Antileishmanial Activity of Niosomal Combination Forms of Tioxolone along with Benzoxonium Chloride against Leishmania tropica

In this study, we carried out extensive in vitro studies on various concentrations of tioxolone along with benzoxonium chloride and their niosomal forms against Leishmania tropica. Niosomes were prepared by the hydration method and were evaluated for morphology, size, release study, and encapsulation efficiency. This study measured leishmanicidal activity against promastigote and amastigote, apoptosis and gene expression levels of free solution and niosomal-encapsulated tioxolone along with benzoxonium chloride. Span/Tween 60 niosome had good physical stability and high encapsulation efficiency (more than 97%). The release profile of the entrapped compound showed that a gradual release rate. The combination of niosomal forms on promastigote and amastigote were more effective than glucantime. Also, the niosomal form of this compound was significantly less toxic than glucantime (P≤0.05). The flowcytometric analysis on niosomal form of drugs showed that higher number of early apoptotic event as the principal mode of action (89.13% in 200 μg/ml). Also, the niosomal compound increased the expression level of IL-12 and metacaspase genes and decreased the expression level of the IL-10 gene, which further confirming the immunomodulatory role as the mechanism of action. We observed the synergistic effects of these 2 drugs that induced the apoptotic pathways and also up regulation of an immunomodulatory role against as the main mode of action. Also, niosomal form of this combination was safe and demonstrated strong anti-leishmaniasis effects highlights further therapeutic approaches against anthroponotic cutaneous leishmaniasis in future planning.

Effects of administration of co-trimoxazole and folic acid on sperm quality and histological changes of testes in male rats

Background: Male infertility has been reported following long-term sulfasalazine, however, the precise effects of co-trimoxazole on sperm quality is controversial

Objective: In this study, we evaluated the effects of co-trimoxazole and its co-administration with folic acid on sperm quality and histological changes of testes in male rats

Materials and Methods: In this experimental study, 136 male Wistar rats were divided into 9 groups: I [control], II [vehicle] received saline, III: received folic acid [1 mg/kg /daily i.p., and IV- IX received co-trimoxazole [30, 60, and 120 mg/kg/daily; i.p.]+folic acid [1 mg/kg/daily; i.p.] for 14 or 28 days. Sperm samples were obtained from each group at the end of 14[th] and 28[th] days. Sperm numbers, motility, and viability were evaluated on a hemocytometer. Hematoxylin and Eosin stained testes were done for evaluation of the number of Leydig cells, vascularity, spermatids, spermatocytes, and means of seminiferous tubules diameter under light microscopy

Results: Co-trimoxazole treatment for either 14 or 28 days caused a significant decrease in the percentage of sperm number, motility, and viability [p<0.001] compared to the control group. Also, high doses of co-trimoxazole caused a significant decrease in testes structural abnormalities means of seminiferous tubules diameter, spermatids, and spermatogonia] compared to the vehicle group [p<0.001]. Folic acid co-administration with co-trimoxazole partially reversed the decrease in sperm quality and structural abnormalities of high doses of co-trimoxazole [60 and 120 mg/kg/daily] [p<0.001]

Conclusion: The data showed the adverse effects of co-trimoxazole on sperm quality and testes morphology which was protected partially by folic acid co-administration in rats. The underlying mechanism [s] needs further investigations