Abstract: Objective To determine the effect of bicyclol against oxaliplatin/5 -fluorouracil -induced hepatotoxicity and the influence on the antitumor capacity of oxaliplatin/5 -fluorouracil in tumour -bearing mice. Methods C57/ BL mice implanted with Lewis lung tumors for6 days were treated with oxaliplatin(6mg·kg^-1×1) and 5-fluorouracil (25mg·kg^-1×5) to establish the liver damage model. Bicyclol(150,300mg·kg^-1) was pretreated 2hr before the injection of oxaliplatin/5-fluorouracil. All animals were killed on the eighth day after oxaliplatin/5-fluorouracil treatment and tumor weight of each animal was measured. The activities of ALT and AST were meseared by automatic chemistry analyzer(TBA-40FR). Liver histopathological changes were examined by H.E. and light microscopy. Results The combination therapy of oxaliplatin and 5-fluorouracil significantly inhibited the growth of Lewis lung tumor and the inhibiton rate is 72.7% . At the same time, the obvious toxic reaction emerged expressed as 26.7% mice were death, the pathology of liver tissue was damaged and the serum aminotransferases were elevated. Bicyclol showeda significant protection as evidenced by the improvement of histotpathological injury and the decrease of elevated serum amino-transferases induced by oxaliplatin/5-fluorouracil. The administration of bicyclol could also reduce the mortality and increase slightly the anti-tumor activity of oxaliplatin/5-fluorouracil. Conclusion Bicyclol showed potent protective activity against oxaliplatin/5-fluorouracil-induced liver damage and decreased the death by the high-dose chemotherapy without affecting the associated inhibition of tumor growth. This maybe provide a new approach for preventing the hepatotoxicity induced by oxaliplatin/5-fluorouracil in the clinic.

Key words: bicyclol, oxaliplatin, 5-fluorouracil, liver damage