Edaravone Mitigates Di(2-ethylhexyl) Phthalate-Induced Nephrotoxicity Through Attenuation of Oxidative Stress and Endoplasmic Reticulum Stress.

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in various plastic items and is hazardous for the environment with significant nephrotoxic potential. Edaravone is a potent anti-oxidant that strongly scavenges the free radicals and protects the cells against oxidative stress. The objective of the present study was to examine the ameliorative potential of edaravone against DEHP-induced nephrotoxicity via targeting oxidative stress and ER stress-related proteins. Twenty-four male albino Wistar rats were randomly divided into four groups. The control group received corn oil orally for 28 days. The DEHP group received DEHP (500 mg/kg, p.o.) for 28 days. Additionally, two treatment groups received 500 mg/kg DEHP for 28 days and edaravone (5 and 10 mg/kg) for the last 14 days (Days 15 to 28). On the 29th day, animals were euthanized, and blood and kidney samples were collected. The renal function test, oxido-nitrosative stress parameters, and histopathology analysis were performed along with the western blotting test. Findings revealed that DEHP significantly increased levels of BUN, creatinine, and urea along with a substantial reduction in GSH levels and an increase in MDA and nitrite levels. The DEHP group also showed upregulated protein levels of GRP78, CHOP, and caspase-12. These alterations were accompanied by histological damage. Edaravone treatment alleviated DEHP-induced renal injury by modulation of oxidative stress and ER stress-related markers. These findings give us a mechanistic insight on how edaravone can regulate ER stress-related proteins in DEHP-induced nephrotoxicity and provide its ameliorative effect.