Journal of pineal research
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We tested the hypothesis that melatonin regulates formation of 6-hydroxydopamine (6-OHDA) in the brain and thereby protects animals from dopaminergic neurotoxicity and the development of parkinsonism in animals. Employing a ferrous-ascorbate-dopamine (FAD) hydroxyl radical ((*)OH) generating system, in the present study we demonstrate a dose-dependent attenuation of 6-OHDA generation by melatonin in vitro. ⋯ Melatonin treatment significantly attenuated both the L-DOPA and MPTP-induced increases in the levels of striatal 6-OHDA, and protected against striatal DA depletion caused by the neurotoxin. These observations suggest a novel mode of melatonin-induced dopaminergic neuroprotection in two models of Parkinson's disease, and suggest the possible therapeutic use of this well-known antioxidant indoleamine neurohormone in parkinsonism.
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Sleep disorders cause cognitive dysfunction in which impaired neuronal plasticity in the hippocampus may underline the molecular mechanisms of this deficiency. As sirtuin 1 (SIRT1) plays an important role in maintaining metabolic homeostasis and neuronal plasticity, this study is aimed to determine whether melatonin exerts beneficial effects on preserving SIRT1 activation following total sleep deprivation (TSD). TSD was performed by disc on water method for five consecutive days. ⋯ However, in rats receiving different doses of melatonin, both COX and SIRT1 expressions were successfully preserved. Considerably better performance on behavioral testing further strengthened the beneficial effects of melatonin. These findings suggest that melatonin may serve as a novel therapeutic strategy directed for preventing the memory deficits resulting from TSD, possibly by effectively preserving the metabolic function and neuronal plasticity engaged in maintaining cognitive activity.
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Oxidative stress has detrimental effects in several models of neurodegenerative diseases, including subarachnoid hemorrhage (SAH). This study investigated the putative neuroprotective effect of melatonin, a powerful antioxidant, in a rat model of SAH. Male Wistar albino rats were divided as control, vehicle-treated SAH, and melatonin-treated (10 mg/kg, i.p.) SAH groups. ⋯ The neurological examination scores were increased in SAH groups on the second day of SAH induction and SAH caused a significant decrease in brain GSH content and Na+-K+-ATPase activity, which was accompanied with significant increases in CL, MDA levels, and MPO activity. On the other hand, melatonin treatment reversed all these biochemical indices as well as SAH-induced histopathological alterations, while increased brain water content and impaired BBB were also reversed by melatonin treatment. This study suggests that melatonin, which can easily cross BBB, alleviates SAH-induced oxidative stress and exerts neuroprotection by preserving BBB permeability and by reducing brain edema.
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Acute renal dysfunction is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). This study was designed to evaluate the potential protective effect of melatonin on CPB-induced renal damage in a rat model. Forty male Sprague-Dawley rats were randomly divided into four groups: sham, control (CPB + placebo), low dose of melatonin (CPB + 10 mg/kg melatonin) and high dose of melatonin (CPB + 20 mg/kg melatonin). ⋯ These changes were markedly reversed in both low dose of melatonin and high dose of melatonin groups. Furthermore, HO-1 gene transcript and protein were significantly upregulated in the kidney tissues after melatonin treatment compared with the placebo treatment. Our findings show that melatonin was effective in preventing CPB-induced renal damage probably through its antioxidant function and upregulation of HO-1.
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Newborns, and especially those delivered preterm, are probably more prone to oxidative stress than individuals later in life. Also during pregnancy, increased oxygen demand augments the rate of production of reactive oxygen species (ROS) and women, even with normal pregnancies, experience elevated oxidative stress and lipid peroxidation compared with nonpregnant women. Also, there appears to be an increase in ROS generation in the placenta of pre-eclamptic women. ⋯ Significant complications with long-term melatonin therapy in children and adults also have not been reported. None of the animal studies of maternal melatonin treatment or in postnatal life have shown any treatment-related side effects. The authors conclude that treatment with melatonin might result in a wide range of health benefits, improved quality of life and reduced healthcare costs and may help reduce complications in the neonatal period.