title: Activity of melatonin against Leishmania infantum promastigotes by mitochondrial dependent pathway.
abstract: 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.
authors: Department of Microbiology, Faculty of Medicine, University of Granada, Granada, Spain; Department of Zoonotic diseases, Faculty of Veterinary Medicine, Sohag University, Sohag, Egypt.
authors: Ehab Kotb
authors: EK
authors: Elmahallawy
authors: Department of Pharmacology and Neurosciences Institute (CIBM), Faculty of Medicine, University of Granada, Granada, Spain.
authors: Aroa
authors: A
authors: Jiménez-Aranda
authors: Service of Microbiology and Parasitology, University Hospital Virgen de las Nieves, Granada, Spain.
authors: Antonio Sampedro
authors: AS
authors: Martínez
authors: Service of Microbiology and Parasitology, University Hospital Virgen de las Nieves, Granada, Spain.
authors: Javier
authors: J
authors: Rodriguez-Granger
authors: Department of Nutrition and Food Science, School of Pharmacy, University of Granada, Granada, Spain.
authors: Miguel
authors: M
authors: Navarro-Alarcón
authors: Department of Microbiology, Faculty of Medicine, University of Granada, Granada, Spain.
authors: José
authors: J
authors: Gutiérrez-Fernández
authors: Department of Pharmacology and Neurosciences Institute (CIBM), Faculty of Medicine, University of Granada, Granada, Spain. Electronic address: aagil@ugr.es.
authors: Ahmad
authors: A
authors: Agil
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D018314:Leishmania infantum / Q000187:drug effects; D008550:Melatonin / Q000494:pharmacology*; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D009573:Nitrites / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D009573:Nitrites; D013482:Superoxide Dismutase; D008550:Melatonin
keywords: Leishmania infantum; Melatonin; Mitochondria; Promastigotes