Abstract
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.
Aamna Khokhar, Sadia Shaukat, Aisha Qayyum, Jawaria Iftikhar, Rukhsana Munawar. (2020) Potentiation of Hepatotoxic Effects of Methotrexate by Isoniazid in Mice; an Explorative Study, International Journal of Pathology, Volume-18, Issue-4.
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