Carvedilol protects against the renal mitochondrial toxicity induced by cisplatin in rats

Mitochondrion. 2010 Jan;10(1):46-53. doi: 10.1016/j.mito.2009.09.001. Epub 2009 Sep 17.

Abstract

The clinical use of cisplatin is highly limited by its nephrotoxicity, which has been associated with mitochondrial dysfunction. We investigated the protective effect of carvedilol, an antihypertensive with strong antioxidant properties, against the nephrotoxicity induced by cisplatin in rats. Carvedilol was able to counteract the renal damage by preventing the mitochondrial dysfunction induced by cisplatin. The mitochondrial eletrochemical potential, calcium uptake, respiration and the phosphorylative capacity were preserved by the co-administration of carvedilol. The mechanism of protection probably does not involve alterations in the cellular and sub-cellular distribution of cisplatin. The study suggests that carvedilol is a potential drug for the adjuvant nephroprotective therapy during cisplatin chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacology
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / toxicity*
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Calcium / metabolism
  • Carbazoles / administration & dosage
  • Carbazoles / pharmacology*
  • Carvedilol
  • Cisplatin / administration & dosage
  • Cisplatin / toxicity*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / ultrastructure
  • Kidney Diseases / chemically induced
  • Kidney Diseases / metabolism
  • Kidney Diseases / prevention & control*
  • Male
  • Membrane Potentials / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxygen Consumption / drug effects
  • Propanolamines / administration & dosage
  • Propanolamines / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • Antihypertensive Agents
  • Antineoplastic Agents
  • Antioxidants
  • Carbazoles
  • Propanolamines
  • Carvedilol
  • Cisplatin
  • Calcium