate aminotransferase,lipid peroxidation,protein oxidation(carbonyl protein group),tumor necrosis factor alpha,catalase,superoxide dismutase,and glutathione peroxidase,were used to assess damage caused by CCl_4 and the protective effects of the ethanol extract on liver tissues.Results:Hepatotoxicity induced by CCl_4 was evidenced by a significant increase in serum aspartate aminotransferase and alanine aminotransferase level,lipid peroxidation,protein carbonyl group,and tumor necrosis factor alpha,as well as decreased activity of the hepatic antioxidant enzymes(catalase.superoxide dismutase.and glutathione peroxidase).Treatment with ethanolic T.scandens extracts prevented all of these typically observed changes in CCl_4-treated rats.Conclusions:Our findings indicate that T.scandens has a significant protective effect against CCl_4 induced hepatotoxicity in rat.which may be due to its antioxidant properties.展开更多
The discovery of induced pluripotent stem cells (iPSCs) unraveled a mystery in stem cell research, after identification of four re-programming factors for generating pluripotent stem cells without the need of embryos....The discovery of induced pluripotent stem cells (iPSCs) unraveled a mystery in stem cell research, after identification of four re-programming factors for generating pluripotent stem cells without the need of embryos. This breakthrough in generating iPSCs from somatic cells has overcome the ethical issues and immune rejection involved in the use of human embryonic stem cells. Hence, iPSCs form a great potential source for developing disease models, drug toxicity screening and cell-based therapies. These cells have the potential to differentiate into desired cell types, including hepatocytes, under in vitro as well as under in vivo conditions given the proper microenvironment. iPSC-derived hepatocytes could be useful as an unlimited source, which can be utilized in disease modeling, drug toxicity testing and producing autologous cell therapies that would avoid immune rejection and enable correction of gene defects prior to cell transplantation. In this review, we discuss the induction methods, role of reprogramming factors, and characterization of iPSCs, along with hepatocyte differentiation from iPSCs and potential applications. Further, we discuss the location and detection of liver stem cells and their role in liver regeneration. Although tumor formation and genetic mutations are a cause of concern, iPSCs still form a promising source for clinical applications.展开更多
BACKGROUND： Acute poisoning （AP） may cause failure of the liver and kidney, and evendeath. This study aimed to investigate the efficacy of artificial liver support system （ALSS） on thetreatment of liver failure a...BACKGROUND： Acute poisoning （AP） may cause failure of the liver and kidney, and evendeath. This study aimed to investigate the efficacy of artificial liver support system （ALSS） on thetreatment of liver failure after acute poisoning.METHODS： A total of 31 patients with liver failure caused by AP were admitted to emergency ICU,central ICU, and Department of Gastroenterology from 2005 to 2009 in Zhongshan Hospital Affi liatedto Xiamen University, China. Among them, 13 patients served as a treatment group, and used ALSS inaddition to detoxifi cation treatment and protective treatment of liver function, and the other 18 patientsserved as a control group receiving detoxifi cation treatment and protective treatment of liver function.RESULTS： In the treatment group, 10 patients （76.9%） were cured or improved, 2 died, and1 was discharged against advice. In the 18 patients in the control group, 7 （38.9%） were cured orimproved, 3 died, and 8 were discharged against advice. There was a significant difference in therates of improvement between the two groups （P〈0.05）.CONCLUSION： ALSS is a safe and effective clinical method for the treatment of acute toxicliver failure.展开更多
Right portal vein ligation (PVL) is a safe and widespread procedure to induce controlateral liver hypertrophy for the treatment of bilobar colorectal liver metastases. We report a case of a 60-year-old man treated by ...Right portal vein ligation (PVL) is a safe and widespread procedure to induce controlateral liver hypertrophy for the treatment of bilobar colorectal liver metastases. We report a case of a 60-year-old man treated by both right PVL and ligation of the glissonian branches of segment 4 for colorectal liver metastases surrounding the right and median hepatic veins. After surgery, the patient developed massive hepatic necrosis with secondary pulmonary and renal insufficiency requiring transfer to the intensive care unit. This so-called toxic liver syndrome finally regressed after hemofiltration and positive oxygen therapy. Diagnosis of acute congestion of the ligated lobe was suspected. The mechanism suspected was an increase in arterial inflow secondary to portal vein ligation concomitant with a decrease in venous outflow due to liver metastases encircling the right and median hepatic vein. This is the first documented case of toxic liver syndrome in a non-cirrhotic patient with favorable issue, and a rare complication of PVL.展开更多
文摘[Objectives]To investigate the acute toxicity and hepatoprotective effect of Jinchuan formula plum wine extract on mice,determine its safety range,and evaluate its hepatoprotective effect.[Methods]The median lethal dose(LD_(50))was determined by acute toxicity test with the toxic reaction and mortality of mice as indexes.Sixty Kunming mice were randomly divided into 6 groups:normal control group,model group(ConA-induced liver injury model),Jinchuan formula plum wine high,medium and low dose groups(1.0,0.5,0.25 g/kg)and silybin group(0.1 g/kg).The levels of ALT,AST,LDH in serum and TG,VLDL in liver were measured.After HE staining,the pathological changes of liver tissue in mice were observed,and the liver protective effect of Jinchuan formula plum wine extract was analyzed and evaluated.[Results]LD_(50)was 11.18 g/kg,and the 95%confidence limit of LD_(50)was 10.31-12.05 g/kg.The high-dose group of Jinchuan formula plum wine extract could significantly reduce the serum ALT and AST activities of ConA-induced liver injury mice(P<0.05).[Conclusions]Jinchuan formula plum wine extract is relatively safe,and also has a protective effect on liver injury.
