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

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.

A clioquinol-containing Pluronic® F127 polymeric micelle system is effective in the treatment of visceral leishmaniasis in a murine model

“…In this context, only five doses were administered. In other studies, higher numbers of doses and concentrations of antileishmanial compounds are usually employed in the animals, aiming to enhance their efficacy [21,36,42]. The results found here indicated a 90% reduction in the parasite load in the treated and infected animals, when compared to the other groups.…”

The combination therapy of meglumine antimoniate and oxiranes (epoxy-α-lapachone and epoxymethyl-lawsone) enhance the leishmanicidal effect in mice infected by Leishmania (Leishmania) amazonensis

“…The tenth week post-infection was settled as the chosen time point for lesion size measurements. Considering that no dose-response pattern was observed for any of the applied dosages of LAW and LAP and that the highest dosage of these compounds elicited significant signs of tissue toxicity (Oliveira et al, 2017a), the intermediate dosage was elected to perform the combination treatment assays.…”

Does Abatacept Induce Testicular Toxicity?

“…However, we have to keep in mind that monitoring for adverse testicular effects in mice in real time presents a challenge because there is a latency period of several weeks between the time of an injury to seminiferous tubules and the time when that injury can be detected using the semen analysis; 7,32-38 in fact, early onset of drug induced gonadal toxicity might appear within days to few weeks. [39][40][41] A limitation of this study includes the lack of assessment of semen and hormonal levels of gonadotropins and testosterone.…”