title: Trypanocidal action of eupomatenoid-5 is related to mitochondrion dysfunction and oxidative damage in Trypanosoma cruzi.
abstract: Because of its severe side effects and variable efficacy, the current treatment for Chagas disease is unsatisfactory. Natural compounds are good alternative chemotherapeutic agents for the treatment of this infection. Recently, our group reported the antiproliferative activity and morphological alterations in epimastigotes and intracellular amastigotes of Trypanosoma cruzi treated with eupomatenoid-5, a neolignan isolated from leaves of Piper regnellii var. pallescens. Here, we demonstrate that eupomatenoid-5 exhibited activity against trypomastigotes, the infective form of T. cruzi (EC₅₀ 40.5 μM), leading to ultrastructural alteration and lipoperoxidation in the cell membrane. Additionally, eupomatenoid-5 induced depolarization of the mitochondrial membrane, lipoperoxidation and increased G6PD activity in epimastigotes of T. cruzi. These findings support the possibility that different mechanisms may be targeted, according to the form of the parasite, and that the plasma membrane and mitochondria are the structures that are most affected in trypomastigotes and epimastigotes, respectively. Thus, the trypanocidal action of eupomatenoid-5 may be associated with mitochondrial dysfunction and oxidative damage, which can trigger destructive effects on biological molecules of T. cruzi, leading to parasite death.
authors.affiliation: Programa de Pós-graduação em Microbiologia, Universidade Estadual de Londrina, Londrina, Pr, Brazil.
authors.forename: Karin Juliane
authors.initials: KJ
authors.lastname: Pelizzaro-Rocha
authors.forename: Phercyles
authors.initials: P
authors.lastname: Veiga-Santos
authors.forename: Danielle
authors.initials: D
authors.lastname: Lazarin-Bidóia
authors.forename: Tania
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.forename: Benedito Prado
authors.initials: BP
authors.lastname: Dias Filho
authors.forename: Valdecir Farias
authors.initials: VF
authors.lastname: Ximenes
authors.forename: Sueli Oliveira
authors.initials: SO
authors.lastname: Silva
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura
mesh_terms: D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014355:Chagas Disease / Q000188:drug therapy / Q000469:parasitology; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010734:Phosphogluconate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D031701:Piper / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry; D014344:Trypanocidal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D001572:Benzofurans; D017705:Lignans; D010636:Phenols; D010936:Plant Extracts; D014344:Trypanocidal Agents; C452811:eupomatenoid 5; D019298:Glucose-6-Phosphate; D006861:Hydrogen Peroxide; D010734:Phosphogluconate Dehydrogenase