文摘We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuvastatin has a greater potential compared with other statins to damage the liver is unclear and the involved mechanisms are also unknown. However, rosuvastatin is taken up by hepatocytes more selectively and more efficiently than other statins, and this may reasonably represent an important variable to explain the hepatotoxic potential of rosuvastatin. Our report supports the view that a clinically significant risk of liver toxicity should be considered even when rosuvastatin is given at the range of doses used in common clinical practice.
文摘Dietary supplements represent an increasingly common source of drug-induced liver injury. Hydroxycut is a popular weight loss supplement which has previously been linked to hepatotoxicity, although the individual chemical components underlying liver injury remain poorly understood. We report two cases of acute hepatitis in the setting of Hydroxycut exposure and describe possible mechanisms of liver injury. We also comprehensively review and summarize the existing literature on commonly used weight loss supplements, and their individual components which have demon-strated potential for liver toxicity. An increased effort to screen for and educate patients and physicians about supplement-associated hepatotoxicity is warranted.
文摘Therapeutic experiments are commonly performed on laboratory animals to inves-tigate the possible mechanism(s)of action of toxic agents as well as drugs or sub-stances under consideration.The use of toxins in laboratory animal models,including rats,is intended to cause toxicity.This study aimed to investigate different models of hepatotoxicity and nephrotoxicity in laboratory animals to help researchers advance their research goals.The current narrative review used databases such as Medline,Web of Science,Scopus,and Embase and appropriate keywords until June 2021.Nephrotoxicity and hepatotoxicity models derived from some toxic agents such as cisplatin,acetaminophen,doxorubicin,some anticancer drugs,and other materials through various signaling pathways are investigated.To understand the models of renal or hepatotoxicity in laboratory animals,we have provided a list of toxic agents and their toxicity procedures in this review.
文摘Propylthiouracyl (PTU)-related liver toxicity is likely to oc- cur in about 1% of treated patients. In case of acute or subacute hepatitis, liver failure may occur in about one third. We report two further cases of PTU-induced sub- acute hepatitis, in whom the delay between occurrence of liver damage after the initiation of treatment, the un- derestimation of its severity and the delayed withdrawal of the drug were all likely responsible for liver failure. The high incidence of liver toxicity related to PTU, its potential severity and delayed occurrence after initiation of treatment are in favor of monthly alanine aminotrans- ferase monitoring, at least during the first six months of therapy.
文摘The liver is the organ by which the majority of sub-stances are metabolized, including psychotropic drugs. There are several pharmacokinetic changes in end-stage liver disease that can interfere with the metabolization of psychotropic drugs. This fact is particularly true in drugs with extensive first--pass metabolism, highly protein bound drugs and drugs depending on phase I hepatic metabolic reactions. Psychopharmacological agents are also associated with a risk of hepatotoxicity. The evidence is insufficient for definite conclusions regarding the prevalence and severity of psychiatric drug-induced liver injury. High-risk psychotropics are not advised when there is pre-existing liver disease, and after starting a psychotropic agent in a patient with hepatic impairment, frequent liver function/lesion monitoring is advised. The authors carefully review the pharmacokinetic disturbances induced by end-stage liver disease and the potential of psychopharmacological agents for liver toxicity.
