Malaria : therapeutic implications of melatonin

• Autores: Srinivasan, Venkataramanujan; Spence, David Warren; Moscovitch, Adam; Pandi Perumal, Seithikurippu R.; Trakht, Ilya; Brown, Gregory M.; Cardinali, Daniel Pedro
• Año de publicación: 2010
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Journal of Pineal Research. 2010, 48 (1)
• Materia: MALARIA; RECEPTORES DE MELATONINA; APOPTOSIS; ESTRES OXIDATIVO; APLICACIONES TERAPEUTICAS
• Institución: Pontificia Universidad Católica Argentina

Fil: Srinivasan, Venkataramanujan. Sri Sathya Sai Medical Educational and Research Foundation; India
Fil: Spence, David Warren. Instituto Canadiense del Sueño; Canadá
Fil: Moscovitch, Adam. Instituto Canadiense del Sueño; Canadá
Fil: Pandi Perumal, Seithikurippu R. Somnogen Inc; Estados Unidos
Fil: Trakht, Ilya. Universidad Columbia. Colegio de Médicos y Cirujanos. Departamento de Medicina. División de Farmacología Clínica y Terapéutica Experimental; Estados Unidos
Fil: Brown, Gregory M. Universidad de Toronto. Departamento de Psiquiatría; Canadá
Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina
Abstract: Malaria, which infects more than 300 million people annually, is a serious disease. Epidemiological surveys indicate that of those who are affected, malaria will claim the lives of more than one million individuals, mostly children. There is evidence that the synchronous maturation of Plasmodium falciparum, the parasite that causes a severe form of malaria in humans and P. chabaudi, responsible for rodent malaria, could be linked to circadian changes in melatonin concentration. In vitro melatonin stimulates the growth and development of P. falciparum through the activation of specific melatonin receptors coupled to phospholipase-C activation and the concomitant increase of intracellular Ca2+. The Ca2+ signaling pathway is important to stimulate parasite transition from the trophozoite to the schizont stage, the final stage of intraerythrocytic cycle, thus promoting the rise of parasitemia. Either pinealectomy or the administration of the melatonin receptor blocking agent luzindole desynchronizes the parasitic cell cycle. Therefore the use of melatonin antagonists could be a novel therapeutic approach for controlling the disease. On the other hand, the complexity of melatonin’s action in malaria is underscored by the demonstration that treatment with high doses of melatonin is actually beneficial for inhibiting apoptosis and liver damage resulting from the oxidative stress in malaria. The possibility that the coordinated administration of melatonin antagonists (to impair the melatonin signal that synchronizes P. falciparum) and of melatonin in doses high enough to decrease oxidative damage could be a novel approach in malaria treatment is discussed.