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BioMed Research International
Volume 2017 (2017), Article ID 9840210, 11 pages
https://doi.org/10.1155/2017/9840210
Research Article

Evidence for Tissue Toxicity in BALB/c Exposed to a Long-Term Treatment with Oxiranes Compared to Meglumine Antimoniate

1Laboratório de Biologia Molecular e Doenças Endêmicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Avenida Brasil 4365, Manguinhos, 21040-900 Rio de Janeiro, RJ, Brazil
2Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Avenida Brasil 4365, Manguinhos, 21040-900 Rio de Janeiro, RJ, Brazil
3Laboratório de Ultraestrutura e Biologia Tecidual, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Boulevard 28 de Setembro, No. 87, Vila Isabel, 20551-030 Rio de Janeiro, RJ, Brazil
4Laboratório de Tecnologia Virológica, Instituto de Tecnologia em Imunobiológicos, Fundação Oswaldo Cruz (Fiocruz), Avenida Brasil 4365, Manguinhos, 21040-900 Rio de Janeiro, RJ, Brazil
5Instituto de Biologia, Universidade Federal Fluminense, Outeiro São João Batista S/N, 24210-130 Niterói, RJ, Brazil
6Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Outeiro São João Batista S/N, Centro, 24210-130 Niterói, RJ, Brazil
7Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Avenida Brasil 4365, Manguinhos, 21040-900 Rio de Janeiro, RJ, Brazil

Correspondence should be addressed to Carlos Roberto Alves; rb.zurcoif.coi@sevlac

Received 3 March 2017; Revised 19 May 2017; Accepted 1 June 2017; Published 17 July 2017

Academic Editor: Philippe Holzmuller

Copyright © 2017 Luiz Filipe Gonçalves Oliveira et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Leishmaniasis remains a serious public health problem in developing countries without effective control, whether by vaccination or chemotherapy. Part of the failure of leishmaniasis control is due to the lack of new less toxic and more effective drugs able to eliminate both the lesions and the parasite. Oxiranes derived from naphthoquinones now being assayed are promising drugs for the treatment of this group of diseases. The predicted pharmacokinetic properties and toxicological profiles of epoxy-α-lapachone and epoxymethoxy-lawsone have now been compared to those of meglumine antimoniate, and histological changes induced by these drugs in noninfected BALB/c mice tissues are described. Effects of these compounds on liver, kidney, lung, heart, and cerebral tissues of healthy mice were examined. The data presented show that both these oxiranes and meglumine antimoniate induce changes in all BALB/c mice tissues, with the lung, heart, and brain being the most affected. Epoxymethoxy-lawsone was the most toxic to lung tissue, while most severe damage was caused in the heart by epoxy-α-lapachone. Meglumine antimoniate caused mild-to-moderate changes in heart and lung tissues.