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The Fraction of the Snake Venom, its Leishmanicidal Effect, and the Stimulation of an Anti-Leishmania Response in Infected Macrophages

[ Vol. 21 , Issue. 6 ]

Author(s):

Saeideh Nikpour, Fatemeh Tabatabaie*, Iraj Sharifi, Mahshid Mostafavi, Razieh T. Oliaee, Fatemeh Sharifi, Zahra Babaei, Elham Jafari, Ehsan Salarkia and Delavar Shahbazzadeh   Pages 1144 - 1153 ( 10 )

Abstract:


Background and Aims: Due to the lack of an effective vaccine and complexity of the control measures against vectors and reservoir hosts, the control of leishmaniasis depends primarily on chemotherapy. This study was aimed to assess the snake venom, Naja naja oxiana fraction 11(NNOVF11) on Leishmania infantum and its broad mode of action.

Methods: A wide range of in vitro advanced assays including high-performance liquid chromatography (HPLC), MTT (3-[4, 5-Dimethylthiazol-2-yl]-2, 5diphenyltetrazolium bromide; Thiazolyl blue), macrophage assays, quantitative real-time polymerase chain reaction (qPCR), flow cytometry and enzyme- linked immunosorbent assay (ELISA) on L. infantum promastigote and amastigote stages were used. IC50 values of L. infantum stages, CC50 value, and apoptosis were also analyzed.

Results: The NNOV-F11 demonstrated strong antileishmanial activity against L. infantum stages in a dose-dependent manner compared to the untreated control group. Interleukin (IL)-12, TNF-α, and iNOS genes expression as the indicators of T helper(h)1 response significantly increased; in contrast, the expression level of IL-10, as the representative of Th2 response significantly decreased (p < 0.001). Reactive oxygen species (ROS) detection showed a significant increase (p < 0.001) after treatment with different concentrations of NNOV-F11, unlike arginase (ARG) activity, which displayed a significant reduction (p < 0.001).

Conclusion: NNOV-F11 possessed a potent inhibitory effect on L. infantum stages with the multifunctional and broad mode of actions, which promoted the immunomodulatory role, induced ROS production, stimulated apoptotic–like mechanisms, and inhibited L-ARG activity, which collectively led to the parasite death. Further studies are crucial to assess the effect of the NNOV-F11 on animal models or clinical settings.

Keywords:

Snake venom, Leishmania infantum, ELISA, T helper, antileishmanial activity, Naja naja oxiana.

Affiliation:

Department of Parasitology and Mycology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Department of Parasitology and Mycology, Faculty of Medicine, Iran University of Medical Sciences, Tehran,, Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Pathology and Stem Cell Research Center, Kerman University of Medical Science, Kerman, Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Laboratory of Venom and Biotherapeutics Molecules, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran



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