Activity of melatonin against Leishmania infantum promastigotes by mitochondrial dependent pathway Elmahallawy, Ehab Kotb Jiménez-Aranda, Aroa Sampedro Martínez, Antonio Rodriguez-Granger, Javier Navarro-Alarcón, Miguel Gutiérrez Fernández, José Agil Abdalla, Mhmad Ahmad Melatonin Leishmania infantum Promastigotes Mitochondria E.K. Elmahallawy received an Erasmus Mundus scholarship. The study was also supported in part by CTS-109 group from the Junta de Andalucía (Spain) and by SAF2013-45752-R group from the Ministerio de Economía y Competitividad (Spain). Visceral leishmaniasis, a potentially fatal disease, remains a major international health problem. Only a limited number of effective antileishmanial agents are available for chemotherapy, and many of them are expensive with severe side effects or have a markedly reduced effectiveness due to the development of drug resistance. Hence, there is a genuine need to develop a novel effective and less toxic antileishmanial drug. Melatonin, a neurohormone found in animals, plants, and microbes, can participate in various biological and physiological functions. Several in vitro or in vivo studies have reported the inhibitory effect of melatonin against many parasites via various mechanisms, including modulation of intracellular concentrations of calcium in the parasite and/or any other suggested mechanism. Importantly, many of available antileishmanial drugs have been reported to exert their effects by disrupting calcium homeostasis in the parasite. The objective of the present study was to test the efficacy of exogenous melatonin against Leishmania infantum promastigotes in vitro. Interestingly, melatonin not only demonstrated a significant antileishmanial activity of against promastigote viability in tested cultures but was also accompanied by an alteration of the calcium homeostasis of parasite mitochondrion, represented by earlier mitochondrial permeability transition pore opening, and by changes in some mitochondrial parameters are critical to parasite survival. These pioneering findings suggest that melatonin may be a candidate for the development of novel effective antileishmanial agents either alone or in associations with other drugs. 2024-03-12T12:09:05Z 2024-03-12T12:09:05Z 2014-09-05 info:eu-repo/semantics/article Elmahallawy EK, Jiménez-Aranda A, Martínez AS, Rodriguez-Granger J, Navarro-Alarcón M, Gutiérrez-Fernández J, Agil A. Activity of melatonin against Leishmania infantum promastigotes by mitochondrial dependent pathway. Chem Biol Interact. 2014 Sep 5;220:84-93. https://doi.org/10.1016/j.cbi.2014.06.016 https://hdl.handle.net/10481/89944 10.1016/j.cbi.2014.06.016 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional Chemico-Biological Interactions