title: Trypanocidal action of (-)-elatol involves an oxidative stress triggered by mitochondria dysfunction.
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.
authors.affiliation: Postgraduate Program in Pharmaceutical Sciences, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil.
authors.forename: Vânia Cristina
authors.initials: VC
authors.lastname: Desoti
authors.affiliation: Postgraduate Program in Pharmaceutical Sciences, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil.
authors.forename: Danielle
authors.initials: D
authors.lastname: Lazarin-Bidóia
authors.affiliation: Department of Marine Biology, Federal Fluminense University, PO Box 100644, CEP 24001-970, Niteroi, Rio de Janeiro, Brazil.
authors.forename: Daniela Bueno
authors.initials: DB
authors.lastname: Sudatti
authors.affiliation: Department of Marine Biology, Federal Fluminense University, PO Box 100644, CEP 24001-970, Niteroi, Rio de Janeiro, Brazil.
authors.forename: Renato Crespo
authors.initials: RC
authors.lastname: Pereira
authors.affiliation: Institute of Physics, Federal University of Goias, CEP 74001-970, Goiania, Goias, Brazil.
authors.forename: Antonio
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Postgraduate Program in Pharmaceutical Sciences, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil.|Department of Basic Health Sciences, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil.
authors.forename: Tania
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.affiliation: Postgraduate Program in Pharmaceutical Sciences, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil.|Department of Basic Health Sciences, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil.
authors.forename: Benedito Prado
authors.initials: BP
authors.lastname: Dias Filho
authors.affiliation: Postgraduate Program in Pharmaceutical Sciences, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil.|Department of Basic Health Sciences, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil.
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura
authors.affiliation: Postgraduate Program in Pharmaceutical Sciences, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil.|Department of Basic Health Sciences, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil.
authors.forename: Sueli
authors.initials: S
authors.lastname: De Oliveira Silva
mesh_terms: D001343:Autophagy / Q000187:drug effects; D001938:Brazil; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D014355:Chagas Disease / Q000188:drug therapy; D016054:DNA, Protozoan / Q000187:drug effects; D044722:Laurencia / Q000737:chemistry; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D051336:Mitochondrial Membranes / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013141:Spiro Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014617:Vacuoles / Q000187:drug effects
chemical_list: D016054:DNA, Protozoan; D017382:Reactive Oxygen Species; D013141:Spiro Compounds; D014344:Trypanocidal Agents; C485576:elatol