Increased oxidative stress is correlated with mitochondrial dysfunction in chagasic patients

Jian jun Wen, Pedro C. Yachelini, Adela Sembaj, Rafael E. Manzur, Nisha Jain Garg

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Previously, we have shown in an experimental model of Trypanosoma cruzi infection that increased oxidative stress and antioxidant insufficiency are associated with myocardial (cellular and mitochondrial) oxidative damage and mitochondrial functional decline and might be of pathological significance in Chagas disease. In the present study, we investigated whether enhanced oxidative stress and mitochondrial functional decline are found in human chagasic patients. Our data show substantially higher plasma (two-four-fold) and mitochondrial (67%) malonylaldehyde (MDA) levels in chagasic (n = 80, group 2) compared to healthy (n = 50, group 1) subjects. Moreover, antioxidant defense was compromised in chagasic patients. Hence, we noted a 50% decline in glutathione content and losses of 31, 60, and 68% in glutathione peroxidase, superoxide dismutase (SOD), and MnSOD activities, respectively, relative to the findings in healthy controls. Further, chagasic subjects exhibited decreased mitochondrial respiratory complex (CI: 72%; CIII: 71%) activities. Nonchagasic cardiomyopathy subjects (n = 20, group 3) exhibited marginally higher plasma MDA levels compared to gp1 subjects and were not compromised in plasma antioxidant defense capacity. These data suggest that human chagasic patients sustain an antioxidant/oxidant imbalance and a mitochondrial decline of respiratory complex activities in the circulatory system. A positive correlation between increased MDA levels, MnSOD decline, and inhibition of respiratory complexes suggests that oxidative stress may contribute to mitochondrial dysfunction in chagasic patients.

Original languageEnglish (US)
Pages (from-to)270-276
Number of pages7
JournalFree Radical Biology and Medicine
Volume41
Issue number2
DOIs
StatePublished - Jul 15 2006

Keywords

  • Blood
  • Chagas disease
  • Humans
  • Mitochondria
  • Oxidant/antioxidant status
  • Oxidative stress
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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