title: Lack of liver injury in Wistar rats treated with the combination of isoniazid and rifampicin.
abstract: Isoniazid (INH) can cause serious idiosyncratic liver injury. An animal model would greatly facilitate mechanistic studies, but it is essential that the mechanism in the model be similar to the liver injury that can occur in humans. We attempted to replicate a previous study in which Wistar rats treated with INH and rifampicin (RMP) developed liver injury, which was promising because of its delayed onset similar to the liver injury that can occur in humans. Wistar rats were treated with either a high dose of INH (150 mg/kg/day) or a combination of INH and RMP (75 mg/kg/day and 50 mg/kg/day, respectively) for up to 4 weeks. However, we did not observe any liver injury or evidence of an inflammatory infiltrate as had been reported; rather, we observed an increase in CTLA4-positive cells in the cervical lymph nodes as well as a decrease in serum CXCL1 and MCP-1. In short, we were unable to reproduce a previously reported model of delayed onset INH-induced liver injury in Wistar rats.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada, imir.metushi@mail.utoronto.ca.
authors.forename: Imir G
authors.initials: IG
authors.lastname: Metushi
authors.forename: Jack
authors.initials: J
authors.lastname: Uetrecht
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000995:Antitubercular Agents / Q000633:toxicity*; D060908:CTLA-4 Antigen / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004359:Drug Therapy, Combination; D005969:Glutamate Dehydrogenase / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007538:Isoniazid / Q000633:toxicity*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D009333:Neck; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000633:toxicity*; D013385:Succinate Dehydrogenase / Q000097:blood
chemical_list: D000995:Antitubercular Agents; D060908:CTLA-4 Antigen; C556708:Ctla4 protein, rat; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D013385:Succinate Dehydrogenase; D005969:Glutamate Dehydrogenase; D000410:Alanine Transaminase; D007538:Isoniazid; D012293:Rifampin