PDF(Pubmed)
Abstract：
BACKGROUND: Currently, treatment regimens for visceral leishmaniasis (VL) are limited because of the presence of numerous adverse effects. Nicotinamide, a readily available and cost-effective vitamin, has been widely acknowledged for its safety profile. Several studies have demonstrated the anti-leishmanial effects of nicotinamide in vitro. However, the potential role of nicotinamide in Leishmania infection in vivo remains elusive.
METHODS: In this study, we assessed the efficacy of nicotinamide as a therapeutic intervention for VL caused by Leishmania infantum in an experimental mouse model and investigated its underlying molecular mechanisms. The potential molecular mechanism was explored through cytokine analysis, examination of spleen lymphocyte subsets, liver RNA-seq analysis, and pathway validation.
RESULTS: Compared to the infection group, the group treated with nicotinamide demonstrated significant amelioration of hepatosplenomegaly and recovery from liver pathological damage. The NAM group exhibited parasite reduction rates of 79.7% in the liver and 86.7% in the spleen, respectively. Nicotinamide treatment significantly reduced the activation of excessive immune response in infected mice, thereby mitigating hepatosplenomegaly and injury. Furthermore, nicotinamide treatment enhanced fatty acid β-oxidation by upregulating key enzymes to maintain lipid homeostasis.
CONCLUSIONS: Our findings provide initial evidence supporting the safety and therapeutic efficacy of nicotinamide in the treatment of Leishmania infection in BALB/c mice, suggesting its potential as a viable drug for VL.
METHODS: In this study, we assessed the efficacy of nicotinamide as a therapeutic intervention for VL caused by Leishmania infantum in an experimental mouse model and investigated its underlying molecular mechanisms. The potential molecular mechanism was explored through cytokine analysis, examination of spleen lymphocyte subsets, liver RNA-seq analysis, and pathway validation.
RESULTS: Compared to the infection group, the group treated with nicotinamide demonstrated significant amelioration of hepatosplenomegaly and recovery from liver pathological damage. The NAM group exhibited parasite reduction rates of 79.7% in the liver and 86.7% in the spleen, respectively. Nicotinamide treatment significantly reduced the activation of excessive immune response in infected mice, thereby mitigating hepatosplenomegaly and injury. Furthermore, nicotinamide treatment enhanced fatty acid β-oxidation by upregulating key enzymes to maintain lipid homeostasis.
CONCLUSIONS: Our findings provide initial evidence supporting the safety and therapeutic efficacy of nicotinamide in the treatment of Leishmania infection in BALB/c mice, suggesting its potential as a viable drug for VL.
摘要：
背景：目前，内脏利什曼病（VL）的治疗方案由于存在许多不良反应而受到限制。烟酰胺,一种容易获得且具有成本效益的维生素，其安全性已得到广泛认可。一些研究已经证明了烟酰胺在体外的抗利什曼虫作用。然而,烟酰胺在体内利什曼原虫感染中的潜在作用仍然难以捉摸。
方法：在本研究中，我们在实验性小鼠模型中评估了烟酰胺作为婴儿利什曼原虫引起的VL治疗干预的疗效,并研究了其潜在的分子机制.通过细胞因子分析探索潜在的分子机制，检查脾淋巴细胞亚群，肝脏RNA-seq分析，和途径验证。
结果：与感染组相比，烟酰胺治疗组表现出肝脾肿大的显著改善和肝脏病理损伤的恢复。NAM组显示肝脏寄生虫减少率为79.7%，脾脏减少率为86.7%，分别。烟酰胺处理显著降低感染小鼠的过度免疫应答的激活,从而减轻肝脾肿大和损伤。此外，烟酰胺处理通过上调关键酶以维持脂质稳态来增强脂肪酸β-氧化。
结论：我们的研究结果提供了初步证据，支持烟酰胺治疗利什曼原虫感染的BALB/c小鼠的安全性和治疗效果。表明其作为VL的可行药物的潜力。
方法：在本研究中，我们在实验性小鼠模型中评估了烟酰胺作为婴儿利什曼原虫引起的VL治疗干预的疗效,并研究了其潜在的分子机制.通过细胞因子分析探索潜在的分子机制，检查脾淋巴细胞亚群，肝脏RNA-seq分析，和途径验证。
结果：与感染组相比，烟酰胺治疗组表现出肝脾肿大的显著改善和肝脏病理损伤的恢复。NAM组显示肝脏寄生虫减少率为79.7%，脾脏减少率为86.7%，分别。烟酰胺处理显著降低感染小鼠的过度免疫应答的激活,从而减轻肝脾肿大和损伤。此外，烟酰胺处理通过上调关键酶以维持脂质稳态来增强脂肪酸β-氧化。
结论：我们的研究结果提供了初步证据，支持烟酰胺治疗利什曼原虫感染的BALB/c小鼠的安全性和治疗效果。表明其作为VL的可行药物的潜力。
