title: Mitochondria Superoxide Anion Production Contributes to Geranylgeraniol-Induced Death in Leishmania amazonensis.
abstract: Here we demonstrate the activity of geranylgeraniol, the major bioactive constituent from seeds of Bixa orellana, against Leishmania amazonensis. Geranylgeraniol was identified through (1)H and (13)C nuclear magnetic resonance imaging and DEPT. The compound inhibited the promastigote and intracellular amastigote forms, with IC(50) of 11 ± 1.0 and 17.5 ± 0.7 μg/mL, respectively. This compound was also more toxic to parasites than to macrophages and did not cause lysis in human blood cells. Morphological and ultrastructural changes induced by geranylgeraniol were observed in the protozoan by electronic microscopy and included mainly mitochondria alterations and an abnormal chromatin condensation in the nucleus. These alterations were confirmed by Rh 123 and TUNEL assays. Additionally, geranylgeraniol induces an increase in superoxide anion production. Collectively, our in vitro studies indicate geranylgeraniol as a selective antileishmanial that appears to be mediated by apoptosis-like cell death.
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Laboratório de Inovação Tecnológica no Desenvolvimento de Fármacos e Cosméticos, Bloco B-08, Universidade Estadual de Maringá, Avenida Colombo 5790, 87020-900 Maringá, PR, Brazil.
authors.forename: Milene Valéria
authors.initials: MV
authors.lastname: Lopes
authors.forename: Vânia Cristina
authors.initials: VC
authors.lastname: Desoti
authors.forename: Angelo de Oliveira
authors.initials: Ade O
authors.lastname: Caleare
authors.forename: Tânia
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.forename: Sueli Oliveira
authors.initials: SO
authors.lastname: Silva
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura