Protective Effect of Curcumin Against Gentamicin-induced Nephrotoxicity Mediated by p38 MAPK, Nuclear FactorKappa B, Nuclear Factor Erythroid 2-Related Factor 2

Introduction. The antioxidant activity of curcumin (CMN) has been evaluated in several studies. We aimed to examine the protective effect of curcumin on gentamicin-induced nephrotoxicity in rats, both at histological and immunohistochemical levels. Methods. Forty male Wistar albino rats were assigned into four groups of 10 as follows: group 1: control, group 2: curcumin for 15 days, group 3: gentamicin for the last 10 days, and group 4: curcumin for 15 days and gentamicin for the last 10 days. Curcumin (100 mg/kg/d) was gavaged, and gentamicin (80 mg/kg/d) was injected intraperitoneally. Kidney tissues and blood were collected for histological, immunohistochemical and biochemical studies. Body weight and kidney weight/body weight changes were recorded. Results. Gentamicin nephrotoxicity was characterized by a significant rise in serum urea and creatinine levels and a significant reduction in body weight and an increase in kidney weight/body weight. The gentamicin group showed degenerative changes in tubules and glomeruli together with, increased phosphorylated (p)-p38 mitogen-activated protein kinase (p38 MAPK) positive cells in immunohistochemical evaluation, increased immunoreactivity of nuclear factor-kappa B (NFkB), and decreased immunoreactivity of nuclear factor erythroid 2-related factor 2 (Nrf2). Curcumin diminished body weight loss caused by gentamicin administration but, did not change the kidney weight/body weight. Moreover, curcumin ameliorated the histological alterations and reduced the biochemical parameters. Additionaly, curcumin significantly decreased p-p38 MAPK positive cells and NFkB immunoreactivity, while significantly increasing Nrf2 immunoreactivity in the kidney tissue. Conclusion. We conclude that curcumin may attenuate gentamicininduced nephrotoxicity by supprresing the p38 MAPK and NFkB, and activating the Nrf2 signaling pathways.