MnSOD Mice Control Myocardial Inflammatory and Oxidative Stress and Remodeling Responses Elicited in Chronic Chagas Disease

Methods and Results-—C57BL/6 mice (wild type, MnSOD, MnSOD , GPx1 / ) were infected with Trypanosoma cruzi and harvested during the chronic disease phase. Chronically infected mice exhibited a substantial increase in plasma levels of inflammatory markers (nitric oxide, myeloperoxidase), lactate dehydrogenase, and myocardial levels of inflammatory infiltrate and oxidative adducts (malondialdehyde, carbonyls, 3-nitrotyrosine) in the order of wild type=MnSOD >GPx1 / >MnSOD. Myocardial mitochondrial damage was pronounced and associated with a >50% decline in mitochondrial DNA content in chronically infected wild-type and GPx1 / mice. Imaging of intact heart for cardiomyocytes and collagen by the nonlinear optical microscopy techniques of multiphoton fluorescence/second harmonic generation showed a significant increase in collagen (>10-fold) in chronically infected wild-type mice, whereas GPx1 / mice exhibited a basal increase in collagen that did not change during the chronic phase. Chronically infected MnSOD mice exhibited a marginal decline in mitochondrial DNA content and no changes in collagen signal in the myocardium. P47 / mice lacking phagocyte-generated reactive oxygen species sustained a low level of myocardial oxidative stress and mitochondrial DNA damage in response to Trypanosoma cruzi infection. Yet chronically infected p47 / mice exhibited increase in myocardial inflammatory and remodeling responses, similar to that noted in chronically infected wild-type mice.