Leishmania amazonensis: Effects of oral treatment with copaiba oil in mice

https://doi.org/10.1016/j.exppara.2011.06.016Get rights and content
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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 ± 0.4 mm) against Leishmania amazonensis lesions compared with untreated mice (Group I) (4.4 ± 1.3 mm). 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 (2000 mg/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.

Highlights

► Copaiba oil oral treatment caused a significant reduction in the lesion size in mice. ► We demonstrated that copaiba oil not showed toxicity and genotoxicity. ► Parasite cells had morphological and ultrastructural changes. ► We showed alterations in plasma membrane permeability of parasite. ► Depolarization in the mitochondrial membrane potential after copaiba oil treatment.

Keywords

Leishmania amazonensis
Copaifera martii
Antileishmanial activity
Experimental treatment

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Adriana Oliveira dos Santos obtained her B.Sc. degree in Biological Sciences in 2005 from the Universidade Estadual de Maringá, Brazil. Currently she is a microbiology Ph.D. student under the supervision of Professor Nakamura from the Universidade Estadual de Londrina, Brazil, where she is studying biological activity of medicinal plants from the Amazon rainforest, against protozoan parasites. Her research interests are natural products and their application to neglected diseases.

Marco Antonio Costa graduated in Pharmacy and Biochemistry at the Universidade Estadual de Maringá, Brazil, in 1990. Currently, he is a microbiology Ph.D. student under the supervision of Professor Nakamura at the same university, where he is studying biological activity of medicinal plants, against Candida sp. Too currently he is an Assistant Professor at the Universidade Estadual do Oeste do Paraná, and his research interests are antimicrobial activity of natural products, focusing on antifungal activity.

Tania Ueda-Nakamura obtained her B.Sc. degree in Pharmacy and Biochemistry in 1980 from the Universidade Estadual de Maringá, Brazil. In 2001, she received her Ph.D. degree in Biophysics from the Universidade Federal do Rio de Janeiro, and she undertook postdoctoral research on CERMAV – France, and currently she is an Associate Professor of the Universidade Estadual de Maringá. Her research interests are antiviral and antiprotozoal activities of natural products.

Benedito Prado Dias Filho received his B.Sc. degree in Pharmacy and Biochemistry in 1973, from the Universidade Estadual de Ponta Grossa, Brazil, and in 1992, he obtained his Ph.D. degree in Microbiology from the Universidade Federal do Rio de Janeiro. Currently, he is a Full Professor of the Universidade Estadual de Maringá. His main interests are nanotechnology and antimicrobial activity of natural products, focusing on dermatophytes.

Valdir Florêncio da Veiga Júnior obtained his B.Sc. degree in Chemical Engineering in 1995 and the Ph.D. degree in Chemistry in 2004 from the Universidade Federal do Rio de Janeiro, Brazil. Currently, he is an Associate Professor of the Universidade Federal do Amazonas. His research interests are the chemistry of natural products, focusing on medicinal plants of the families Fabaceae, Burseraceae, and Lauraceae.

Marli Miriam de Souza Lima is graduated in Pharmacy at the Universidade Estadual de Maringá, Brazil, in 1989. She obtained her Ph.D. degree in Polymer Physico-Chemistry at the Université de Bordeaux I, France in 2002. She is currently professor at the Universidade Estadual de Maringá in the department of Pharmacy. Her research line is the development of drug release systems biopolymer-based and it physico chemistry caracterisation.

Celso Vataru Nakamura graduated in Pharmacy and Biochemistry at the Universidade Estadual de Maringá, Brazil, in 1979. He obtained his Ph.D. degree in Microbiology at the Universidade Federal do Rio de Janeiro in 1992, and he undertook postdoctoral research on Biophysics, working with ultrastructural analysis of cellular organelles from parasitic protozoa. Currently he is an Associate Professor at the Universidade Estadual de Maringá, and his research interests are the development of new drugs from natural sources, focusing on antimicrobial, antiprotozoal, and melanogenic activities.