Isoniazid-induced hepatic necrosis and steatosis in rabbits: absence of effect of gender.
Isoniazid, a highly effective drug for the chemoprophylaxis and treatment of tuberculosis, is associated with severe hepatotoxicity in 1-2% of individuals. In a rabbit model of isoniazid-induced hepatotoxicity, we have measured hepatic necrosis (quantitated by elevation of plasma argininosuccinic acid lyase (ASAL) activity), hepatic steatosis (quantitated by elevation of hepatic triglyceride content), and elevation in plasma triglyceride concentration in 15 rabbits. Eight of 15 rabbits were male, and 14 of 15 were rapid acetylators of sulfamethazine. Administration of isoniazid to rabbits resulted in a 27-fold increase in plasma ASAL activities, a 7.5-fold increase in hepatic triglyceride content, and a 13-fold increase in plasma triglyceride levels. This study demonstrated no effect of gender on these three pathological changes that occur in this model of isoniazid-induced hepatotoxicity in rabbits.
Sarich
T C
TC
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Adams
S P
SP
Zhou
T
T
Wright
J M
JM
D000818:Animals; D000995:Antitubercular Agents / Q000633:toxicity*; D001123:Argininosuccinate Lyase / Q000097:blood; D005234:Fatty Liver / Q000097:blood / Q000139:chemically induced / Q000473:pathology*; D005260:Female; D015228:Hypertriglyceridemia / Q000097:blood / Q000139:chemically induced; D007538:Isoniazid / Q000633:toxicity*; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009336:Necrosis; D010641:Phenotype; D011817:Rabbits; D012737:Sex Factors; D013418:Sulfamethazine / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D000995:Antitubercular Agents; D014280:Triglycerides; D013418:Sulfamethazine; D001123:Argininosuccinate Lyase; D007538:Isoniazid