BACKGROUND Metformin (MET) is a hypoglycemic drug used for the treatment of diabetes, despite interference in host immunity against microorganisms. Cutaneous infection caused by pathogens such as Leishmania braziliensis (Lb), the agent responsible for cutaneous leishmaniasis (CL) in Brazil, represents an interesting model in which to evaluate the effects associated with MET. OBJECTIVE To evaluate the modulatory effect of MET in Lb infection. MATERIAL AND METHODS Experimental study of Lb infection and MET treatment in BALB/c mice and Raw 264.7 macrophages. FINDINGS MET treatment interfered with lesion kinetics, increased parasite load and reduced macrophage proliferation. Low concentrations of MET in Lb culture allow for the maintenance of stationary parasite growth phase. Lb-infected cells treated with MET exhibited increased parasite load. While both MET and Lb infection alone promoted the production of intracellular reactive oxygen species (ROS), reduced levels of ROS were seen in MET-treated Lb-infected macrophages. MAIN CONCLUSION Experimental treatment with MET interfered with the kinetics of cutaneous ulceration, increased Lb parasite load, altered ROS production and modulated cellular proliferation. Our experimental results indicate that MET interfere with the evolution of CL.

中文翻译：

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二甲双胍促进实验性巴西利什曼原虫感染的易感性


背景技术二甲双胍(MET)是一种用于治疗糖尿病的降血糖药物，尽管它会干扰宿主对微生物的免疫。由巴西利什曼原虫 (Lb)（巴西皮肤利什曼病 (CL) 的病原体）等病原体引起的皮肤感染代表了一个有趣的模型，可用于评估与 MET 相关的影响。目的评价MET对Lb感染的调节作用。材料和方法 BALB/c 小鼠和 Raw 264.7 巨噬细胞中 Lb 感染和 MET 治疗的实验研究。结果 MET 治疗会干扰病变动力学、增加寄生虫负荷并减少巨噬细胞增殖。 Lb 培养物中低浓度的 MET 可以维持寄生虫的静止生长期。用 MET 处理的 Lb 感染细胞表现出寄生虫负载增加。虽然 MET 和 Lb 感染单独促进细胞内活性氧 (ROS) 的产生，但在 MET 处理的 Lb 感染巨噬细胞中发现 ROS 水平降低。主要结论 MET 实验性治疗可干扰皮肤溃疡的动力学、增加 Lb 寄生虫负荷、改变 ROS 产生并调节细胞增殖。我们的实验结果表明 MET 干扰 CL 的进化。