Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran; Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.
Int Immunopharmacol. 2020 Sep;86:106704. doi: 10.1016/j.intimp.2020.106704. Epub 2020 Jun 23.
Leishmaniasis represents a major health concern worldwide which has no effective treatment modality. Nicotinamide (NAm) has been used for a wide range of applications from anticancer to antimicrobial usage. This study aimed to assess the effect of NAm combination on Leishmania tropica Inhibition, as well as on cytokines gene expression and arginase (ARG) activity in L. tropica-infected macrophages in an in vitro model. The leishmanicidal effects of NAm and Glucantime (meglumine antimoniate, MA) alone and in combination (NAm/MA) were evaluated using a colorimetric assay and macrophage model. Additionally, immunomodulatory effects and enzymatic activity were assessed by analyzing Th1 and Th2 cytokines gene expression and ARG level, respectively, in infected macrophages treated with NAm and MA, alone and in combination. Findings indicated that the NAm/MA combination demonstrated greater inhibitory effects on L. tropica promastigotes and amastigotes compared with each drug individually. Docking results proved the affinity of NAm to IFN-γ, which can affirm the increased levels of IFN-γ, IL-12p40 and TNF-α as well as reductions in IL-10 secretion with a dose-response effect, especially in the combination group. The NAm/MA combination also showed a significant reduction in the level of ARG activity at all concentrations used compared to each drug individually. These findings indicate higher effectiveness of NAm plus MA in reducing parasite growth, promoting immune response and inhibiting ARG level. This combination should be considered as a potential therapeutic regimen for treatment of volunteer patients with anthroponotic cutaneous leishmaniasis (ACL) in future control programs.
利什曼病是全球范围内的一个主要健康关注点，目前尚无有效的治疗方法。烟酰胺 (NAm) 已被广泛应用于从抗癌到抗菌的各种用途。本研究旨在评估 NAm 联合治疗对利什曼原虫热带株的抑制作用，以及对体外模型中利什曼原虫感染的巨噬细胞细胞因子基因表达和精氨酸酶 (ARG) 活性的影响。通过比色法和巨噬细胞模型评估 NAm 和葡萄糖酸锑钠 (Glucantime, MA) 单独和联合应用的杀利什曼原虫效果。此外，通过分析感染巨噬细胞中 Th1 和 Th2 细胞因子基因表达和 ARG 水平，评估 NAm 和 MA 单独和联合应用的免疫调节作用和酶活性。研究结果表明，与每种药物单独应用相比，NAm/MA 联合应用对利什曼原虫前鞭毛体和无鞭毛体具有更强的抑制作用。对接结果证明了 NAm 与 IFN-γ 的亲和力，这可以证实 IFN-γ、IL-12p40 和 TNF-α 水平的增加以及 IL-10 分泌的减少具有剂量反应效应，尤其是在联合组中。与每种药物单独应用相比，NAm/MA 联合应用在所有使用浓度下均显著降低了 ARG 活性水平。这些发现表明，NAm 加 MA 联合应用在减少寄生虫生长、促进免疫反应和抑制 ARG 水平方面具有更高的有效性。在未来的控制计划中，这种联合应用应被视为治疗人类皮肤利什曼病（ACL）志愿者患者的一种潜在治疗方案。
