Temporal Variation in Murine Kidney Toxicity to the Antituberculosis Agent (Isoniazid)

Abstract

Background: Isoniazid is a drug largely used for both the treatment and prophylaxis of Tuberculosis. In this study, we investigated whether INH-induced nephrotoxicity is influenced by dosing-time. Materials and Methods: A potentially toxic INH dose (120 mg/kg) was injected by i.p. route to different groups of animals at three different circadian times: 1, 9 and 17 hours after light onset (HALO). INH administration at 1 and 9 HALO resulted in maximum and minimum nephrotoxicity respectively. Toxicity was assessed by the significant increase in both biochemical parameters of kidney function (Urea: URE, Uric Acid: URI and Creatinine: CERT) and stress oxidative (Malondialdehyde: MDA). These results were correlated with the severe and minor renal histopathological observed at 1 and at 9 HALO respectively. Conclusion: The optimal tolerance or least side effects were detected when INH was injected in the second part of the light-rest span (9 HALO) of mice.