P-Coumaric Acid Mitigates Doxorubicin-Induced Nephrotoxicity Through Suppression of Oxidative Stress, Inflammation and Apoptosis

Background and Aims. P-Coumaric acid (PCA) is one the compound that has free radical scavenging effects. This study investigates the protective effect of PCA on tissue damage in DOX-induced nephrotoxicity. Methods. Thirty two Wistar rats were divided into control, PCA, DOX (15 mg/kg, i.p.) and DOX plus PCA (100 mg/kg, orally) groups. DOX-induced nephrotoxicity was indicated by marked increase in blood urea nitrogen (BUN) and serum creatinine (Cr) compared to controls. DOX group also showed elevations in lipid peroxidation and reductions in enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). Expression of renal inflammatory cytokines including tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) and apoptosis were also elevated in the DOX group. Results. PCA significantly reversed, nephrotoxicity induced by DOX via lowering BUN, serum Cr and improving histopathological scores as compared to the DOX group. PCA also decreased lipid peroxidation, increased activities of GPx, SOD and CAT, to levels relatively comparable to control. Significant reductions in expression of TNF-alpha, IL-1 beta and apoptosis were also observed following Co-administration of PCA relative to the DOX group. Conclusions. Results describe a protective effect of PCA against DOX-induced nephrotoxicity. This effect is likely facilitated through inhibition of oxidative stress, inflammation and apoptosis. (C) 2019 IMSS. Published by Elsevier Inc.