基金supported by the National Natural Science Foundation of China(32200688,92068106,U20A2015,32211530050)Guangdong Basic and Applied Basic Research Foundation(2021B1515120075,2021A1515110180)Science and Technology Program of Guangzhou(202201010408,202201011037)。
文摘Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality worldwide.However,there are currently no effective anti-fibrotic therapies available,especially for latestage patients,which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cellspecific responses in different fibrosis stages.To reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes,we generated a single-nucleus transcriptomic atlas encompassing 49919nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride(CCl_(4))-induced progressive liver fibrosis.Integrative analysis distinguished the sequential responses to injury of hepatocytes,hepatic stellate cells and endothelial cells.Moreover,we reconstructed the cell-cell interactions and gene regulatory networks implicated in these processes.These integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions,dysfunction for clearance by apoptosis of activated hepatic stellate cells,accumulation of pro-fibrotic signals,and the switch from an anti-angiogenic to a pro-angiogenic program during CCl_(4)-induced progressive liver fibrosis.Our dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.
文摘Introduction: Human immunodeficiency virus (HIV) infection is a public health problem of concern. Anti-retroviral therapy (ART) is associated with multiple side effects. This study aimed at identifying the different hepatic manifestations of antiretroviral therapy and the responsible molecules. Patients and Methods: This was an eight months period prospective descriptive study, from January 1st to August 31st, 2015, conducted in the Department of Gastroenterology and Internal Medicine at the Brazzaville University Teaching Hospital. Study participants were treatment-na?ve HIV patients who were initiated on ART treatment during the study period. Patients with liver disease, liver cytolysis prior to initiation of therapy, and those with alternative therapy that may cause hepatotoxicity were excluded. The sample size was 110 patients. Results: The age was ranging from 25 to 70 years with a mean age of 47.5 ± 7.5 years. During the six months of follow-up, the alarming hepatic signs were observed in 26.36% of cases (n = 29) in the 3rd month of treatment. There was no observed alarming sign in the 6th month of follow-up. The cytolytic pattern was observed in 54.55% of cases (n = 60) in the 3rd month. The cholestatic pattern was observed in 6.36% of cases (n = 7) in the 3rd month. Triple therapy combination of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most used in 57.27% (n = 63) with a statistically significant p value to the occurrence of cytolytic pattern (p Conclusion: Drug induced liver toxicity occurs in a significant number of patients starting ART. The prevalence of hepatic events was high at the third month of treatment and the triple therapy of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most incriminated.
基金supports from General Program from the National Natural Science Foundation of China(No.31871016)the National Key Research and Development Program(2016YFC1101302)from the Ministry of Science and Technology of China.
文摘Liver injury is a common cause of drug approval withdrawal during drug development,pre-clinical research,and clinical treatment.If not properly treated,patients with severe liver injury can suffer from acute liver failure or even death.Thus,utilization of the convenient in vitro hepatotoxicity assessment model for early detection of drug-induced hepatotoxicity is vital for drug development and safe personalized medication.Biomaterials(e.g.,hydrogels,nanofibers,decellularized liver matrix)and bioengineering technologies(e.g.,microarrays,micropatterns,3D printing,and microfluidics)have been applied for in vitro hepatotoxicity assessment models.This review summarizes the structure and functions of the liver as well as the components of in vitro hepatotoxicity assessment models.In addition,it highlights the latest advances in developing hepatotoxicity models with the ultimate goal of further clinical translation.
文摘BACKGROUND Bisphenol A(BPA)is present in many plastic products and food packaging.On the other hand,fertaric acid(FA)is a hydroxycinnamic acid.AIM To investigate the effect of FA on BPA-related liver,kidney,and testis toxicity,DNA breakdown,and histopathology in male rats.METHODS Thirty male albino rats were divided into five equal groups(6 rats/group):Control,paraffin oil,FA-,BPA-,and FA+BPA-treated groups.The control and paraffin oil groups were administered orally with 1 mL distilled water and 1 mL paraffin oil,respectively.The FA-,BPA-,and FA+BPA-treated groups were administered orally with FA(45 mg/kg,bw)dissolved in 1 mL distilled water,BPA(4 mg/kg,bw)dissolved in 1 mL paraffin oil,and FA(45 mg/kg,bw)followed by BPA(4 mg/kg,bw),respectively.All these treatments were given once a day for 6 wk.RESULTS BPA induced a significant decrease in serum alkaline phosphatase,acid phosphatase,sodium,potassium and chloride,testosterone,dehydroepiandrosterone sulfate,glucose-6-phosphate dehydrogenase,3β-hydroxysteroid dehydrogenase,and testis protein levels but a highly significant increase in serum aspartate aminotransferase,alanine aminotransferase,γ-glutamyl transpeptidase,lactate dehydrogenase,bilirubin,urea,creatinine,uric acid,luteinizing hormone,follicle stimulating hormone,sex hormone binding globulin,blood urea nitrogen,and testis cholesterol levels.Also,FA inhibited the degradation of liver,kidney,and testis DNA content.Oral administration of FA to BPA-treated rats restored all the above parameters to normal levels.CONCLUSION FA ameliorates BPA-induced liver,kidney,and testis toxicity,DNA breakdown,and histopathological changes.
