Carvedilol protects tubular epithelial cells from ischemia-reperfusion injury by inhibiting oxidative stress

Int J Urol. 2010 Dec;17(12):989-95. doi: 10.1111/j.1442-2042.2010.02644.x. Epub 2010 Oct 14.

Abstract

Objectives: Renal ischemia-reperfusion injury (IRI), leading to acute kidney injury, is a frequent complication with renal transplantation and it is associated with graft function. Its pathogenesis involves ischemia, vascular congestion and reactive oxygen metabolites. Carvedilol is an antihypertensive drug with potent anti-oxidant properties. In this study we investigated the protective effects of carvedilol in a rat renal IRI model.

Methods: Twenty-four rats were randomized into sham, untreated control and carvedilol (2 mg/kg 30 min before surgery and 12 hr after reperfusion) treatment groups and were subjected to 60 min of left renal ischemia followed by reperfusion at 24, 48, 96 and 168 hr.

Results: Treatment with carvedilol significantly decreased plasma creatinine levels after IRI (up to 168 hr) compared to controls (P < 0.001), suggesting an improvement in renal function. Histopathological analysis revealed decreased IRI-induced damage in kidneys from carvedilol-treated rats. A significant increase in the expression levels of Cu/Zn superoxide dismutase and reduction of 8-hydroxydeoxyguanosine and apoptosis levels (P < 0.005) suggested a protective effect after treatment with carvedilol.

Conclusions: Our findings suggest that carvedilol ameliorates IRI resulting in improved renal function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Apoptosis / drug effects
  • Carbazoles / pharmacology*
  • Carvedilol
  • Creatinine / blood
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Disease Models, Animal
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Kidney Tubules / cytology
  • Kidney Tubules / drug effects*
  • Kidney Tubules / metabolism
  • Male
  • Oxidative Stress / drug effects*
  • Propanolamines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Renal Insufficiency / prevention & control*
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Superoxide Dismutase / metabolism

Substances

  • Antihypertensive Agents
  • Carbazoles
  • Propanolamines
  • Carvedilol
  • 8-Hydroxy-2'-Deoxyguanosine
  • Creatinine
  • Superoxide Dismutase
  • Deoxyguanosine