Oxidative damage during chagasic cardiomyopathy development: Role of mitochondrial oxidant release and inefficient antioxidant defense

Jian Jun Wen, Galina Vyatkina, Nisha Garg

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

In this study, we evaluated the oxidant status and antioxidant defense capabilities of the heart during the course of Trypanosoma cruzi infection and disease development in a murine model system. Our data show that the extent of protein carbonylation and lipid peroxidation is increased in the heart, but not the skeletal muscle, of infected mice. The level of oxidative injury biomarkers in the myocardium consistently increased with chronic disease severity. The antioxidant defense constituted by catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GSR), and reduced glutathione was increased in murine heart and skeletal tissue in response to the stress of T. cruzi infection. After the initial burst, CAT, GPx, and GSR remained unresponsive to the severity of chronic tissue damage in chagasic hearts. The cardiac level of Mn 2+ superoxide dismutase (MnSOD) was diminished in chagasic mice. Our data suggest that the host responds to acute injuries by activating antioxidant defenses that are of sufficient magnitude to scavenge the reactive oxidants in skeletal tissue. The myocardia of infected mice, however, sustain increased oxidative injuries with disease progression. We surmise that MnSOD deficiencies, resulting in the increased release of mitochondrial free radicals, lead to sustained oxidative stress that exceeds the cardiac antioxidant defense capacity and contribute to persistent oxidative damage in chagasic myocardium.

Original languageEnglish (US)
Pages (from-to)1821-1833
Number of pages13
JournalFree Radical Biology and Medicine
Volume37
Issue number11
DOIs
StatePublished - Dec 1 2004

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Keywords

  • Antioxidant status
  • Chagasic cardiomyopathy
  • Free radicals
  • Mitochondria
  • Oxidative damage
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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