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

Iran J Kidney Dis. 2022 Mar;16(2):96-107.

Abstract

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. DOI: 10.52547/ijkd.6647.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Curcumin* / pharmacology
  • Drug-Related Side Effects and Adverse Reactions*
  • Gentamicins / toxicity
  • Kidney / pathology
  • Male
  • NF-E2-Related Factor 2 / metabolism
  • NF-E2-Related Factor 2 / pharmacology
  • NF-kappa B / metabolism
  • Rats
  • Rats, Wistar
  • p38 Mitogen-Activated Protein Kinases / metabolism
  • p38 Mitogen-Activated Protein Kinases / pharmacology

Substances

  • Gentamicins
  • NF-E2-Related Factor 2
  • NF-kappa B
  • p38 Mitogen-Activated Protein Kinases
  • Curcumin