Objective: To evaluate the effect of isoniazid on methotrexate induced hepatotoxicity.
Study Design: Laboratory-based experimental study
Place and Duration of Study: Department of Pharmacology Army Medical College, from November 2015 to November
2016.
Material and Methods: Thirty mice were randomly divided into five groups (n=6). Group Ⅰ was given 0.2 ml normal
saline by intraperitoneal injection. Group Ⅱ received 0.2 ml of distilled water by oral gavage for 5 days a week for 4 weeks.
Group Ⅲ received single intraperitoneal injection of methotrexate 20 mg/kg. Group Ⅳ received Isoniazid 25 mg/kg oral for
5 days a week for 4 weeks. Group Ⅴ received Isoniazid 25 mg/kg oral for 5 days a week for 4 weeks and methotrexate 20
mg/kg i.p after two weeks. Blood samples for measuring serum ALT, AST and ALP along with liver samples for hepatic
histological H&E examination were taken after 24 hours of last dose.
Results: Serum ALT, AST, ALP levels were significantly raised in group V (MTX + INH) higher than all other groups
exhibiting significant potentiation of MTX induced hepatotoxicity by INH. Histologically group III (MTX) and group IV
(INH) showed mild to moderate inflammatory changes whereas group V (MTX + INH) were graded as severe
hepatotoxicity with Central vein ischemic changes
Conclusion: It was concluded from results that Isoniazid Potentiates Hepatotoxic effects of Methotrexate in mice as
evidenced by histological changes and elevated hepatic enzymes.