Mitochondria-mediated mitigatory role of curcumin in cisplatin-induced nephrotoxicity

Cell Biochem Funct. 2013 Dec;31(8):678-84. doi: 10.1002/cbf.2955. Epub 2013 Feb 13.

Abstract

Cisplatin (CP) is one of the most potent chemotherapeutic anti-tumour drugs, and it has been implicated in renal toxicity. Oxidative stress has been proven to be involved in CP-induced toxicity including nephrotoxicity. However, there is paucity of literature involving role of mitochondria in mediating CP-induced renal toxicity, and its underlying mechanism remains unclear. Therefore, the present study was undertaken to examine the antioxidant potential of curcumin (CMN; a natural polyphenolic compound) against the mitochondrial toxicity of CP in kidneys of male rats. Acute toxicity was induced by a single intra-peritoneal injection of CP (6 mg kg(-1) ). We studied the ameliorative effect of CMN pre-treatment (200 mg kg(-1) ) on the toxicity of CP in rat kidney mitochondria. CP caused a significant elevation in the mitochondrial lipid peroxidation (LPO) levels and protein carbonyl (PC) content. Pre-treatment of rat with CMN significantly replenished the mitochondrial LPO levels and PC content. It also restored the CP-induced modulatory effects on altered enzymatic and non-enzymatic antioxidants in kidney mitochondria. We hypothesize that the reno-protective effects of CMN may be related to its predisposition to scavenge free radicals, and upregulate antioxidant machinery in kidney mitochondria.

Keywords: biomarkers; cisplatin; curcumin; mitochondria; nephrotoxicity; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Biomarkers / analysis
  • Cisplatin / administration & dosage
  • Curcumin / administration & dosage
  • Curcumin / metabolism
  • Curcumin / pharmacology*
  • Lipid Peroxidation / drug effects
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Oxidative Stress / drug effects
  • Protein Carbonylation / drug effects
  • Rats
  • Rats, Wistar

Substances

  • Antioxidants
  • Biomarkers
  • Curcumin
  • Cisplatin