Department of Parasitology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
Department of Pathology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
J Infect Chemother. 2021 Jul;27(7):984-990. doi: 10.1016/j.jiac.2021.02.011. Epub 2021 Feb 23.
The aim of the present study was to evaluate in vitro and in vivo efficacy of combination therapy of amiodarone and voriconazole against Leishmania major and investigating immune and wound healing responses of cutaneous leishmaniasis to this combination therapy.
For in vitro study, replication of L. major promastigotes and intracellular amastigotes were investigated in the presence and absence of amiodarone and voriconazole. Isobologram construction and calculation of the Fractional Inhibitory Concentration (FIC) were performed. After the appearance of ulcers on the base of tails of BALB/c mice, treatment was initiated by a combination of amiodarone at 40 mg/kg plus voriconazole at 30 mg/kg orally and glucantime at 60 mg/kg intraperitoneally for 28 consecutive days.
According to the concave isobologram and fractional inhibitory concentration <1, combination of amiodarone plus voriconazole had synergistic effects against L. major promastigotes and intracellular amastigotes. There were less inflammatory cells, more fibroblasts and more collagen deposition in tissue sections in the mice treated with combined drugs compared to the vehicle and untreated mice. Increased glutathione peroxidase activity and decreased malondialdehyde, Interleukin-6, and Tumor necrosis factor-α levels were detected in the combination therapy group in comparison to the vehicle and untreated groups.
It seems a combination of amiodarone plus voriconazole can be a rational and promising therapeutic approach in the treatment of cutaneous leishmaniasis.
本研究旨在评估胺碘酮和伏立康唑联合治疗对利什曼原虫的体内外疗效，并研究其对皮肤利什曼病的免疫和伤口愈合反应。
为了进行体外研究，在存在和不存在胺碘酮和伏立康唑的情况下，研究了 L. major 前鞭毛体和细胞内无鞭毛体的复制。构建等辐射图并计算部分抑制浓度（FIC）。在 BALB/c 小鼠尾部出现溃疡后，开始联合治疗，口服胺碘酮 40mg/kg 加伏立康唑 30mg/kg，腹腔内注射葡萄糖胺 60mg/kg，连续 28 天。
根据凹面等辐射图和分数抑制浓度<1，胺碘酮加伏立康唑联合使用对 L. major 前鞭毛体和细胞内无鞭毛体具有协同作用。与载体和未治疗组相比，联合用药组的组织切片中炎症细胞较少，成纤维细胞较多，胶原沉积较多。与载体和未治疗组相比，联合治疗组的谷胱甘肽过氧化物酶活性增加，丙二醛、白细胞介素 6 和肿瘤坏死因子-α水平降低。
胺碘酮加伏立康唑联合治疗似乎是治疗皮肤利什曼病的一种合理且有前途的治疗方法。
