Department of Pathogenic Biology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China.
Sichuan-Chongqing jointly-established Research Platform of Zoonosis, Chengdu, China.
Parasit Vectors. 2024 Jul 6;17(1):288. doi: 10.1186/s13071-024-06370-x.
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.
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.
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.
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.
目前，由于存在许多不良反应，内脏利什曼病（VL）的治疗方案受到限制。烟酰胺是一种易于获得且具有成本效益的维生素，其安全性已得到广泛认可。多项研究已经证明了烟酰胺在体外的抗利什曼原虫作用。然而，烟酰胺在体内利什曼原虫感染中的潜在作用仍不清楚。
在这项研究中，我们评估了烟酰胺作为一种治疗利什曼原虫感染的实验性小鼠模型中内脏利什曼病的疗效，并探讨了其潜在的分子机制。通过细胞因子分析、脾淋巴细胞亚群检查、肝 RNA-seq 分析和途径验证来探索潜在的分子机制。
与感染组相比，烟酰胺治疗组肝脾肿大和肝病理损伤得到明显改善。NAM 组肝、脾寄生虫减少率分别为 79.7%和 86.7%。烟酰胺治疗显著降低了感染小鼠过度免疫反应的激活，从而减轻了肝脾肿大和损伤。此外，烟酰胺治疗通过上调关键酶来增强脂肪酸β-氧化，从而维持脂质稳态。
我们的研究结果为烟酰胺在 BALB/c 小鼠利什曼原虫感染治疗中的安全性和疗效提供了初步证据，表明其作为一种有效的内脏利什曼病药物的潜力。
