Edaravone attenuates acrylamide-induced nephrotoxicity by modulating the endoplasmic reticulum stress pathway in rats.

Acrylamide (ACR) is an environmental toxicant reported to have nephrotoxic effects. Edaravone is a free radical scavenger proven to have antioxidant properties. However, the role of edaravone in regulating endoplasmic reticulum stress (ER stress) in ACR-induced nephrotoxicity remains unclear. Thus, the present study aims to explore the role of ER stress and edaravone in an ACR-induced nephrotoxicity rat model. In this study, 24 male albino Wistar rats were randomly divided into four groups. The control group received normal saline orally for 28 days. The acrylamide group received acrylamide (10 mg/kg) for 28 days. Additionally, two treatment groups received 10 mg/kg ACR for 28 days; afterwards, edaravone at 5 mg/kg and 10 mg/kg was administered for the last 14 days (15-28 days). On the 29th day, all animals were sacrificed, and blood and kidney samples were collected. Renal function test, oxido-nitrosative stress parameters, and histopathological analysis, along with the western blotting analysis, were performed. Results suggest that ACR exposure significantly elevated the levels of BUN, creatinine, and urea. In addition, levels of MDA and nitrite were significantly increased with a significant drop in GSH levels. Further, upregulated protein expressions of GRP78, CHOP, and Caspase-12 were observed in ACR group, indicating activation of ER stress. Histopathological changes in the kidney were also seen along with these alterations. Interestingly, edaravone treatment mitigated all of these detrimental effects. These findings suggest novel mechanistic insights into the therapeutic potential of edaravone against ACR-induced nephrotoxicity by regulating oxidative stress and ER-stress mediated apoptosis.