Diallyl trisulfide, a garlic polysulfide protects against As-induced renal oxidative nephrotoxicity, apoptosis and inflammation in rats by activating the Nrf2/ARE signaling pathway

- Arsenic nephrotoxicity is still one of the major ailments in As contaminated regions.
- Arsenic induces the oxidative stress, inflammation and apoptosis in the renal tissue.
- DATS supplementation attenuates oxidative stress mediated renal injury by As.
- DATS supplementation suppresses inflammation and apoptosis via its antioxidant efficacy.
- DATS have potential to induce antioxidant system via Nrf2/Keap1 activation.

BackgroundArsenic (As) contamination is an extremely dangerous global environmental problem as it can enter into the food chain and become bio-accumulated, endangering human health. Chronic As intoxication leads to undesirable toxic effects in various organ systems of the body, especially the kidney. Diallyl trisulfide (DATS) is an organosulfur compound which has been widely known for its uses as antibacterial, antitumorogenic, antioxidant agent and has been also reported to have anti-apoptotic and anti-inflammatory properties.PurposeIn the present work, we intend to investigate the protective role of DATS, a garlic organosulfur compound in preventing the As-induced oxidative stress mediated renal injury in rats.Study designThe activity of DATS to antagonize As-induced renal oxidative toxicity was analyzed using rats as an in vivo model.MethodsWe investigated the nephroprotective effect of DATS on As treated rats by performing various serological, biochemical, molecular and histological studies. The activation of Nrf2 was investigated using western blot.ResultsThe data showed that As exposure significantly increased the serum and urine nephritic, oxidative stress, apoptosis and inflammatory markers in the renal tissue of rats. As intoxication also decreased the antioxidant status of the renal tissue along with the disturbances in the membrane bound ATPases. As nephrotoxicity was further confirmed with the altered morphological and ultrastructural changes in the renal tissue. Conversely, the DATS pre-administration effectively recuperate the altered renal variables by As, which has been further supported by the histological and ultrastructural observations. This counteraction was achieved partially via the activation of Nrf2-ARE pathway through the activation of Akt.ConclusionThese findings explicate the prospective use of DATS as a promising organosulfur compound against As-induced renal oxidative dysfunction in rats.

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