Journal of pineal research
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Melatonin had previously been shown to reduce up to four 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) cation radicals (ABTS*+) via a scavenger cascade ending with N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK). However, when melatonin is added to the reaction system in much lower quantities than ABTS*+, the number of radicals scavenged per melatonin molecule is considerably higher and can attain a value of ten. Under conditions allowing for such a stoichiometry, novel products have been detected which derive from AFMK (1). ⋯ When H2O2 is added to the ABTS*+ reaction mixture in quantities not already leading to substantial reduction of this radical, compound 3 is isolated as the major product, whereas 2a and 2b are virtually absent. The substances formed differ from all previously known oxidation products which derive from melatonin and are, among these, the first 3-indolinones. Moreover, the aliphatic side chain at C2 is reminiscent of other substances which have been synthesized in the search for melatonin receptor ligands.
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Mitochondrial nitric oxide synthase (mtNOS) produces nitric oxide (NO) to modulate mitochondrial respiration. Besides a constitutive mtNOS isoform it was recently suggested that mitochondria express an inducible isoform of the enzyme during sepsis. Thus, the mitochondrial respiratory inhibition and energy failure underlying skeletal muscle contractility failure observed in sepsis may reflect the high levels of NO produced by inducible mtNOS. ⋯ Mitochondria from iNOS(-/-) mice were unaffected by either sepsis or melatonin treatment. The data suggest that inducible mtNOS, which is coded by the same gene as that for iNOS, is responsible for mitochondrial dysfunction during sepsis. The results also suggest the use of melatonin for the protection against mtNOS-mediated mitochondrial failure.
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Review Meta Analysis
Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis.
Most observational studies show an association between melatonin and cancer in humans. We conducted a systematic review of randomized controlled trials (RCTs) of melatonin in solid tumor cancer patients and its effect on survival at 1 yr. With the aid of an information specialist, we searched 10 electronic databases from inception to October 2004. ⋯ No severe adverse events were reported. The substantial reduction in risk of death, low adverse events reported and low costs related to this intervention suggest great potential for melatonin in treating cancer. Confirming the efficacy and safety of melatonin in cancer treatment will require completion of blinded, independently conducted RCTs.
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Septic shock, the most severe problem of sepsis, is a lethal condition caused by the interaction of a pathogen-induced long chain of sequential intracellular events in immune cells, epithelium, endothelium, and the neuroendocrine system. The lethal effects of septic shock are associated with the production and release of numerous pro-inflammatory biochemical mediators including cytokines, nitric oxide and toxic oxygen and nitrogen radicals, together with development of massive apoptosis. As melatonin has remarkable properties as a cytokine modulator, antioxidant and anti-apoptotic agent, the present study was designed to evaluate the possible protective effect of melatonin against LPS-induced septic shock in Swiss mice. ⋯ Melatonin was able to partially counteract the increase in LPS-induced pro-inflammatory cytokine levels such as tumor necrosis factor-alpha, IL-12 and interferon-gamma at the local site of injection, while it increased the production of the anti-inflammatory cytokine IL-10 both locally and systemically. Furthermore, melatonin inhibited the LPS-induced nitrite/nitrate and lipid peroxidation levels in brain and liver and counteracted the sepsis-associated apoptotic process in spleen. In conclusion, we have demonstrated that melatonin improves the survival of mice with septic shock via its pleiotropic functions as an immunomodulator, antioxidant and anti-apoptotic mediator.
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Comparative Study
Long-term effects of melatonin or 17 beta-estradiol on improving spatial memory performance in cognitively impaired, ovariectomized adult rats.
Melatonin is an endogenously generated potent antioxidant. Our previous studies indicate that melatonin improved learning and memory deficits in APP695 transgenic mouse of Alzheimer's disease. An ovariectomized (OVX) rat model which is characterized by progressive memory deficits, central cholinergic nerve system degeneration and differentiation/apoptosis imbalance is the ideal in vivo model in which to test the neuroprotective effects of melatonin. ⋯ These findings demonstrate the important effects of melatonin and E2 on cholinergic neurons and support the potential application of melatonin in the treatment of dementia in postmenopausal women. Our results indicate that neuroprotection by melatonin partly correlated to modulation of apoptosis and protection of the cholinergic system. Early long-term melatonin application is a promising strategy which could potentially be applied in a clinic setting.