Effects of melatonin on thymic and oxidative stress dysfunctions during Trypanosoma cruzi infection

Abstract

Although the exact etiology of Chagas disease is not completely elucidated, thymic atrophy and oxidative stress are believed to be important contributors to the pathogenesis during acute Trypanosoma cruzi (T. cruzi) infection. We hypothesized that exogenous melatonin, administered by gavage (5 mg/kg, p.o., gavage) to young (5 weeks old) and middle-aged (18 months old) male Wistar rats, would modulate thymic oxidative damage and reverse the age-related thymus regression during T. cruzi acute infection. Increased levels of superoxide anion (O ) were detected in the thymus of infected animals, and treatment with melatonin reverted this response. We found reduced TBARS levels as well as a significant increase in superoxide dismutase (SOD) activity in the thymus of all middle-aged melatonin-treated animals, infected or not with T. cruzi. Furthermore, melatonin increased the thymic expression of SOD1 and SOD2 in middle-aged control animals. Nox2 expression was not affected by melatonin treatment in young or middle-aged animals. Melatonin reverted the age-related thymic regression as revealed by the increase in thymus weight, total number of thymocytes, and reduction in age-related accumulation of double-negative thymocytes. This is the first report to directly examine the effects of melatonin treatment on the thymic antioxidant/oxidant status and thymic changes during T. cruzi infection. Our results revealed new antioxidant features that turn melatonin a potentially useful compound for the treatment of Chagas disease, a condition in which an excessive oxidative damage occurs.

Melatonin in macrophage biology: Current understanding and future perspectives

“…257 The protective role of melatonin is not restricted to macrophages, but has also to be seen in the context of effects on other immune cells, such as T lymphocytes and thymocytes. 258,259 Overall, these convincing results exhibit the beneficial effects of melatonin on macrophage-associated diseases by regulating macrophage responses (Table 2). However, the regulation of melatonin in other macrophage-associated diseases, such as obesity, still needs further detailed investigation.…”

“…Moreover, numbers of peritoneal macrophages were decreased, however, to levels much below those of uninfected controls . The protective role of melatonin is not restricted to macrophages, but has also to be seen in the context of effects on other immune cells, such as T lymphocytes and thymocytes …”

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