Melatonin attenuates arsenic induced nephropathy via the regulation of oxidative stress and inflammatory signaling cascades in mice

Arsenic is a potent inducer of several acute and chronic nephrotoxic disorders. It promotes deleterious phenomenon like oxidative stress, inflammation, cell death and altered glucose uptake leading to distorted kidney homeostasis that end up in chronic kidney disease. This study investigated the possible protective role of melatonin; a natural antioxidant produced by the pineal gland, against arsenic induced nephrotoxicity. Melatonin successfully ameliorated arsenic induced renal toxicity both in in vitro and in vivo models. Elevated BUN, creatinine, urine glucose and protein levels and altered renal histopathological conditions were observed in arsenic intoxicated mice. Significant oxidative stress induced damage of biomolecules along with down-regulation in antioxidant enzymes and thiols were also detected in the kidney tissues of arsenic-intoxicated mice. These alterations along with mitochondrial dysfunction ultimately triggered TNF alpha mediated inflammatory and cell death cascades. Interestingly arsenic also led to disruption of glucose uptake in the kidney. These findings suggest that melatonin protects the kidney against toxic effect of arsenic, presumably through its antioxidant, anti-inflammatory and antidiabetic properties by inhibiting inflammatory outburst, apoptosis, necroptosis and stimulating glucose uptake. As melatonin is a natural antioxidant molecule, detailed pharmacokinetic and pharmacodynamic studies are expected to establish it as an effective nephro-protective agent in future.