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This study aimed to investigate the in vitro and in silico antileishmanial activity of azacitidine (AZA) on Leishmania major promastigotes and amastigotes. The in silico method was used to evaluate the possibility of the interaction of AZA into the binding pocket of inducible nitric oxide synthase (iNOS), a leading defensive oxidative metabolite. Following that, in vitro anti-promastigote, and anti-amastigote activity of AZA was determined using an MTT assay and a macrophage model, respectively. Cytotoxic effects of AZA and meglumine antimoniate (MA) were also assessed by MTT assay on murine macrophages. All experiments were performed in triplicate. The results showed that AZA interacted with Ser133, Gln134, and Lys13 amino acids of iNOS, and the molecular docking score was obtained at -241.053 kcal/mol. AZA in combination with MA significantly (P<0.001) inhibited the growth rate of nonclinical promastigote (IC50 247.6±7.3 μM) and 8.5-fold higher of clinical intramacrophage amastigote stage (29.8±5.3 μM), compared to the untreated group. A significant upsurge of Th1 subsets and transcription genes and a meaningful decline in Th2 cytokines subclasses at the equivalent concentrations of AZA and MA was observed (P<0.001). The apoptosis effect of AZA along with MA was significantly induced on L. major in a dose-dependent manner (P<0.001). The present study demonstrated that AZA possesses antileishmanial activity in in vitro and in silico models. However, AZA combined with MA was more effective than AZA alone in inhibiting the growth rate of promastigotes and amastigotes of L. major. This study indicates that AZA in combination with MA demonstrated a potent antileishmanial mechanism, promoting immune response and enhancing an immunomodulatory role toward the Th1 pathway. This experimental study is a basic study for applying more knowledge about the mechanisms of AZA along with MA in animal models in the future. [ABSTRACT FROM AUTHOR]

Toll‐like receptors (TLRs) and inflammasomes belong to the pattern recognition receptors (PRRs) of innate immunity identifying conserved compounds produced by pathogens or discharged by injured cells. Different cell subsets in the human urogenital system, such as epithelial cells and infiltrating leukocytes, express different kinds of TLRs (such as TLR2, TLR3, TLR4, TLR5 and TLR9) as well as inflammasomes (such as NLRP3, NLRC4 and AIM2). Various types of the Trichomonas vaginalis‐derived components such as glycosyl‐phosphatidylinositol (GPI), T. vaginalis virus (TVV), Lipophosphoglycan (LPG) and flagellin can be recognized by TLR2, TLR3, TLR4 and TLR5, respectively, leading to the production of proinflammatory cytokines and chemokines in the cervicovaginal mucosa. The T. vaginalis‐induced inflammasomes can lead to pyroptosis as well as the release of IL‐1β and IL‐18 promoting innate and adaptive immune responses. The PRR‐mediated responses to T. vaginalis may contribute to the induction of protective immune responses, local inflammation, promotion of co‐infections, or even the development of malignancies, for example, prostate cancer. The protective or pathogenic roles of the TLRs and inflammasomes during trichomoniasis are highlighted in this review. A better understanding of PRR‐mediated responses provides invaluable insights to develop effective immunotherapeutic strategies against T. vaginalis infection. [ABSTRACT FROM AUTHOR]

Background: Methamphetamine (METH) is a widely addictive and abused psychostimulant drug that affects organs of body. In this study, the effects of METH administration for 7, 14, and 28 days on the histological and functional changes of the liver and pancreas of adult male rats were investigated. Methods: In this experimental study, 58 adult male Wistar rats were randomly divided into seven groups including control (received no treatment), vehicle (received saline for 7, 14, and 28 days), and METH (received METH with a dose of 5 ml/kg, IP for 7, 14 or 28 days). Sampling from the liver and pancreas tissues was done after the above-mentioned times for each group, then, tissue samples were stained by H&E technique and evaluated for structural changes, as well as the evaluation of biochemical factors including SGPT, SGOT, and amylase enzymes. Data were analyzed by one-way ANOVA, using SPSS software version 20. Statistical significant level was considered at P<0.05. Results: In this study, METH caused a significant structural change in the liver and pancreas in the METH-treated groups compared with the control group. Functional changes depended on the length of treatment, with the 7-day treatment group having less damage than the 14- and 28-day periods. Conclusion: According to the results of the present study, methamphetamine administration for 7, 14, and 28 days had adverse effects on the rats liver and pancreas structure and their enzymes (SGPT, SGOT, and amylase). Therefore, underlying mechanism need further investigation. [ABSTRACT FROM AUTHOR]

