title: Leishmania amazonensis: effects of oral treatment with copaiba oil in mice.
abstract: Leishmaniasis is a severe public-health problem, with high rates of morbidity and mortality. Efforts to find new, effective and safe oral agents for the treatment of leishmaniasis have been ongoing for several decades, in order to avoid the problems with the currently used antimonials. In the present study, we found that a copaiba oil oral treatment (Group IV) caused a significant reduction in the average lesion size (1.1±0.4mm) against Leishmania amazonensis lesions compared with untreated mice (Group I) (4.4±1.3mm). To prove the safety of the oil, the toxicity and genotoxicity were also determined. Histopathological evaluation did not reveal changes in the copaiba oil-treated animals compared to the control animals. In the mutagenicity evaluation, (micronucleus test) the dose tested (2000mg/kg) showed no genotoxic effects. Morphological and ultrastructural analyses demonstrated notable changes in parasite cells treated with this oleoresin. The main ultrastructural effect was mitochondrial swelling. We also demonstrated that in vitro copaiba oil treatment of L. amazonensis led to an increase in plasma membrane permeability, and depolarization in the mitochondrial membrane potential in parasite cells. Although the mechanism of action of the oleoresin is still unclear, these findings indicate that copaiba oil is a possible new drug, which would provide a safer, shorter, less-expensive, and more easily administered treatment for leishmaniasis.
authors.affiliation: Programa de Pós-graduação em Microbiologia, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid, PR 445, Km 380, CEP 86051-990, Londrina, Paraná, Brazil.
authors.forename: Adriana Oliveira
authors.initials: AO
authors.lastname: dos Santos
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Costa
authors.forename: Tânia
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.forename: Benedito Prado
authors.initials: BP
authors.lastname: Dias-Filho
authors.forename: Valdir Florêncio
authors.initials: VF
authors.lastname: da Veiga-Júnior
authors.forename: Marli Miriam
authors.initials: MM
authors.lastname: de Souza Lima
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D007887:Fabaceae / Q000737:chemistry*; D005434:Flow Cytometry; D006801:Humans; D007279:Injections, Subcutaneous; D007894:Leishmania mexicana / Q000187:drug effects* / Q000648:ultrastructure; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000077485:Meglumine Antimoniate; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D015162:Micronucleus Tests; D008855:Microscopy, Electron, Scanning; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009153:Mutagens / Q000008:administration & dosage / Q000494:pharmacology; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010938:Plant Oils / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000981:Antiprotozoal Agents; D009153:Mutagens; D009942:Organometallic Compounds; D010938:Plant Oils; D008536:Meglumine; D000077485:Meglumine Antimoniate; D003520:Cyclophosphamide