文摘Aim: To evaluate chronic exposure of carmoisine at ADI doses on some hepatocellular and renal parameters of male and female albino rats as well as to determine sex-dependent toxicity. Study Design: The study involves treatment for 30, 60, and 90 days. Each phase consists of 40 rats, divided into treatment and control groups. The treated groups were orally administered with 4.0 mg/kg of carmoisine daily for the periods of 30, 60, and 90 days. Methodology: At the end of the treatment, the rats were allowed to fast for 18 hours followed by the collection of 5 ml of whole blood specimens by means of cardiac puncture into Lithium Heparin bottles and fluoride oxalate bottles (for glucose only). Plasma obtained was analyzed for glucose (GLU), AST, ALT, ALP, creatinine (CRT), and urea. Hepatic and Renal tissues collected were fixed in 10% formol saline and later examined histologically using H&E stain. Statistical data analysis was done using GraphPad Prism version 9.02. Results: Glucose indicated significant increases after 30, 60, and 90 days of chronic treatment at ADI doses. Urea, Creatinine, AST, ALT and ALP showed significantly higher values after 60 and 90 days of treatment (except creatinine in male rats and ALP in female rats after 60 and 90 days respectively). Hepatic distortions, vacuolation, compression of central vein were seen in the liver section while distortion of proximal and distal tubules, and inflammation of the glomerulus were observed in the renal tissue of the treated rats. Conclusion: The administration of camoisine over a period of 30 days at ADI dose did not indicate hepatocellullar and renal derangements as well histological distortions in liver, and kidneys. However, after 60 and 90 days, mild hepatocellular, and renal derangements were seen. No sex-dependent toxicity was observed.
基金Supported by Foundation of the Korean Association for the Study of the Liver Research Grant
文摘AIM:To investigate anxiety and depression propensities in patients with toxic liver injury.METHODS:The subjects were divided into three groups:a healthy control group(Group 1,n=125),an acute non-toxic liver injury group(Group 2,n=124),and a group with acute toxic liver injury group caused by noncommercial herbal preparations(Group 3,n=126).These three groups were compared and evaluated through questionnaire surveys and using the Hospital Anxiety-Depression Scale(HADS),Beck Anxiety Inventory(BAI),Beck Depression Inventory(BDI),and the hypochondriasis scale.RESULTS:The HADS anxiety subscale was 4.9±2.7,5.0±3.0 and 5.6±3.4,in Groups 1,2,and 3,respectively.The HADS depression subscale in Group 3 showed the most significant score(5.2±3.2,6.4±3.4 and 7.2±3.4in Groups 1,2,and 3,respectively)(P<0.01 vs Group 1,P<0.05 vs Group 2).The BAI and BDI in Group 3showed the most significant score(7.0±6.3 and 6.9±6.9,9.5±8.6 and 8.8±7.3,10.7±7.2 and 11.6±8.5in Groups 1,2,and 3,respectively)(BAI:P<0.01 vs Group 1,P<0.05 vs Group 2)(BDI:P<0.01 vs Group1 and 2).Group 3 showed a significantly higher hypochondriasis score(8.2±6.0,11.6±7.5 and 13.1±6.5in Groups 1,2,and 3,respectively)(P<0.01 vs Group 1,P<0.05 vs Group 2).CONCLUSION:Psychological factors that present vulnerability to the temptation to use alternative medicines,such as herbs and plant preparations,are important for understanding toxic liver injury.