Background: There is an increasing concern over acute exposure of amphetamine and its derivative such as 3,4-methylenedioxymethamphetamine (MDMA) on male reproductive toxicity. Supplementary vitamins can reduce the oxidative stresses and repair the damages on reproductive organs. This experimental study was conducted to evaluate the effects of folic acid (FA) on reproductive indices, the antioxidant enzyme activities, and histological changes of testis on adult male rats treated by MDMA. Methods: This experimental study was conducted on adult male Wistar rats. Animals were divided into 4 groups: control, MDMA, FA, and MDMA + FA. Animals received a dose of 10 mg/kg of MDMA and 1 mg/kg of FA for 7 or 14 days. Rats were anesthetized and sperm quality parameters (number, concentration, motility, and morphology), spermatogenesis indices [the mean seminiferous tubule diameter (MSTD), spermiogenesis index (SI), repopulation index (RI), and tubular differentiation index (TDI)], changes on testicular structure, antioxidant enzyme activities of catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) beside serum level of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were measured. Data were analyzed, using the one-way analysis of variance (ANOVA) and SPSS software. Findings: MDMA (both 7 and 14 days) caused significant changes in sperm quality (P < 0.001), spermatogenesis indices (P < 0.001), testicular histopathology, and level of LH, FSH, testosterone beside the antioxidant enzyme activities (SOD, CAT, and MDA) (P < 0.001). Supplementation of FA in association with MDMA partially reversed these parameters and made them close to the control group. Conclusion: The results suggested that FA could reduce the adverse effect of MDMA on reproductive ability in adult male rats. [ABSTRACT FROM AUTHOR]

Background: Pentavalent antimonials such as meglumine antimoniate (MA, Glucantime), are the first-line treatment against leishmaniasis, but at present, they have basically lost their efficacy. This study was aimed to explore epigallocatechin 3-O-gallate (EGCG), alone or in combination with MA against Leishmania tropica stages. Methods: All experiments were carried out in triplicate using colorimetric assay, macrophage model, flow cytometry and quantitative real-time PCR. This experimental study was carried out in 2017 in Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran. Results: Promastigotes and amastigotes were more susceptible to EGCG than MA alone, but the effect was more profound when used in combination. EGCG exhibited high antioxidant level with a remarkable potential to induce apoptosis. Furthermore, the results showed that the level of gene expression pertaining to Th-1 was significantly up-regulated (P<0.001). Conclusion: EGCG demonstrated a potent anti-leishmanial effect alone and more enhanced lethal activity in combination. The principal mode of action entails the stimulation of a synergistic response and up-regulation of the immunomodulatory role towards Th-1 response against L. tropica. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported the antifertility activities of sulfonamides. This study was designed to evaluate the effects of co-trimoxazole and its co-administration with folic acid on ovarian tissue in female rats. Methods: A total of 54 rats were randomly divided into 9 groups (n=6). Group I served as the control and group II (vehicle) received saline. Other groups, III to IX, received co-trimoxazole (30, 60, and 120 mg/kg; i.p.), folic acid (1 mg/kg; i.p.) or their combination for 14 days, respectively. The oocytes were obtained from each group at the end of the 14th days and scored for maturational status as germinal vesicle (GV), metaphase I (MI), or metaphase II (MII). The number of primordial follicle (PrF), primary follicle (PF), and secondary follicle in formalin-fixed ovaries were counted under light microscopy. The data were analyzed by one-way ANOVA followed by post-hoc Dunnet test using SPSS statistical software (version 17.0). Results were considered statistically significant at P<0.05. Results: Co-trimoxazole (60 and 120 mg/kg) treatment for 14 days caused a significant decrease in the number of GV (P=0.02, P<0.001), MI and MII (P=0.03, P<0.001), a significant increase in structural abnormalities, including PrF, PF and secondary follicle (P<0.001) as well as congestion, inflammation and necrosis of ovarian tissue compared to the vehicle group. Folic acid co-administration with co-trimoxazole reversed partially all these parameters compared to the co-trimoxazole group (P<0.001). Conclusion: The data showed the adverse effects of co-trimoxazole on the ovarian maturational status and tissue structure which was reversed partially by folic acid co-administration in rats. [ABSTRACT FROM AUTHOR]

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 coadministration 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 14th and 28thdays. Sperm numbers, motility, and viability were evaluated on a hemocytometer. Hematoxylin and Eosin stained testes were done for evaluation ofthe 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 coadministration in rats. The underlying mechanism (s) needs further investigations. [ABSTRACT FROM AUTHOR]

Background: Methamphetamine (MAMP) as a recreational drug has devastating effects on the central nervous system (CNS). Several studies have shown that MAMP has inhibitory effects on oogenesis and spermatogenesis, and causes impaired fertility. This study designed to investigate the effect of mAM Padministration on histological changes and spermatogenesis indices in the testis of adult male rats. Methods: In this experimental study, 50 male Wistar rats were randomly divided into control (received no treatment, n = 10), vehicle (received saline for 7 and 14 days, n = 20), and experimental group [received MAMP, 5 ml/kg, intraperitoneal (IP) for 7 and 14 days, n = 20]. Testicular tissue samples were stained by hematoxylin and eosin (H&E) technique. For histological study, we counted the number of spermatogonia, spermatocytes and Leydig cells. Spermatogenesis indices which include: tubular differentiation index (TDI), spermiogenesis index (SI), repopulation index (RI) and the mean seminiferous tubules diameter (MSTD) were studied. Data were analyzed by one-way ANOVA, using SPSS software. P < 0.05 was considered statistically significant. Findings: This study showed that MAMP caused a significant decrease in number of seminiferous tubules cells and spermatogenesis in treated group compared with the control group. Moreover, results showed a significant decrease in spermatogenesis indices including TDI, SI, RI, and MSTD in 14th day, compared to control group (P < 0.001). Conclusion: The data showed the adverse effects of MAMP administration (for 7 and 14 days) on testes structure and spermatogenesis indices in rat testis tissue. The underlying mechanism(s) needs further investigation. [ABSTRACT FROM AUTHOR]