Effect of cimetidine on hepatotoxicity induced by isoniazid-rifampicin combination in rabbits.

OBJECTIVE: To evaluate the hepatoprotective potential of cimetidine in hepatotoxicity induced by isoniazid-rifampicin combination in albino rabbits. METHODS: Six groups of six rabbits each were studied. Three groups received saline (control), isoniazid (50 mg/Kg/d) alone or isoniazid with rifampicin (100 mg/Kg/d) daily orally for 7 days. Other groups received intraperitoneal cimetidine (50 mg/Kg/d) alone or cimetidine (50 or 120 mg/Kg/d) along with isoniazid-rifampicin combination. Serum levels of liver enzymes were measured at baseline and on day 8 and liver histology was studied on day 8. RESULTS: Rabbits receiving isoniazid alone for 7 days showed no increase in serum ALT and AST levels, whereas those receiving isoniazid-rifampicin combination had a 3-4-fold increase in these levels (p=0.02). Animals receiving cimetidine pre-treatment did not show a significant increase in ALT and AST levels. Histological changes in the liver were more common with isoniazid-rifampicin combination than with isoniazid only. These changes were reduced in animals receiving low-dose cimetidine and prevented in those receiving high-dose cimetidine. CONCLUSION: Cimetidine in high dose can prevent hepatotoxicity induced by isoniazid-rifampicin combination.

Brain tumor and role of beta-carotene, a-tocopherol, superoxide dismutase and glutathione peroxidase.

The erythrocyte levels of the antioxidant enzymes SOD and GPx, and serum levels of antioxidants vitamins beta-carotene and beta-tocopherol were estimated in various types of brain tumors, and were compared with the levels in controls. Statistically significant (P<.001) diminished levels of beta-carotene, beta-tocopherol, SOD and GPx, were observed in all the brain tumor patients as compared to controls. Malignant tumor also showed a relative decrease in antioxidant levels as compared to benign tumors. Comparison of histopathological sections of brain tumors also suggested a inverse relationship between antioxidant level and grades of malignancy. Marked decrease in antioxidant levels may have a role in genesis of considerable oxidative stress in brain tumors. Furthermore, the degree of decline in antioxidant levels may indicate severity of malignancy in brain tumors.