基金Supported by the"Program Tay Bac"(Grants number:KHCN-TB05C/13-18)
文摘Objective:To investigate the protective potential of ethanolic extracts of Tetracera scandens L.(T.scandens) against CCl_4 induced oxidative stress in liver tissues.Methods:Dried leaf powder of T.scandens was extracted with ethanol and concentrated to yield a dry residue.Rats were administered with 100 mg/kg of ethanolic extracts orally once daily for one week.Animals were subsequently administered with a single dose of CCl_4(I mL/kg body weight,intraperitoneal injection).Various assays,such as serum levels of alanine aminotransferase,aspartate aminotransferase,lipid peroxidation,protein oxidation(carbonyl protein group),tumor necrosis factor alpha,catalase,superoxide dismutase,and glutathione peroxidase,were used to assess damage caused by CCl_4 and the protective effects of the ethanol extract on liver tissues.Results:Hepatotoxicity induced by CCl_4 was evidenced by a significant increase in serum aspartate aminotransferase and alanine aminotransferase level,lipid peroxidation,protein carbonyl group,and tumor necrosis factor alpha,as well as decreased activity of the hepatic antioxidant enzymes(catalase.superoxide dismutase.and glutathione peroxidase).Treatment with ethanolic T.scandens extracts prevented all of these typically observed changes in CCl_4-treated rats.Conclusions:Our findings indicate that T.scandens has a significant protective effect against CCl_4 induced hepatotoxicity in rat.which may be due to its antioxidant properties.
基金Supported by Asian Healthcare Foundation, Hyderabad, India
文摘The discovery of induced pluripotent stem cells (iPSCs) unraveled a mystery in stem cell research, after identification of four re-programming factors for generating pluripotent stem cells without the need of embryos. This breakthrough in generating iPSCs from somatic cells has overcome the ethical issues and immune rejection involved in the use of human embryonic stem cells. Hence, iPSCs form a great potential source for developing disease models, drug toxicity screening and cell-based therapies. These cells have the potential to differentiate into desired cell types, including hepatocytes, under in vitro as well as under in vivo conditions given the proper microenvironment. iPSC-derived hepatocytes could be useful as an unlimited source, which can be utilized in disease modeling, drug toxicity testing and producing autologous cell therapies that would avoid immune rejection and enable correction of gene defects prior to cell transplantation. In this review, we discuss the induction methods, role of reprogramming factors, and characterization of iPSCs, along with hepatocyte differentiation from iPSCs and potential applications. Further, we discuss the location and detection of liver stem cells and their role in liver regeneration. Although tumor formation and genetic mutations are a cause of concern, iPSCs still form a promising source for clinical applications.
文摘BACKGROUND： Acute poisoning （AP） may cause failure of the liver and kidney, and evendeath. This study aimed to investigate the efficacy of artificial liver support system （ALSS） on thetreatment of liver failure after acute poisoning.METHODS： A total of 31 patients with liver failure caused by AP were admitted to emergency ICU,central ICU, and Department of Gastroenterology from 2005 to 2009 in Zhongshan Hospital Affi liatedto Xiamen University, China. Among them, 13 patients served as a treatment group, and used ALSS inaddition to detoxifi cation treatment and protective treatment of liver function, and the other 18 patientsserved as a control group receiving detoxifi cation treatment and protective treatment of liver function.RESULTS： In the treatment group, 10 patients （76.9%） were cured or improved, 2 died, and1 was discharged against advice. In the 18 patients in the control group, 7 （38.9%） were cured orimproved, 3 died, and 8 were discharged against advice. There was a significant difference in therates of improvement between the two groups （P〈0.05）.CONCLUSION： ALSS is a safe and effective clinical method for the treatment of acute toxicliver failure.
文摘Right portal vein ligation (PVL) is a safe and widespread procedure to induce controlateral liver hypertrophy for the treatment of bilobar colorectal liver metastases. We report a case of a 60-year-old man treated by both right PVL and ligation of the glissonian branches of segment 4 for colorectal liver metastases surrounding the right and median hepatic veins. After surgery, the patient developed massive hepatic necrosis with secondary pulmonary and renal insufficiency requiring transfer to the intensive care unit. This so-called toxic liver syndrome finally regressed after hemofiltration and positive oxygen therapy. Diagnosis of acute congestion of the ligated lobe was suspected. The mechanism suspected was an increase in arterial inflow secondary to portal vein ligation concomitant with a decrease in venous outflow due to liver metastases encircling the right and median hepatic vein. This is the first documented case of toxic liver syndrome in a non-cirrhotic patient with favorable issue, and a rare complication of PVL.
