PROTECTIVE EFFECT OF ISONIAZID ON THIONAMIDE INDUCED IN MICE
Methimazole (MMI) is a widely used antithyroid drug for hyperthyroidism.
However its clinical use is associated with many deleterious effects including hepatotoxicity.
MMI induced liver injury is dependent upon bio-activation to toxic intermediates revealing the
important role of drug metabolizing enzymes in generation of this adverse reaction. Study
design: Randomized controlled laboratory trial. Period: 04 months from March 2015 to June
2015. Settings: Department of Pharmacology and Therapeutics, Army Medical College,
Rawalpindi. Aim of the study: The effect of isoniazid (INH) on MMI induced hepatotoxicity was
evaluated in mice. Materials and Method: Thirty male BALB/c mice were randomly divided
into five groups. Group I served as control group (C-I). Group II (C-II) served as control for
INH treated group and received plain drinking water for ten consecutive days. Hepatotoxicity
was induced by single intraperitoneal injection of MMI at a dose of 1000mg/kg in Group III
(MMI).Group IV (INH) received isoniazid (0.1%w/v) in drinking water for ten consecutive days.
A separate group V (INH +MMI) of isoniazid pretreated mice was given MMI at eleventh day for
determination of combined effect of both drugs. The extent of hepatic damage was determined
by estimation of serum ALT and ALP along with histopathological analysis of liver samples.
Results: MMI resulted in markedly elevated ALT and ALP with hepatic inflammation. INH
administration produced no significant change in both serum biomarkers and histopathology
appearance. Pretreatment of INH with MMI produced insignificant escalation of liver enzymes
and microscopic parameters. However, biochemical and histological comparison of this group
with MMI group revealed statistically consequential differences. Conclusion: INH has beneficial
role in preventing MMI induced hepatic injury.