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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access originally published online on March 18, 2009
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2009 64A(6):629-635; doi:10.1093/gerona/glp023
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© The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Alagebrium Chloride Protects the Heart Against Oxidative Stress in Aging Rats

Yan Guo, Miao Lu, Jin Qian and Yun-lin Cheng

Department of Gerontology, First Affiliated Hospital to Nanjing Medical University, China

Address correspondence to Yan Guo, PhD, Department of Gerontology, First Affiliated Hospital to Nanjing Medical University, Nanjing 210029, China. Email: guoyan51{at}hotmail.com


  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.

Keywords Advanced glycation end products (AGEs); Alagebrium chloride (ALT-711); Oxidative stress; Aging heart

Received: September 30, 2008; Accepted: February 6, 2009

Decision Editor: Huber R. Warner, PhD


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