Iraj Sharifi1, Fatemeh Tabatabaie2, Saeideh Nikpour3, Mahshid Mostafavi1, Razieh Tavakoli Oliaee1, Fatemeh Sharifi4, Zahra Babaei1, Elham Jafari5, Ehsan Salarkia1, Delavar Shahbazzadeh6. 1. Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran. 2. Department of Parasitology and Mycology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. tabatabaie.f98@gmail.com. 3. Department of Parasitology and Mycology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. saeidehnikpour@yahoo.com. 4. Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran. 5. Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman, Iran. 6. Laboratory of Venom and Biotherapeutics Molecules, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
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.
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.
Authors: Jaime M Soto; Julia T Toledo; Patricia Gutierrez; Margarita Arboleda; Ruben S Nicholls; Julio R Padilla; Jonathan D Berman; Charles K English; Max Grogl Journal: Am J Trop Med Hyg Date: 2002-02 Impact factor: 2.345
Authors: Flávio José Dutra de Moura; Pushkin Pires Leal; Rogério de Souza Furtado; Maria Imaculada Muniz-Junqueira; Joel Paulo Russomano Veiga Journal: Toxicology Date: 2007-10-07 Impact factor: 4.221
Authors: Freddie Bailey; Karina Mondragon-Shem; Peter Hotez; José Antonio Ruiz-Postigo; Waleed Al-Salem; Álvaro Acosta-Serrano; David H Molyneux Journal: PLoS Negl Trop Dis Date: 2017-08-10
Authors: Mohammad Reza Aflatoonian; Iraj Sharifi; Behnaz Aflatoonian; Mehdi Bamorovat; Amireh Heshmatkhah; Zahra Babaei; Pooya Ghasemi Nejad Almani; Mohammad Ali Mohammadi; Ehsan Salarkia; Abbas Aghaei Afshar; Hamid Sharifi; Fatemeh Sharifi; Ahmad Khosravi; Mehrdad Khatami; Nasir Arefinia; Alireza Fekri; Saeideh Farajzadeh; Ali Khamesipour; Mehdi Mohebali; Mohammad Mehdi Gouya; Mohammad Reza Shirzadi; Rajender S Varma Journal: PLoS Negl Trop Dis Date: 2019-06-12