Abstract: ObjectiveTo assess the hepatoprotective effect of a water solubility derivative of biphenyl by three acute liver failure models. MethodsTwo mice models of acute liver failure were established by injection with carbon tetrachlo-ride(CCl4) or concanavalin A(Con A) respectively. Mice were intraperitoneally injected with two doses of WLP-S-14(100 200 mg·kg-1) before administration of CCl4 and Con A. Serum alanine aminotransferase(ALT) and glutamate oxaloacetate transaminase(AST) were detected by automatic chemistry analyzer(TBA-40FR). At the same time, oxaliplatin and 5-fluorouracil were injected to induce liver failure in Lewis-bearing mice. WLP-S-14(100,200mg·kg-1) was pretreated 2hr before the injection of oxaliplatin/5-fluorouracil. The activities of ALT and AST in serum were measured by automatic chemistry analyzer and liver histopathological changes were examined by H.E. and light microscopy. ResultsIn CCl4-induced liver damage mice, WLP-S-14 100mg·kg-1 significantly reduced the elevated serum AST and ALT levels induced by CCl4. WLP-S-14 200mg·kg-1 also markedly decreased sersum ALT, but there was no significantly statistical significance on the decrease of AST when compared with the model group. In Con A-induced immunologic liver injury mice, pretreation of WLP-S-14(100 200mg·kg-1) both markedly decreased the elevated ALT and AST induced by Con A. WLP-S-14(100, 200mg·kg-1) also showed a significant protection in oxaliplatin/5-fluorouracil-induced liver damage mice, as evidenced by the improvement of histopathological injury and the decrease of elevated serum aminotransferases. There was no decline to tumor inhibition rate produced by oxaliplatin/5-fluorouracilwhenco-administration WLP-S-14 100mg·kg-1. ConclusionWLP-S-14 showed potent protective activities against CCl4, Con A or oxaliplatin/5-fluorouracil-induced liver damage. It is worth exploring for future study.

Key words: derivative of biphenyl, bicyclol, water solubility, liver injury