In Vitro | In vitro activity: Melatonin interacts with the highly toxic hydroxyl radical with a rate constant equivalent to that of other highly efficient hydroxyl radical scavengers. Melatonin reportedly neutralizes hydrogen peroxide, singlet oxygen, peroxynitrite anion, nitric oxide and hypochlorous acid. Melatonin is believed to scavenge the highly toxic hydroxyl radical, the peroxynitrite anion, and possibly the peroxyl radical. Melatonin reportedly scavenges the superoxide anion radical and it quenches singlet oxygen. Melatonin stimulates mRNA levels for superoxide dismutase and the activities of glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase (all of which are antioxidative enzymes), thereby increasing its antioxidative capacity. Melatonin in cell-free systems has been shown to directly scavenge H2O2, singlet oxygen (1O2) and nitric oxide (NO*), with little or no ability to scavenge the superoxide anion radical (O2*-) in vitro. Melatonin also directly detoxifies the peroxynitrite anion (ONOO-) and/or peroxynitrous acid (ONOOH), or the activated form of this molecule, ONOOH*. Melatonin acts as a direct free radical scavenger with the ability to detoxify both reactive oxygen and reactive nitrogen species. Melatonin inhibits cAMP accumulation in most of the cells examined, but the indole effects on other messengers have been often observed only in one type of the cells or tissue, until now. Melatonin also regulates the transcription factors, namely, phosphorylation of cAMP-responsive element binding protein and expression of c-Fos. |
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In Vivo | Melatonin increases the levels of activated PTEN, RSK-1, mTOR and AMPKα
kinases, mildly inhibits ERK-1/2 phosphorylation and Bad
phosphorylation, significantly inhibits phosphorylations of S6 Ribosomal
Protein, 4E-BP1, GSK-3α and GSK-3β, and slightly increases PRAS40
phosphorylation in animals. Melatonin ameliorates the neurotoxiciy and astrocyte activation induced by Aβ1-42 in the cerebral cortex. Melatonin also blocks the reduction in Reelin and Dab1 expression induced by Aβ1-42. Melatonin treatment and lack of NLRP3-/- share similar inhibition of NF-κB and NLRP3 signaling pathway in mice. Melatonin treatment and lack of NLRP3-/- share some patterns of clock genes expression, and improve cardiomyocytes morphology in mice. |
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Formulation & Dosage | A total of two sets of adult male C57BL/6j mice weighing 21-26 g are
randomly assigned to one of four groups and treated with intraperitoneal
(i.p.) delivery of (i) vehicle (50 μL isotonic saline/5% ethanol), (ii)
melatonin (4 mg/kg, dissolved in 0.9% isotonic saline/5% ethanol),
(iii) Wortmannin, and (iv) melatonin/Wortmannin immediately after
reperfusion. In the first set, mice are exposed to 30 min of focal
cerebral ischemia (FCI) and 72 h reperfusion for the evaluation of
disseminate ischemic injury in the striatum, and signaling pathway
analysis (n=7 per group). The second group of mice is exposed to 90 min
of FCI and 24 h reperfusion for the analysis of infarct development,
brain swelling and IgG extravasation (n=7 per group). |
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