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

Abstract

ABSTRACT 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.