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.


CONCLUSIONS
Cimetidine in high dose can prevent hepatotoxicity induced by isoniazid-rifampicin combination.
Kalra
Bhupinder Singh
BS
Department of Pharmacology, Maulana Azad Medical College, New Delhi 110 002, India. drbskalra@gmail.com
Aggarwal
Sarita
S
Khurana
Nita
N
Gupta
Usha
U
D000818:Animals; D000995:Antitubercular Agents / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D002927:Cimetidine / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007538:Isoniazid / Q000633:toxicity*; D008111:Liver Function Tests; D011817:Rabbits; D012293:Rifampin / Q000633:toxicity*; D018709:Statistics, Nonparametric
D000995:Antitubercular Agents; D006635:Histamine H2 Antagonists; D002927:Cimetidine; D007538:Isoniazid; D012293:Rifampin