Tissue-specific oxidative imbalance and mitochondrial dysfunction during Trypanosoma cruzi infection in mice.
In this study, we examined the tissue specificity of inflammatory and oxidative responses and mitochondrial dysfunction in mice infected by Trypanosoma cruzi. In acute mice, parasite burden and associated inflammatory infiltrate was detected in all tissues (skeletal muscle>heart>stomach>colon). The extent of oxidative damage and mitochondrial decay was in the order of heart>stomach>skeletal muscle>colon. In chronic mice, a low level of parasite burden and inflammation continued in all tissues; however, oxidant overload and mitochondrial inefficiency mainly persisted in the heart tissue (also detectable in stomach). Further, we noted an unvaryingly high degree of oxidative stress, compromised antioxidant status, and decreased mitochondrial respiratory complex activities in peripheral blood of infected mice. A pair-wise log analysis showed a strong positive correlation in the heart-versus-blood (but not other tissues) levels of oxidative stress markers (malonyldialdehyde, glutathione disulfide), antioxidants (superoxide dismutase, MnSOD, catalase), and mitochondrial inhibition of respiratory complexes (CI/CIII) in infected mice. T. cruzi-induced acute inflammatory and oxidative responses are widespread in different muscle tissues. Antioxidant/oxidant status and mitochondrial function are consistently attenuated in the heart, and reflected in the peripheral-blood of T. cruzi-infected mice. Our results provide an impetus to investigate the peripheral-blood oxidative responses in relation to clinical severity of heart disease in chagasic human patients.
Wen
Jian-Jun
JJ
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Dhiman
Monisha
M
Whorton
Elbert B
EB
Garg
Nisha Jain
NJ
D000818:Animals; D002374:Catalase / Q000378:metabolism; D014355:Chagas Disease / Q000378:metabolism* / Q000469:parasitology; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000502:physiology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism
C478189:respiratory complex II; C002744:3-nitrotyrosine; D014443:Tyrosine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D042963:Electron Transport Complex II; D042967:Electron Transport Complex I