Alagebrium chloride protects the heart against oxidative stress in aging rats

J Gerontol A Biol Sci Med Sci. 2009 Jun;64(6):629-35. doi: 10.1093/gerona/glp023. Epub 2009 Mar 18.

Abstract

To investigate the possible effects of alagebrium chloride (ALT-711) on oxidative stress (OS) process in aging hearts, we examined the role of ALT-711 in cardiac function and OS in the heart of aging rats. Increased mitochondrial DNA (mtDNA) deletion as well as nearly a twofold increase in advanced glycation end products (AGEs) accumulation were observed in aging heart, whereas only about 50% of the superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were seen. However, after treatment with ALT-711, preserved cardiac diastolic function accompanied with reduced mtDNA deletion and about 30% of AGEs decrease was observed in aging hearts. In addition, ALT-711 can increase SOD and GSH-PX activities in aging hearts as well as in cultured cardiomyocytes. In conclusion, our study suggests that AGEs accumulation and the abnormalities in the OS in aging hearts can be attenuated by ALT-711, and this might be a novel underlying mechanism for ALT-711 in the treatment of cardiovascular diseases that develop with aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects*
  • Animals
  • DNA, Mitochondrial / drug effects
  • DNA, Mitochondrial / metabolism
  • Echocardiography
  • Female
  • Glutathione Peroxidase / drug effects
  • Glutathione Peroxidase / metabolism
  • Glycation End Products, Advanced / metabolism
  • Heart / drug effects*
  • Heart / physiology*
  • Myocardium / pathology
  • Oxidative Stress / drug effects*
  • Protective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / drug effects
  • Superoxide Dismutase / metabolism
  • Thiazoles / pharmacology*

Substances

  • DNA, Mitochondrial
  • Glycation End Products, Advanced
  • Protective Agents
  • Thiazoles
  • alagebrium
  • Glutathione Peroxidase
  • Superoxide Dismutase