Effect of different oral doses of isoniazid-rifampicin in rats.
Hepatotoxicity is one of the most serious adverse effects of antituberculosis drugs. The aim of this study was to produce a rat model of isoniazid-rifampicin (INH-RIF) induced hepatotoxicity.


METHODS
Wistar rats (100-150 g) were treated with different doses of INH i.e. 25, 50 and 75 mg/kg/day with a fixed dose of RIF i.e. 50 mg/kg/day intragastrically for a period of 28 days. Serum glutamate oxaloacetate aminotransferase (SGOT), glutamate pyruvate aminotransferase (SGPT), bilirubin (Bil) and alkaline phosphatase (ALP) were estimated at 0,14, 21 and 28 days in rats. Histological analysis was carried out to assess the liver.


RESULTS
Treatment of rats with INH-RIF (50 mg/kg/day each) induced hepatotoxicity as judged by elevated serum SGPT, SGOT, Bil and ALP as compared with their base line. Histological evaluation of INH-RIF induced hepatotoxicity also showed liver damage.


CONCLUSIONS
The present study suggests that 50 mg/kg/day each of INH-RIF was selected as hepatotoxic dose (i.e. minimum dose with maximum hepatotoxicity) in wistar rats.
Rana
Satya V
SV
Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Pal
Ravinder
R
Vaiphie
Kim
K
Singh
Kartar
K
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D007538:Isoniazid / Q000008:administration & dosage* / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000008:administration & dosage* / Q000494:pharmacology*
D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin; D007538:Isoniazid; D012293:Rifampin