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

与长期使用葡甲胺锑酸盐相比,长期使用环氧乙烷治疗对 BALB/c 小鼠组织毒性的证据

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作者:Luiz Filipe Gonçalves Oliveira, Franklin Souza-Silva, Léa Cysne-Finkelstein, Kíssila Rabelo, Juliana Fernandes Amorim, Adriana de Souza Azevedo, Saulo Cabral Bourguignon, Vitor Francisco Ferreira, Marciano Viana Paes, Carlos Roberto Alves

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.

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