Effect of different doses of carotenoids in isoniazid-rifampicin induced hepatotoxicity in rats.
OBJECTIVE
Isoniazid (INH) and Rifampicin (RIF) are hepatotoxic drugs. Oxidative stress has been reported as one of the mechanisms of INH+RIF induced hepatotoxicity.


METHODS
Intragastric administration of INH and RIF (50 mg/kg body weight/day each) for 28 days in Wistar rats is hepatotoxic, indicated by raised transaminases and histology. Carotenoids have antioxidant properties. Therefore, different doses of carotenoids (2.5, 5, 10 and 20 mg/kg body weight/day) were administered to study the hepatoprotective effect against INH+RIF.


RESULTS
The higher doses of carotenoids i.e.10 and 20 mg/kg body weight/day showed partial hepatoprotection indicated by return to normal of liver transaminase level and of liver histology in 33.3% of rats. There was no further protective effect seen by increasing the dose of carotenoids from 10 to 20 mg/kg body weight/day. Lower doses of carotenoids, i.e., 2.5 and 5 mg/kg body weight/day were not effective.


CONCLUSIONS
Thus, a minimum dose with maximum hepatoprotection (10 mg/kg b.wt/ day) was selected as the optimum dose in the present study. The hepatoprotective nature of carotenoids in INH+RIF treated rats may be attributed to their antioxidative property.
Pal
Ravinder
R
Department of Gastroenterology & Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Rana
Satyavati
S
Vaiphei
Kim
K
Singh
Kartar
K
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D000995:Antitubercular Agents / Q000009:adverse effects*; D002338:Carotenoids / Q000008:administration & dosage*; D056486:Chemical and Drug Induced Liver Injury; D004305:Dose-Response Relationship, Drug; D007538:Isoniazid / Q000009:adverse effects*; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000009:adverse effects*
D000975:Antioxidants; D000995:Antitubercular Agents; D002338:Carotenoids; D007538:Isoniazid; D012293:Rifampin