ISONIAZID-INDUCED HEPATIC-NECROSIS AND STEATOSIS IN RABBITS - ABSENCEOF EFFECT OF GENDER

Isoniazid, a highly effective drug for the chemoprophylaxis and treatm ent 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 (quan titated by elevation of hepatic triglyceride content), and elevation i n plasma triglyceride concentration in 15 rabbits. Eight of 15 rabbits were male, and 14 of 15 were rapid acetylators of sulfamethazine. Adm inistration of isoniazid to rabbits resulted in a 27-fold increase in plasma ASAL activities, a 7.5-fold increase in hepatic triglyceride co ntent, and a 13-fold increase in plasma triglyceride levels. This stud y demonstrated no effect of gender on these three pathological changes that occur in this model of isoniazid-induced hepatotoxicity in rabbi ts.