{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T07:40:21Z","timestamp":1773301221357,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,9,26]],"date-time":"2011-09-26T00:00:00Z","timestamp":1316995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    , the aetiological agent of Chagas disease, invades nucleated mammalian cells including macrophages. In this study, we investigated the crosstalk between\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    \u2010induced immune activation of reactive oxygen species (ROS) and pro\u2010inflammatory responses, and their role in myocardial pathology. Splenocytes of infected mice (C3H\/HeN) responded to\n                    <jats:italic>Tc<\/jats:italic>\n                    \u2010antigenic stimulus by more than a two\u2010fold increase in NADPH oxidase (NOX) activity, ROS generation, cytokine production (IFN\u2010\u03b3 &gt; IL\u20104 &gt; TNF\u03b1 &gt; IL1\u2010\u03b2\u2248 IL6), and predominant expansion of CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Inhibition of NOX, but not of myeloperoxidase and xanthine oxidase, controlled the ROS (&gt;98%) and cytokine (70\u201389%) release by\n                    <jats:italic>Tc<\/jats:italic>\n                    \u2010stimulated splenocytes of infected mice. Treatment of infected mice with apocynin (NOX inhibitor) in drinking water resulted in a 50\u201390% decline in endogenous NOX\/ROS and cytokine levels, and splenic phagocytes' proliferation. The splenic percentage of T cells was maintained, though more than a 40% decline in splenic index (spleen weight\/body weight) indicated decreased T\u2010cell proliferation in apocynin\u2010treated\/infected mice. The blood and tissue parasite burden were significantly increased in apocynin\u2010treated\/infected mice, yet acute myocarditis, ie inflammatory infiltrate consisting of macrophages, neutrophils, and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and tissue oxidative adducts (eg 8\u2010isoprostanes, 3\u2010nitrotyrosine, and 4\u2010hydroxynonenal) were diminished in apocynin\u2010treated\/infected mice. Consequently, hypertrophy (increased cardiomyocytes' size and \u03b2\u2010\n                    <jats:italic>MHC, BNP<\/jats:italic>\n                    , and\n                    <jats:italic>ANP<\/jats:italic>\n                    mRNA levels) and fibrosis (increased collagen, glycosaminoglycans, and lipid contents) of the heart during the chronic phase were controlled in apocynin\u2010treated mice. We conclude that NOX\/ROS is a critical regulator of the splenic response (phagocytes, T cells, and cytokines) to\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    infection, and bystander effects of heart\u2010infiltrating phagocytes and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells resulting in cardiac remodelling in chagasic mice. Copyright \u00a9 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.2975","type":"journal-article","created":{"date-parts":[[2011,7,26]],"date-time":"2011-07-26T10:44:04Z","timestamp":1311677044000},"page":"583-596","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["NADPH oxidase inhibition ameliorates\n                    <i>Trypanosoma cruzi<\/i>\n                    \u2010induced myocarditis during Chagas disease"],"prefix":"10.1002","volume":"225","author":[{"given":"Monisha","family":"Dhiman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nisha 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