Hepatoprotective Effects Of Silibin On α-amanitin-induced Liver Injuey In Mice

Objective: The aim of the present study was to set up acute mice liver injury model caused by α-amanitin and evulate the hepatoprotective effect.Method: The LD50 and LD90 of α-amanitin in mice was calculated by the improved karber method. By measuring the content of AST,ALT, MDA,GSH and SOD, the LD50 of α-amanitin was used to establish time-activity-curve of α-amanitin on biochemical in mice and assess therapeutic effect of silibin.The LD50 α-amanitin-induced liver injuey model was ued to compare treatment of α-amanitin poisoning with diammonium glycyrrhizinate, tiopronin, reduced glutathione sodium and polyene phosphatidyl choline.The protective and curative treatment effect of silibin on the mice poisoned by LD90 α-amanitin was investigated from mortality. Prevention group of silibinin doses were 120, 240, 480mg/kg 60 min before the adminsteration of LD90 α-amanitin, with intravenous injection. The curative treatment group of silibinin is divided into different time groups, which respectively were 10, 20, 40, 60 min after intraperitoneal injection of LD90 α-amanitin.The curative treatment effect of silibin on the mice poisoned by LD90 α-amanitin was investigated from mortality and the pathological of liver and kidney. Silibin was administrated 10 min after the injection of LD90 α-amanitin. The effects of silibin were inspected by measuring the content of AST,ALT, MDA,GSH,SOD and observing the pathological of liver and kidney. Silibin was also administrated 10 min after the injection of LD50 α-amanitin.Result: Acute liver injury in mice induced by LD50 and LD90 α-amanitin toxic peptides respectively are 0.36mg/kg and 0.50 mg/kg.After intravenous LD50 α-amanitin, the contnent of AST and ALT sharply raised,began to decline after 36 h and achieved normal levels at 72 h.CRE and BUN had a significant rise in 60 h.MDA and SOD were significantly elevated in 12 ~ 72 h, GSH significant declined in this period.Compared with model group,the content of AST,ALT, MDA,GSH and SOD of glycyrrhizinate, tiopronin, reduced glutathione sodium and polyene phosphatidyl choline had no significant differences. Four drugs for cute liver injury in mice induced by LD50 α-amanitin were no therapeutic effect.All mice were protected by silibin which was adminstrated 60 min before intraperitoneal of LD90 α-amanitin. Curative treatment with silibin is very effective when administered 10 min after the toxin.The anti-α-amanitin effect diminishes when silibin was administered 20 min after poisoning and disappeared when silibin was administered 40 min after poisoning.All mice were protected by silibin which was adminstrated 10 min after intraperitoneal of LD90 α-amanitin. Compared with the blank group, model group AST, ALT, MDA and GSH levels increased, SOD activity decreased significantly, compared with the model group.Silibin significantly decreased serum ALT, AST,MDAand GSH levels, increased SOD activities, when administered 10 min after administration LD50 α-amanitin. From the observation of pathological picture,it was clearly that the model group’s structure of hepatic lobule were not clear, hepatic cell cords disordered, liver cell edema, part of a vacuolar changed, spotty necrosis of liver tissue, silibinin group improved significantly.Conclusion: Silibin had good effect to treat the injury of α-amanitin induced acute liver.