Mechanisms of Action of Diallyl Disulfide Against Trichloromethane-Induced Renal Toxicity is Via Inhibitions of Oxidative Stress, NFkB Activation, and Apoptosis in Rats

Abstract

The renal-protective effect of diallyl disulfide (DADS) on tricholoromethane (CHCl₃)-induced renal toxicity was investigated. Twenty five rats, divided into five groups of five animals each were used. CHCl₃ at the dose of 200 mg/kg was orally administered, and concomitantly treated with DADS (50 mg/kg), 5 days/week for a period of 3 weeks. Compared with control, there was no significant increase in kidney malondialdehyde (MDA), but a significant increase in levels of nuclear factor kappa B (NFkB) expressions, TUNEL positive cells (apoptosis), as well as hydrogen peroxide (H₂O₂), nitric oxide (NO) and reduced glutathione (GSH) concentrations. In addition, a significant decrease in expressions of kidney p53 and catalase (CAT) activity, and a non-significant decrease in glutathione peroxidase (GPx) activity were recorded following CHCl₃ administration.  Conversely, following DADS treatment, there was a significant increase in the expressions of p53, and a significant and non-significant decrease in apoptotic positive cells and NFkB expressions respectively. Administration of DADS significantly reduced the levels of H₂O₂ and NO, but did not have effect on the level of GSH, while CAT and GPx activities were significant improved. Protection by DADS against TCM-induced renal-toxicity may therefore be via suppressions of NFkB activation, oxidative stress and apoptosis in rats.

Keywords: Apoptosis, Diallyl disulfide, NFkB, Oxidative stress, p53, Trichloromethane