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DOI: 10.1055/s-0033-1351831
Oxidative stress induced by (-)-elatol leads to autophagic death in amastigote forms of Trypanosoma cruzi
Chagas' disease, a neglected disease, is caused by the parasite Trypanosoma cruzi. The currently drugs available for the treatment of this disease are unsatisfactory, making the search for new chemotherapeutic agents a priority [1, 2]. Recently we described the trypanocidal action of (-)-elatol, extracted from macroalgae Laurencia dendroidea [3]. However, nothing was described about the mechanism of action of this compound on amastigotes that are involved in the chronic phase of Chagas' disease. Thus, this study evaluated the effect of (-)-elatol on formation of superoxide anion (O2 ·–), DNA fragmentation and autophagy in amastigotes of T. cruzi. Amastigotes were loaded with MitoSOX and then washed with Krebs-Henseleit buffer before the assays. The formation of O2 ·– was evaluated during the exposure of amastigotes to 3, 15, 30 and 150µM of (-)-elatol and after different times (0, 1, 2 and 3h) of incubation the fluorescence was measured by fluorimetry. Amastigotes were also treated with 1.5 and 3µM of (-)-elatol for 24h and labeled with TUNEL to measure DNA fragmentation or incubated with monodansylcadaverine to determine autophagic vacuoles using fluorescence microscope. The treatment of amastigotes with (-)-elatol induced increase in the formation of O2 ·– in all concentrations of (-)-elatol assayed, unlike the untreated parasites. Additionally, an increase of fluorescence was observed in treated parasites with (-)-elatol indicating DNA fragmentation and formation of autophagic vacuoles. It is possible to suppose that the trypanocidal action of (-)-elatol might induce autophagic death pathway triggered by an imbalance of the parasite redox metabolism.
References:
[1] E. Izumi, et al., Experimental Parasitology, 118 (2008) 324 – 330.
[2] P., Veiga-Santos et al., Parasitology, 137 (2010) 1661 – 1670.
[3] V. C., Desoti et al., Marine Drugs, 10 (2012) 1631 – 1646, 2012.
Acknowledgements: This study was supported through grants from CNPq, Fundação Araucária, FINEP, and CAPES.