Department of Microbiology, Faculty of Medicine, University of Granada, Granada, Spain; Department of Zoonotic diseases, Faculty of Veterinary Medicine, Sohag University, Sohag, Egypt.
Department of Pharmacology and Neurosciences Institute (CIBM), Faculty of Medicine, University of Granada, Granada, Spain.
Chem Biol Interact. 2014 Sep 5;220:84-93. doi: 10.1016/j.cbi.2014.06.016. Epub 2014 Jun 25.
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.
内脏利什曼病是一种潜在致命的疾病，仍然是一个重大的国际健康问题。目前仅有少数几种有效的抗利什曼原虫药物可用于化疗，其中许多药物价格昂贵，副作用严重，或者由于耐药性的发展而显著降低了疗效。因此，确实需要开发一种新型的有效且毒性较低的抗利什曼原虫药物。褪黑素是一种在动物、植物和微生物中发现的神经激素，它可以参与各种生物和生理功能。一些体外或体内研究报告称，褪黑素通过多种机制对许多寄生虫具有抑制作用，包括调节寄生虫细胞内的钙浓度和/或任何其他建议的机制。重要的是，许多现有的抗利什曼原虫药物已被报道通过破坏寄生虫体内的钙稳态发挥作用。本研究的目的是测试外源性褪黑素对利什曼原虫前鞭毛体的体外疗效。有趣的是，褪黑素不仅显著抑制了测试培养物中前鞭毛体的活力，而且还改变了寄生虫线粒体的钙稳态，表现为早期线粒体通透性转换孔的开放，以及一些线粒体参数的变化对寄生虫的生存至关重要。这些开创性的发现表明，褪黑素可能是开发新型有效抗利什曼原虫药物的候选药物，无论是单独使用还是与其他药物联合使用。
