TY - JOUR
T1 - Tissue-specific oxidative imbalance and mitochondrial dysfunction during Trypanosoma cruzi infection in mice
AU - Wen, Jian Jun
AU - Dhiman, Monisha
AU - Whorton, Elbert B.
AU - Garg, Nisha Jain
N1 - Funding Information:
This work was supported in part by grants from the John Sealy Memorial Endowment Fund (CON15420) and National Institutes of Health (AI054578). Our thanks are due to Mardelle Susman for editing the manuscript.
PY - 2008/8
Y1 - 2008/8
N2 - 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.
AB - 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.
KW - Chagas' disease
KW - Mitochondrial dysfunction
KW - Oxidant/antioxidant status
KW - Tissue specificity
KW - Trypanosoma cruzi
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U2 - 10.1016/j.micinf.2008.06.013
DO - 10.1016/j.micinf.2008.06.013
M3 - Article
C2 - 18675934
AN - SCOPUS:54049119984
SN - 1286-4579
VL - 10
SP - 1201
EP - 1209
JO - Microbes and Infection
JF - Microbes and Infection
IS - 10-11
ER -