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Trypanocidal Action of (−)-Elatol Involves an Oxidative Stress Triggered by Mitochondria Dysfunction
Postgraduate Program in Pharmaceutical Sciences, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil
Department of Marine Biology, Federal Fluminense University, PO Box 100644, CEP 24001-970, Niteroi, Rio de Janeiro, Brazil
Institute of Physics, Federal University of Goias, CEP 74001-970, Goiania, Goias, Brazil
Department of Basic Health Sciences, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil
* Author to whom correspondence should be addressed.
Received: 22 June 2012; in revised form: 8 July 2012 / Accepted: 27 July 2012 / Published: 3 August 2012
Abstract: Natural compounds have shown good potential for the discovery of new chemotherapeutics for the treatment of Chagas’ disease. Recently, our group reported the effective trypanocidal activity of (−)-elatol, extracted from the red macroalgae Laurencia dendroidea present in the Brazilian coast against Trypanosoma cruzi. However, the mechanism of action of this compound has remained unclear. There are only hypotheses concerning its action on mitochondrial function. Here, we further investigated the mechanisms of action of (−)-elatol on trypomastigotes of T. cruzi. For this, we evaluated some biochemical alterations in trypomastigotes treated with (−)-elatol. Our results show that (−)-elatol induced depolarization of the mitochondrial membrane, an increase in the formation of mitochondrial superoxide anion and loss of cell membrane and DNA integrity. Additionally, (−)-elatol induced formation of autophagic vacuoles and a decrease in cell volume. All together, these results suggest that the trypanocidal action of (−)-elatol involves multiple events and mitochondria might be the initial target organelle. Our hypothesis is that the mitochondrial dysfunction leads to an increase of ROS production through the electron transport chain, which affects cell membrane and DNA integrity leading to different types of parasite death.
Keywords: (−)-elatol; Trypanosoma cruzi; Chagas’ disease; mitochondria; oxidative stress
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Desoti, V.C.; Lazarin-Bidóia, D.; Sudatti, D.B.; Pereira, R.C.; Alonso, A.; Ueda-Nakamura, T.; Dias Filho, B.P.; Nakamura, C.V.; de Oliveira Silva, S. Trypanocidal Action of (−)-Elatol Involves an Oxidative Stress Triggered by Mitochondria Dysfunction. Mar. Drugs 2012, 10, 1631-1646.
Desoti VC, Lazarin-Bidóia D, Sudatti DB, Pereira RC, Alonso A, Ueda-Nakamura T, Dias Filho BP, Nakamura CV, de Oliveira Silva S. Trypanocidal Action of (−)-Elatol Involves an Oxidative Stress Triggered by Mitochondria Dysfunction. Marine Drugs. 2012; 10(8):1631-1646.
Desoti, Vânia Cristina; Lazarin-Bidóia, Danielle; Sudatti, Daniela Bueno; Pereira, Renato Crespo; Alonso, Antonio; Ueda-Nakamura, Tania; Dias Filho, Benedito Prado; Nakamura, Celso Vataru; de Oliveira Silva, Sueli. 2012. "Trypanocidal Action of (−)-Elatol Involves an Oxidative Stress Triggered by Mitochondria Dysfunction." Mar. Drugs 10, no. 8: 1631-1646.