Peroxynitrite-mediated cytotoxicity to Trypanosoma cruzi.

摘要: Macrophages produce and release superoxide anion (O.−2) nitric oxide (.NO) as part of their microbicidal effector molecules. The simultaneous production O2.− .NO results in the rapid formation peroxynitrite (ONOO−) by macrophages. Peroxynitrite is a strong oxidant with half-life less than 1 s biological systems. There solid experimental evidence implicating O.−2 macrophage-induced cytotoxicity against bacteria, parasites, tumor cells. However, cytotoxic role these processes remains to be studied. In this work we demonstrate parasiticidal activity ONOO− Trypanosoma cruzi. was highly trypanocidal, killing T. cruzi dose-dependent manner. Addition 500 μM single bolus resulted 50% inhibition cell proliferation followed growth curves. Fifty percent [3H]thymidine incorporation measured at 6 h postaddition obtained 150 μM. continuous infusion rather an even stronger growth. Other effects included cellular swelling motility. Classical hydroxyl radical scavengers metal chelators afforded minimal protection ONOO−-mediated cytotoxicity, indicating that itself, .OH-like derived from its proton-catalyzed decomposition, main damaging species. From literature data estimated activated macrophages inside phagolysosomes around μM/min. Therefore, our may operate vivo critical macrophage-derived reactive intermediate T.cruzi.