Abstract
Purpose
The aim of this study was to explore the activity of Naja naja oxiana venom on Leishmania tropica and its modes of action.
Methods
Different fractions of Naja naja oxiana venom (NNOV) were prepared and characterized by high-performance liquid chromatography. The superior component, fraction k (FK) was selected. The activity of the fraction was assessed using advanced assays.
Results
Interleukin (IL)-12, TNF-α and iNOS gene expression as the indicators of Th1 significantly increased. In contrast, the level of IL-10, as the marker of T helper 2 substantially decreased (p < 0.001). Reactive oxygen species (ROS) detection showed a significant increase (p < 0.001) after treatment with different concentrations of NNOV-FK, unlike arginase (L-ARG) activity which showed a significant reduction (p < 0.001). The NNOV-FK showed significant lethal activity on the L. tropica stages.
Conclusion
The findings demonstrated that NNOV-FK represented a strong leishmanicidal activity on L. tropica stages. The major modes of NNOV-FK action are multidimensional, which perceives the induction of a synergistic response and upregulation of the immune-modulatory role towards Th1 response against L. tropica stages as well as apoptotic and anti-metabolic action as a model drug to generate ROS, block the polyamine synthesis and lead to parasite death.
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Acknowledgements
The authors would like to thank Iran University of Medical Sciences and the Kerman Leishmaniasis Research Center (Kerman University of Medical Sciences) for their support.
Funding
This work was supported by Iran University of Medical Sciences [Code: 98-1-4-14314] and the Kerman Leishmaniasis Research Center and Vice-Chancellor for Research (Contract numbers. 97000079 and 98-1-4-14314).
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This study was approved by the Ethics Committees of Iran University of Medical Sciences in accordance with guidelines and the Kerman Leishmaniasis Research Center and Vice-Chancellor for Research. The designated approval codes are: IR.IUMS.FMD.REC.1398.040 and IR. KMU. REC 1397.215.
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Sharifi, I., Tabatabaie, F., Nikpour, S. et al. The Effect of Naja naja oxiana Snake Venom Against Leishmania tropica Confirmed by Advanced Assays. Acta Parasit. (2020). https://doi.org/10.1007/s11686-020-00301-3
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Keywords
- Leishmania tropica
- Snake venom fractions
- Leishmanicidal effect
- Mechanism of action