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Study of the in vitro and in vivo antileishmanial activities of nimodipine in susceptible BALB/c mice
Reza Azadi1, Ghazal Alipour-Talesh2, Mohammad Javad Yazdanpanah1, Seyedeh Hoda Alavizadeh3, Masoud Maleki1, Mahnaz Banihashemi4, Mahmoud Reza Jaafari5
1 Research Center for Skin Diseases and Cutaneous Leishmaniasis; Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2 School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
3 Nanotechnology Research Center; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
4 Research Center for Skin Diseases and Cutaneous Leishmaniasis, Mashhad University of Medical Sciences, Mashhad, Iran
5 Nanotechnology Research Center; Department of Pharmaceutical Nanotechnology, School of Pharmacy; Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Correspondence Address:
Mahmoud Reza Jaafari,
Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad
Iran
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/0972-9062.308805
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Background & objectives: Pentavalent antimonials are the standard treatment for cutaneous leishmaniasis (CL), however, treatment failures are frequent. Nimodipine, a calcium channel blocker is known to show promising antiprotozoal effects. Here, we investigated the antileishmanial effect of Nimodipine in both in vitro and in vivo BALB/c mice model of CL. We also compared the in vivo effect with amphotericin B and meglumine antimoniate in the experimental CL mice model.
Methods: Colorimetric alamar blue assay and J774 A.1 mouse macrophage cells were used to determine the effect of nimodipine on promastigotes and amastigotes viability, respectively. Then, the in vivo activity of nimodipine was compared to that of conventional therapies in both the early and established courses of Leishmania major infection in susceptible non-healing BALB/c mice.
Results: Nimodipine was highly active against promastigotes and amastigotes of L. major with IC50 values of 49.40 and 15.03 μM, respectively. In the early model, the combination therapy with meglumine antimoniate and nimodipine showed no parasites in the spleen or footpad of animals. The footpad thickness was significantly lower in mice treated with either nimodipine (1 mg/kg or 2.5 mg/kg) or amphotericin B compared to the control group in the established lesions model. However, no complete remission was observed in the footpad lesion of any of the treatment groups (nimodipine, amphotericin B, meglumine antimoniate, and combination therapy).
Interpretation & conclusion: The effect of nimodipine was comparable to that of amphotericin B and meglumine antimoniate in early and established CL lesion models. Since nimodipine is more cost-effective than conventional therapies, our results merit further investigation in other animal models and voluntary human subjects. |
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