Acrylamide-induced nephrotoxicity mediated through endoplasmic reticulum stress pathway in rat kidney: protective...

The current study aims to explore the role of endoplasmic reticulum stress (ER stress) in acrylamide (ACR)-induced nephrotoxicity. In addition, the role of ER stress is pharmacologically validated by a chemical chaperone, 4-phenylbutyric acid (4-PBA). In the present study, 24 male Albino Wistar rats (n = 6) were randomly divided into four groups. The control group received normal saline orally (p.o.) for 4 weeks. The acrylamide toxic group received ACR (10 mg/kg, p.o. in normal saline) for 4 weeks. The 4-PBA treatment groups received ACR for 28 days and 4-PBA (500 mg/kg and 1000 mg/kg, p.o. in saline) for the last 14 days. On the 29^th day, rats were euthanized, and blood as well as kidney samples were collected. Renal function parameters along with oxido-nitrosative stress biomarkers in kidney were analyzed. Western blotting was used to quantify the protein expression of key ER stress indicators, and finally, histopathological examination was conducted. Findings from the study indicated that ACR markedly increased the levels of kidney function markers, renal oxido-nitrosative stress, upregulated protein expression of ER stress-related proteins and disrupted normal morphology as compared to the control group. However, 4-PBA treatment reduced oxido-nitrosative stress, improved renal functioning, downregulated ER stress-related proteins and recovered the distorted morphology of the rat's kidney. These findings suggest the significant role of ER stress in the progression of ACR-induced nephrotoxicity as well as the ameliorative effect of 4-PBA against ACR-induced nephrotoxicity. Moreover, our findings provide the first evidence that activation of the ER stress pathway plays a critical role in acrylamide-induced nephrotoxicity.