Resveratrol attenuates azidothymidine-induced cardiotoxicity by decreasing mitochondrial reactive oxygen species generation in human cardiomyocytes

Rachel Yue Gao, Partha Mukhopadhyay, Rajesh Mohanraj, Hua Wang, Béla Horváth, Shi Yin, Pál Pacher

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Nucleotide reverse transcriptase inhibitors, such as zidovudine (azidothymidine, AZT) and stavudine, represent a class of approved antiretroviral agents for highly active antiretroviral therapy, which prolongs the life expectancy of patients infected with human-immunodeficiency virus. Unfortunately, the use of these drugs is associated with known toxicities in the liver, skeletal muscle, heart and other organs, which may involve increased reactive oxygen species (ROS) generation, among other mechanisms. Resveratrol is a polyphenolic plant-derived antioxidant abundantly found in certain grapes, roots, berries, peanuts and red wine. This study, using primary human cardiomyocytes, evaluated the effects of AZT and pre-treatment with resveratrol on mitochondrial ROS generation and the cell death pathways. AZT induced concentration-dependent cell death, involving both caspase-3 and -7 and poly(ADP-ribose) polymerase activation, coupled with increased mitochondrial ROS generation in human cardiomyocytes. These effects of AZT on mitochondrial ROS generation and cell death may be attenuated by resveratrol pre-treatment. The results demonstrate that mitochondrial ROS generation plays a pivotal role in the cardiotoxicity of AZT in human cardiomyocytes, and resveratrol may provide a potential strategy to attenuate these pathological alterations, which are associated with widely used antiretroviral therapy.

Original languageEnglish
Pages (from-to)151-155
Number of pages5
JournalMolecular Medicine Reports
Volume4
Issue number1
DOIs
Publication statusPublished - Jan 2011
Externally publishedYes

Keywords

  • Azidothymidine
  • Cardiomyocytes
  • Cell death
  • Reactive oxygen species
  • Resveratrol

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

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