Efeito neuroprotetor da melatonina e N-acetilserotonina na epileptogênese e no controle de crises em animais submetidos ao modelo da pilocarpina / Neuroprotector effect of melatonin and N-acetilserotonin in the epileptogenesis and in the control of seizures in animals submitted to the pilocarpine model

PURPOSE: The aim of this research was to study the effects of treatment with melatonin and N-acetilserotonin in the development of pilocarpina model of epilepsy in adult male rats. METHODS: Part I - The animals were divided in 4 groups: SALINE - animals that received only saline; SE - animals submitted to status epilepticus (SE); NAS + SE - animals that received pre-treatment with N-acetylserotonin and were submitted to SE and MEL + SE - animals that received pre-treatment with melatonin and were submitted to SE. Part II - The animals were divided in 6 groups: SALINE - animals that received only saline; SE - animals submitted to status epilepticus (SE); PX + SE - animals submitted to pinealectomy and to SE 7 days later; SH + SE - animals submitted to sham-surgery and to SE 7 days later; SE + NAS - animals submitted to SE and treated with N-acetylserotonin (2,5 mg/kg), 30 min, 1 h, 2 h, 4 h, 6 h, 12 h, 24 h, 36 h and 48 h after the SE and SE + MEL - animals submitted to SE and treated with melatonin (2,5 mg/kg), 30 min, 1 h, 2 h, 4 h, 6 h, 12 h, 24 h, 36 h and 48 h after the SE. Following the treatment the animals were continuously video-recorded for 60 days. The behavioral parameters were observed: latency for the SE in minutes, latency for the first spontaneous seizures (ie, duration of the silent period), number of spontaneous seizures during the chronic period and mortality. Five animals per group were perfused for neo-Timm assay. RESULTS: Part I - The animals treated with melatonin and N-acetylserotonin presented an increased of latency for the status epilepticus and decreased number of spontaneous seizures during the chronic period when compared to SE group. The mortality was reduced 100 percent in animals treated with melatonin and theses animals presented a minor mossy fibers sprouting. Part II - The latency for the first spontaneous seizures and mortality were similar in all groups. The animals treated with melatonin presented...

Neurobiología y farmacología clínica de la melatonina / Neurobiology and pharmacology of melatonin

La melatonina es una hormona sintetizada y liberada por la glándula pineal. La secreción comienza a aumentar alrededor de las 21.00-23.00 horas, observándose los niveles plasmáticos máximos entre las 2.00 y las 4.00 de la madrugada. Los fármacos bloqueadores de los adrenoceptores beta, los antiinflamatorio no esteroideos y los derivados benzodiacepínicos suprimen la liberación de melatonina. En cambio la zopiclona y el zopiclona y el zolpidem no interfieren en la liberación de la hormona. La melatonina es efectiva en los trastornos del sueño vinculados a una alteración del ritmo circadiano, incluyendo el jet lag, el cambio frecuente en el turno de trabajo y el trastorno de retardo de fase. También se ha mostrado eficaz en los trastornos del sueño de personas ciegas, donde la liberación de melatonina sigue un curso libre. Estudios recientes tienden a indicar que la melatonina es también efectiva en pacientes de la tercera edad con insomnio primario crónico acompañado de un descenso de los niveles endógenos de la hormona

velopment and characterization of a potential sustained release melatonin formulation: a possible modulatory influence of melatonin on glutathione s-transferases enzymes in rats

In this study, melatonin treatment in rats produced a significant elevation in hepatic cytosolic activity levels of GSTs and GSH-Px as well as glutathione [GSH] content with a reduction in lipid peroxide compared with the corresponding controls. In this study, a new preparation of melatonin "melatonin resinate-loaded microcapsules" was used. It prolonged and sustained the effect of melatonin up to 6 hours instead of 24 minutes [the half life in pure melatonin]. These new preparations produced a significant marked effects of melatonin on induction of GSTs and GSH-Px enzymes systems. It was concluded that melatonin particularly melatonin resinates loaded microcapsules induced the GSTs and GSH-Px enzyme systems in liver and this effect was potent than phenobarbitone. It was also suggested that melatonin exerts its antioxidants protective effects by stimulating the activities of detoxifying enzymes and may be through its direct antioxidant effects