Efficacy of amiodarone and voriconazole combination therapy in cutaneous leishmaniasis in the mice experimentally infected with Leishmania major

Abstract

IntroductionThe 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. Methods: 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. Results: 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. Conclusions: It seems a combination of amiodarone plus voriconazole can be a rational and promising therapeutic approach in the treatment of cutaneous leishmaniasis.