Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs...Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and Pub Med.展开更多
Objective:To assess the hepatoprotective effect of Solanum xanthocarpum(S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals.Methods:Ethanolic(50%) fruit extract of...Objective:To assess the hepatoprotective effect of Solanum xanthocarpum(S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals.Methods:Ethanolic(50%) fruit extract ofS. xanthocarpum(100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid(I) 7.5 mg/kg, rifampicin(R) 10 mg/kg and pyrazinamide(P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatise(ALP), total bilirubin(TBL), albumin(ALB), total protein(TP), lactate dehydroginase(LDH), and serum cholesterol(CHL). Meanwhile,in vivoantioxidant activities as lipid peroxidation(LPO), reduced glutathione(GSH), superoxide dismutase(SOD) and catalase(CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination.Results:The results demonstrated that treatment withS.xanthocarpumsignificantly(P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore,S. xanthocarpumsignificantly(up toP<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpumattenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration.Conclusions:The results of this study strongly indicate the protective effect of S. xanthocarpumagainst liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.展开更多
AIM: Hepatotoxicity is a significantly increasing health problem worldwide, and the extent of the problem has stimulated interest in the search for hepatotherapeutic agents from plants. This study investigated the hep...AIM: Hepatotoxicity is a significantly increasing health problem worldwide, and the extent of the problem has stimulated interest in the search for hepatotherapeutic agents from plants. This study investigated the hepatoprotective and in vivo antioxidant activities of the hydroethanolic extract of Mucuna pruriens leaves in antitubercular and alcohol-induced hepatotoxicity assays in rats. METHOD: In each of the models used, seven groups were allotted. The different groups received normal saline(10 mL·kg-1, p.o.); hepatotoxicant(isoniazid-rifampicin, INH-RIF, 100 mg·kg-1, i.p. or 20% ethanol 5 g·kg-1, p.o.) and normal saline(10 mL·kg-1, p.o.); hepatotoxicant and extract at doses of 100, 200, and 400 mg·kg-1 p.o.; hepatotoxicant and silymarin 50 mg·kg-1 p.o.; and extract at 400 mg·kg-1 p.o.. On the 21st day of treatment, blood was collected for assessment of serum biochemical parameters and harvested liver samples were assessed for antioxidants. RESULTS: The hepatotoxicants significantly(P < 0.05-0.001) increased the levels of alanine transaminase(ALT), aspartate transaminase(AST), alkaline phosphatase(ALP), bilirubin, and malondialdehyde(MDA); and reduced the levels of catalase(CAT), superoxide dismutase(SOD), glutathione peroxidase(GPx), and reduced glutathione GSH compared to control. M. pruriens significantly reversed(P < 0.05-0.001) the elevation in the level of ALT, AST, ALP, and bilirubin caused by the hepatotoxicants. The extract(200 and 400 mg·kg-1) significantly reversed(P < 0.05) the diminution in the level of in vivo antioxidants and increased the level of MDA produced by INH-RIF. M. pruriens(100-400 mg·kg-1) elicited significant reduction(P < 0.001) in the level of MDA compared to the alcohol group. Silymarin also reversed the deleterious effects of the hepatotoxicants. CONCLUSION: The hydroethanolic extract of Mucuna pruriens leaves possesses hepatoprotective activity with enhancement of in vivo antioxidants as a possible mechanism of action.展开更多
Objective:To estimate to what extent the mixture of ursolic acid and oleanolic acid,in addition to the antitubercular standard regime,affects the hepatotoxicity profile.Methods:Liver injury was induced in male BALB/c ...Objective:To estimate to what extent the mixture of ursolic acid and oleanolic acid,in addition to the antitubercular standard regime,affects the hepatotoxicity profile.Methods:Liver injury was induced in male BALB/c mice by administering,per os and daily for 11 weeks,a combination of anti-Tubercular(anti-TB) agents Rifampicin(10 mg/kg),Isoniazid(10 mg/kg),and Pyrazinamide(30 mg/kg).The ursolic acid and oleanolic acid mixture at doses of 100 or 200 μg/mouse/day was subcutaneously injected throughout the entire study period(11 weeks).Biochemical and hematological analysis was supplemented by liver histological examination.Results:Animals treated with the mixture of triterpenic acids exhibited significantly decreased aspartate transaminase and alanine aminotransferase levels and amelioration of the histopathological alterations produced by the anti-TB drugs.Conclusions:The triterpene mixture is able to prevent the steatosis induced by the anti-TB drugs.展开更多
Tuberculosis(TB)has been a human disease for centuries.Its frequency is increased manyfold in patients with liver cirrhosis.The gold standard of TB management is a 6-mo course of isoniazid,rifampicin,pyrazinamide and ...Tuberculosis(TB)has been a human disease for centuries.Its frequency is increased manyfold in patients with liver cirrhosis.The gold standard of TB management is a 6-mo course of isoniazid,rifampicin,pyrazinamide and ethambutol.Although good results are seen with this treatment in general,the management of patients with underlying cirrhosis is a challenge.The underlying depressed immune response results in alterations in many diagnostic tests.The tests used for latent TB have many flaws in this group of patients.Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis.Frequency of hepatotoxicity is increased in patients with liver cirrhosis,frequently leading to severe liver failure.There are no established guidelines for the treatment of TB in relation to the severity of liver disease.There is no consensus on the frequency of liver function tests required or the cutoff used to define hepatotoxicity.No specific treatment exists for prevention or treatment of hepatotoxicity,making monitoring even more important.A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment.展开更多
基金Part of this manuscript was supported by Grant from the Instituto Mexicano del Seguro Social,projects FIS/IMSS/PROT/G15/1414
文摘Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and Pub Med.
