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Effect of cimetidine on hepatotoxicity induced by isoniazid-rifampicin combination in rabbits
Bhupinder Singh Kalra1, Sarita Aggarwal, Nita Khurana
1Department of Pharmacology, Maulana Azad Medical College, New Delhi 110 002, India. drbskalra@gmail.com
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.
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