CommentariesAntioxidant properties of melatonin—an emerging mystery
Section snippets
Physiology, synthesis, and metabolism of melatonin
The pineal gland secretes an indoleamide called melatonin, so named because it has the ability in certain fish, reptiles, and amphibians to temporarily turn the skin a dark color (produced by the chemical pigment melanin) [8]. In the human brain, the pineal gland is located on the dorsal surface of the hypothalamus, occupying a central position between the two cerebral hemispheres [1]. The highly vascularized tissue of the pineal gland consists of two types of cells: pinealocytes and neuroglia.
Melatonin receptors and mechanisms of action
Two pharmacologically distinct families of membrane-bound melatonin receptors known as ML1 and ML2 have been identified. Using the potent melatonin agonist 2-[125I]iodomelatonin, the ML1 receptors have been shown to be high-affinity receptors with a Kd of ∼75 pM in chick and rabbit retina [14]. In contrast, the ML2 receptors have a lower affinity for the same melatonin receptor agonist (Kd > 2 nM in hamster brain; > 1 nM in human brain) [14]. The genes encoding the human melatonin receptors,
Clinical applications of melatonin
It is quite apparent that the hormonal role for melatonin is functionally related to neuroendocrine physiology, with a strong association also existing between its secretion and the normal occurrence of sleep and (other) circadian rhythms. The onset of normal sleep is characterized by a rapid increase in melatonin concentrations, and it is believed that the overall quality of sleep is contingent upon the natural oscillating pattern of melatonin secretion [13]. In this regard, it is interesting
Melatonin as an antioxidant
Oxygen comprises 21% of the earth’s atmosphere [39] and is essential for the life of aerobic organisms. However, a major paradox is that oxygen, in certain states, can be lethal to the body tissue of organisms that depend on it for life. The majority of oxygen inspired is used to generate energy in the form of ATP 39, 40. However, a relatively large amount—approximately 5%—of inspired oxygen is converted to free radicals, many of which are extremely toxic [7]. A certain cause of age-related
Conclusion
The biosynthesis of melatonin is largely regulated by the photoperiodic environment. Although the circadian and endocrine effects of melatonin are moderately well understood, the potential role that melatonin plays as a free radical scavenger is only beginning to surface. As our geriatric population continues to grow, so does the incidence of neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease, the primary dementia in modern society. Furthermore, as people age, they
References (59)
- et al.
Melatonin madness
Cell
(1995) - et al.
Circadian clock functions localized in Xenopus retinal photoreceptors
Neuron
(1993) - et al.
Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses
Neuron
(1994) - et al.
The significance of the metabolism of the neurohormone melatoninAntioxidative protection and formation of bioactive substances
Neurosci Biobehav Rev
(1993) - et al.
Rhythmic transcriptionThe molecular basis of circadian melatonin synthesis
Trends Neurosci
(1997) - et al.
Fall in nocturnal serum melatonin during prepuberty and pubescence
Lancet
(1984) Melatonin receptorsAre there multiple subtypes?
Trends Pharmacol Sci
(1995)- et al.
Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock
Neuron
(1997) - et al.
The melatonin receptor in the human brainCloning experiments and distribution studies
Mol Brain Res
(1996) - et al.
Impaired nocturnal secretion of melatonin in coronary heart disease
Lancet
(1995)
Endocrine and immune effects of melatonin therapy in metastatic cancer patients
Eur J Cancer Clin Oncol
Melatonin protects human blood lymphocytes from radiation-induced chromosome damage
Mutat Res
Melatonin administration attenuates depressed immune functions after trauma-hemorrhage
J Surg Res
Pharmacological actions of melatonin in oxygen radical pathophysiology
Life Sci
Oxidants as stimulators of signal transduction
Free Radic Biol Med
Redox signalingNitrosylation and related target interactions of nitric oxide
Cell
Deleterious network hypothesis of aging
Med Hypotheses
The pineal hormone melatonin inhibits DNA–adduct formation induced by the chemical carcinogen safrole in vivo
Cancer Lett
H2O2-induced lipid peroxidation in rat brain homogenates is greatly reduced by melatonin
Neurosci Lett
Evaluation of the antioxidant activity of melatonin in vitro
Free Radic Biol Med
Melatonin prevents bovine cerebral endothial cells from hyperoxia-induced DNA damage and death
Neurosci Lett
Reaction of melatonin and related indoles with hydroxyl radicalsEPR and spin trapping investigations
Free Radic Biol Med
Melatonin in humans
N Engl J Med
Pineal control of agingEffect of melatonin and pineal grafting on aging mice
Proc Natl Acad Sci USA
Functional aspects of the pineal hormone melatonin in combating cell and tissue damage induced by free radicals
Eur J Endocrinol
The decrease of pineal melatonin production with age
Ann NY Acad Sci
Cited by (132)
Suggesting a prospect for melatonin-mediated orchid flowering under extreme conditions
2023, Scientia HorticulturaeActivation of SIRT1/PGC 1α/SIRT3 pathway by melatonin provides protection against mitochondrial dysfunction in isoproterenol induced myocardial injury
2020, HeliyonCitation Excerpt :hydrogen peroxide (H2O2), hydroxyl radical (. OH) [15, 16] along with up-regulating antioxidant enzymes and down-regulating pro-oxidant enzymes [17, 18]. Melatonin also chelates metal ions [19] and prevents electron leakage from ETC [20].
Waterproof paper as a new substrate to construct a disposable sensor for the electrochemical determination of paracetamol and melatonin
2020, TalantaCitation Excerpt :It has also been believed that sleep quality is directly related to oscillation for MEL concentration [29]. This association contributed to the recent public interest, since this may help in a better quality of sleep, especially in jet leg cases [30]. The impacts of the hard use of pharmaceuticals have been attracted interest, mainly investigating the effects of these compounds in human, animal and environmental health [31].
Melatonin: Protection against age-related cardiac pathology
2017, Ageing Research ReviewsCitation Excerpt :Interestingly, aging is associated with a significant reduction in endogenous melatonin secretion (Karasek and Reiter, 2002), resulting in an augmentation of oxidative stress and other metabolic changes (Bubenik and Konturek, 2011; Espino et al., 2012; Hill et al., 2013). Melatonin is well known as a potent scavenger of reactive oxygen species, such as hydroxyl radical, peroxyl radical, superoxide anion radical and hydrogen peroxide (Al-Omary, 2013; Allegra et al., 2003; Beyer et al., 1998; Cuzzocrea et al., 1997; Favero et al., 2014; Galano et al., 2013; Ramis et al., 2015 Ramis et al., 2015). Melatonin is also known as an indirect antioxidant agent due to its ability to up-regulate antioxidant enzymes and down-regulate pro-oxidant enzymes (Domínguez-Rodríguez et al., 2002, 2009; Halladin et al., 2014a; Reiter et al., 2001a, 2016; Rodriguez et al., 2004; Tan et al., 2001).
Melatonin-loaded silica coated with hydroxypropyl methylcellulose phthalate for enhanced oral bioavailability: Preparation, and in vitro-in vivo evaluation
2017, European Journal of Pharmaceutics and BiopharmaceuticsCitation Excerpt :MLT is a natural product synthesized by the pineal gland of mammals [1].
A mid-pandemic night's dream: Melatonin, from harbinger of anti-inflammation to mitochondrial savior in acute and long COVID-19 (Review)
2024, International Journal of Molecular Medicine