基金financially supported by Department of Science&Technology,Government of India,New Delhi(Grant no.GAP-274625)
文摘Objective:To assess the hepatoprotective effect of Solanum xanthocarpum(S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals.Methods:Ethanolic(50%) fruit extract ofS. xanthocarpum(100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid(I) 7.5 mg/kg, rifampicin(R) 10 mg/kg and pyrazinamide(P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatise(ALP), total bilirubin(TBL), albumin(ALB), total protein(TP), lactate dehydroginase(LDH), and serum cholesterol(CHL). Meanwhile,in vivoantioxidant activities as lipid peroxidation(LPO), reduced glutathione(GSH), superoxide dismutase(SOD) and catalase(CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination.Results:The results demonstrated that treatment withS.xanthocarpumsignificantly(P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore,S. xanthocarpumsignificantly(up toP<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpumattenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration.Conclusions:The results of this study strongly indicate the protective effect of S. xanthocarpumagainst liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.
文摘AIM: Hepatotoxicity is a significantly increasing health problem worldwide, and the extent of the problem has stimulated interest in the search for hepatotherapeutic agents from plants. This study investigated the hepatoprotective and in vivo antioxidant activities of the hydroethanolic extract of Mucuna pruriens leaves in antitubercular and alcohol-induced hepatotoxicity assays in rats. METHOD: In each of the models used, seven groups were allotted. The different groups received normal saline(10 mL·kg-1, p.o.); hepatotoxicant(isoniazid-rifampicin, INH-RIF, 100 mg·kg-1, i.p. or 20% ethanol 5 g·kg-1, p.o.) and normal saline(10 mL·kg-1, p.o.); hepatotoxicant and extract at doses of 100, 200, and 400 mg·kg-1 p.o.; hepatotoxicant and silymarin 50 mg·kg-1 p.o.; and extract at 400 mg·kg-1 p.o.. On the 21st day of treatment, blood was collected for assessment of serum biochemical parameters and harvested liver samples were assessed for antioxidants. RESULTS: The hepatotoxicants significantly(P < 0.05-0.001) increased the levels of alanine transaminase(ALT), aspartate transaminase(AST), alkaline phosphatase(ALP), bilirubin, and malondialdehyde(MDA); and reduced the levels of catalase(CAT), superoxide dismutase(SOD), glutathione peroxidase(GPx), and reduced glutathione GSH compared to control. M. pruriens significantly reversed(P < 0.05-0.001) the elevation in the level of ALT, AST, ALP, and bilirubin caused by the hepatotoxicants. The extract(200 and 400 mg·kg-1) significantly reversed(P < 0.05) the diminution in the level of in vivo antioxidants and increased the level of MDA produced by INH-RIF. M. pruriens(100-400 mg·kg-1) elicited significant reduction(P < 0.001) in the level of MDA compared to the alcohol group. Silymarin also reversed the deleterious effects of the hepatotoxicants. CONCLUSION: The hydroethanolic extract of Mucuna pruriens leaves possesses hepatoprotective activity with enhancement of in vivo antioxidants as a possible mechanism of action.
基金partly supported by Grant from the Instituto Mexicano del Seguro Social (NO.FIS/IMSS/PROT/G12/1126FIS/IMSS/PROT/G14/1341)
文摘Objective:To estimate to what extent the mixture of ursolic acid and oleanolic acid,in addition to the antitubercular standard regime,affects the hepatotoxicity profile.Methods:Liver injury was induced in male BALB/c mice by administering,per os and daily for 11 weeks,a combination of anti-Tubercular(anti-TB) agents Rifampicin(10 mg/kg),Isoniazid(10 mg/kg),and Pyrazinamide(30 mg/kg).The ursolic acid and oleanolic acid mixture at doses of 100 or 200 μg/mouse/day was subcutaneously injected throughout the entire study period(11 weeks).Biochemical and hematological analysis was supplemented by liver histological examination.Results:Animals treated with the mixture of triterpenic acids exhibited significantly decreased aspartate transaminase and alanine aminotransferase levels and amelioration of the histopathological alterations produced by the anti-TB drugs.Conclusions:The triterpene mixture is able to prevent the steatosis induced by the anti-TB drugs.
文摘Tuberculosis(TB)has been a human disease for centuries.Its frequency is increased manyfold in patients with liver cirrhosis.The gold standard of TB management is a 6-mo course of isoniazid,rifampicin,pyrazinamide and ethambutol.Although good results are seen with this treatment in general,the management of patients with underlying cirrhosis is a challenge.The underlying depressed immune response results in alterations in many diagnostic tests.The tests used for latent TB have many flaws in this group of patients.Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis.Frequency of hepatotoxicity is increased in patients with liver cirrhosis,frequently leading to severe liver failure.There are no established guidelines for the treatment of TB in relation to the severity of liver disease.There is no consensus on the frequency of liver function tests required or the cutoff used to define hepatotoxicity.No specific treatment exists for prevention or treatment of hepatotoxicity,making monitoring even more important.A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment.
