A model of isoniazid-induced hepatotoxicity in rabbits.
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| Abstract |
Isoniazid (INH) continues to be an effective drug used for chemoprophylaxis and treatment of tuberculosis. Unfortunately, INH is associated with significant hepatotoxicity in up to 2% of individuals exposed, and if this adverse event is not recognized early it can be fatal. Research on INH-induced hepatotoxicity has been hampered by the lack of a suitable animal model that closely resembles the toxicity in humans. The mechanism of INH-induced hepatotoxicity is still unknown. The present study describes the development of a reliable model of INH-induced hepatotoxicity in rabbits. The protocol involves repeated injections of INH over a 2-day period, resulting in significant hepatic necrosis as indicated by elevations of plasma argininosuccinic acid lyase activity. Pretreatment with phenobarbital increased the occurrence of INH-induced hepatic necrosis from approximately 60% (9 out of 15 rabbits) with INH alone to more than 90% (13 out of 14 rabbits). Morphological indices were used to demonstrate the presence of INH-induced hepatotoxicity, and biochemical indices were used to demonstrate both the presence and severity of INH-induced hepatotoxicity in this model. This model may prove useful for further investigations into the mechanism of INH-induced hepatotoxicity.
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| Authors | T C Sarich, T Zhou, S P Adams, A I Bain, R A Wall, J M Wright |
| Journal | Journal of pharmacological and toxicological methods (J Pharmacol Toxicol Methods) Vol. 34 Issue 2 Pg. 109-16 (Oct 1995) ISSN: 1056-8719 [Print] United States |
| PMID | 8563032 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.) |
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