Melatonin, hydroxyl radical‐mediated oxidative damage, and aging: A hypothesis

Abstract

Melatonin is a very potent and efficient endogenous radical scavenger. The pineal indolamine reacts with the highly toxic hydroxyl radical and provides on-site protection against oxidative damage to biomolecules within every cellular compartment. Melatonin acts as a primary non-enzymatic antioxidative defense against the devastating actions of the extremely reactive hydroxyl radical. Melatonin and structurally related tryptophan metabolites are evolutionary conservative molecules principally involved in the prevention of oxidative stress in organisms as different as algae and rats. The rate of aging and the time of onset of age-related diseases in rodents can be retarded by the administration of melatonin or treatments that preserve the endogenous rhythm of melatonin formation. The release of excitatory amino acids such as glutamate enhances endogenous hydroxyl radical formation. The activation of central excitatory amino acid receptors suppress melatonin synthesis and is therefore accompanied by a reduced detoxification rate of hydroxyl radicals. Aged animals and humans are melatonin-deficient and more sensitive to oxidative stress. Experiments investigating the effects of endogenous excitatory amino acid antagonists and stimulants of melatonin biosynthesis such as magnesium may finally lead to novel therapeutic approaches for the prevention of degeneration and dysdifferentiation associated with diseases related to premature aging.

Dietary melatonin supplementation alters uteroplacental amino acid flux during intrauterine growth restriction in ewes

“…This would account for the dramatic differences in maternal and fetal concentrations of BCAA across our treatment groups. This alteration in AA release across the placenta due to melatonin supplementation may be independent of direct melatonergic pathways and could be related to the antioxidant properties of melatonin (Poeggeler et al, 1993;Juaniaux et al, 2006;Reiter et al, 2007), although further investigation is needed in this area of research.…”

Putative regulatory molecules in plants: evaluating melatonin

“…One reason for these problems is that melatonin is readily diffusible in both polar and nonpolar environments. This property is thought to allow melatonin to quickly diffuse throughout tissues and cells and is frequently cited as a distinguishing feature of melatonin [Poeggeler et al, 1993]. Furthermore, melatonin is labile in plant extracts because of its radical scavenging properties.…”

Aging and oxygen toxicity: Relation to changes in melatonin

“…Perhaps nowhere is this more obvious than in the brain which is not only particularly vulnerable to free radical attack, but the number of neurodegenerative conditions that have been theoretically linked to oxygen toxicity is extensive (10,24,36,37).…”

“…On the basis of these studies, there is obviously disagreement as to how effective melatonin is under in vitro conditions in detoxifying the LOO~ The indole, however, has been shown to be very effective in reducing lipid peroxidation induced by a variety of toxicants (10,56,57) and whether this is due to the direct or indirect antioxidative actions of melatonin remains to be resolved. The protection melatonin affords because it functions as a free radical scavenger and antioxidant has been speculated to relate to processes and diseases of aging (9,36,58).…”

“…Melatonin's potentially beneficial effects against the degenerative signs of aging relate not only to its free radical and antioxidant activities (9,36,47), but also to its ability to synchronize circadian rhythms (122) promote sleep (123), stimulate immune function (102), and to its general protective effect in cells (124) (Fig. 4).…”