How melatonin interacts with lipid bilayers: a study by fluorescence and ESR spectroscopies

Costa, Ernane José Xavier; Shida, Cláudio S.; Biaggi, Márcia Helena; Ito, Amando Siuiti; Lamy, M. Teresa

doi:10.1016/s0014-5793(97)01178-2

Cited by 112 publications

(85 citation statements)

References 20 publications

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“…Since then, hundreds of publications have confirmed this observation [18,19]. As a free radical scavenger melatonin exhibits several important properties: (1) It is both lipophilic and hydrophilic [20,21] and it passes all bio-barriers, e.g., blood-brain barrier and placenta, with ease. It is available to all tissues and organs, even those in the fetus [22].…”

Section: Melatoninmentioning

confidence: 94%

Significance of Melatonin in Antioxidative Defense System: Reactions and Products

et al. 2000

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Melatonin is a potent endogenous free radical scavenger, actions that are independent of its many receptor-mediated effects. In the last several years, hundreds of publications have confirmed that melatonin is a broad-spectrum antioxidant. Melatonin has been reported to scavenge hydrogen peroxide (H₂O₂), hydroxyl radical (HO·), nitric oxide (NO·), peroxynitrite anion (ONOO^–), hypochlorous acid (HOCl), singlet oxygen (¹O₂), superoxide anion (O₂^–·) and peroxyl radical (LOO·), although the validity of its ability to scavenge O₂^–· and LOO· is debatable. Regardless of the radicals scavenged, melatonin prevents oxidative damage at the level of cells, tissues, organs and organisms. The antioxidative mechanisms of melatonin seem different from classical antioxidants such as vitamin C, vitamin E and glutathione. As electron donors, classical antioxidants undergo redox cycling; thus, they have the potential to promote oxidation as well as prevent it. Melatonin, as an electron-rich molecule, may interact with free radicals via an additive reaction to form several stable end-products which are excreted in the urine. Melatonin does not undergo redox cycling and, thus, does not promote oxidation as shown under a variety of experimental conditions. From this point of view, melatonin can be considered a suicidal or terminal antioxidant which distinguishes it from the opportunistic antioxidants. Interestingly, the ability of melatonin to scavenge free radicals is not in a ratio of mole to mole. Indeed, one melatonin molecule scavenges two HO·. Also, its secondary and tertiary metabolites, for example, N¹-acetyl-N²-formyl-5-methoxykynuramine, N-acetyl-5-methoxykynuramine and 6-hydroxymelatonin, which are believed to be generated when melatonin interacts with free radicals, are also regarded as effective free radical scavengers. The continuous free radical scavenging potential of the original molecule (melatonin) and its metabolites may be defined as a scavenging cascade reaction. Melatonin also synergizes with vitamin C, vitamin E and glutathione in the scavenging of free radicals. Melatonin has been detected in vegetables, fruits and a variety of herbs. In some plants, especially in flowers and seeds (the reproductive organs which are most vulnerable to oxidative insults), melatonin concentrations are several orders of magnitude higher than measured in the blood of vertebrates. Melatonin in plants not only provides an alternative exogenous source of melatonin for herbivores but also suggests that melatonin may be an important antioxidant in plants which protects them from a hostile environment that includes extreme heat, cold and pollution, all of which generate free radicals.

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Section: Melatoninmentioning

confidence: 94%

Significance of Melatonin in Antioxidative Defense System: Reactions and Products

et al. 2000

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“…Unlike some other wellknown antioxidants that are exclusively lipid (e.g., vitamin E) or water (e.g., vitamin C) soluble and, therefore, exhibit a limited intracellular distribution, melatonin is amphiphilic allowing it to reduce dOH-mediated damage in both the lipid and aqueous subcellular compartments. Evidence has shown that melatonin is clearly highly soluble in a lipid-based medium (Costa et al 1997) and it has also been shown to dissolve in aqueous media (Shida et al 1994). Rather little is known concerning melatonin' s speci® c intracellular distribution or concentration, although the few studies that have been performed suggest that its deposition in diOE erent subcellular compartments is not Figure 3 In a pure chemical system, melatonin has been shown to directly interact with hydrogen peroxide (H 2 O 2 ) with the formation of N 1 -acetyl-N 2 -formyl-5-methoxykynuramine(AFMK).…”

Section: Melatonin : Direct Scavenging Actionsmentioning

confidence: 99%

Melatonin: reducing the toxicity and increasing the efficacy of drugs

Reíter¹,

Tan²,

Sainz³

et al. 2002

Journal of Pharmacy and Pharmacology

378

300

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Melatonin (N-acetyl-5-methoxytryptamine) is a molecule with a very wide phylogenetic distribution from plants to man. In vertebrates, melatonin was initially thought to be exclusively of pineal origin ; recent studies have shown, however, that melatonin synthesis may occur in a variety of cells and organs. The concentration of melatonin within body uids and subcellular compartments varies widely, with blood levels of the indole being lower than those at many other sites. Thus, when de ning what constitutes a physiological level of melatonin, it must be de ned relative to a speci c compartment. Melatonin has been shown to have a variety of functions, and research in the last decade has proven the indole to be both a direct free radical scavenger and indirect antioxidant. Because of these actions, and possibly others that remain to be de ned, melatonin has been shown to reduce the toxicity and increase the ef cacy of a large number of drugs whose side effects are well documented. Herein, we summarize the bene cial effects of melatonin when combined with the following drugs: doxorubicin, cisplatin, epirubicin, cytarabine, bleomycin, gentamicin, ciclosporin, indometacin, acetylsalicylic acid, ranitidine, omeprazole, isoniazid, iron and erythropoietin, phenobarbital, carbamazepine, haloperidol, caposide-50, morphine, cyclophosphamide and L-cysteine. While the majority of these studies were conducted using animals, a number of the investigations also used man. Considering the low toxicity of melatonin and its ability to reduce the side effects and increase the ef cacy of these drugs, its use as a combination therapy with these agents seems important and worthy of pursuit.

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“…For example, ·-tocopherol (vitamin E) and ascorbic acid (vitamin C) are exclusively soluble in lipid and aqueous media, respectively; thus, their direct free-radical-scavenging activity is limited to those portions of the cell in which they are located. On the other hand, while melatonin is highly lipid soluble [14], it has considerable aqueous solubility [15] as well. As a consequence, it is able to function as an antioxidant in virtually all parts of the cell and to protect membrane lipids, cytosolic proteins and nuclear DNA from oxidative damage [6].…”

Section: Melatonin and Antioxidant Defensementioning

confidence: 99%

The Oxidant/Antioxidant Network: Role of Melatonin

et al. 1999

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Melatonin is now known to be a multifaceted free radical scavenger and antioxidant. It detoxifies a variety of free radicals and reactive oxygen intermediates including the hydroxyl radical, peroxynitrite anion, singlet oxygen and nitric oxide. Additionally, it reportedly stimulates several antioxidative enzymes including glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and superoxide dismutase; conversely, it inhibits a prooxidative enzyme, nitric oxide synthase. Melatonin also crosses all morphophysiological barriers, e.g., the blood-brain barrier, placenta, and distributes throughout the cell; these features increase the efficacy of melatonin as an antioxidant. Melatonin has been shown to markedly protect both membrane lipids and nuclear DNA from oxidative damage. In every experimental model in which melatonin has been tested, it has been found to resist macromolecular damage and the associated dysfunction associated with free radicals.

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How melatonin interacts with lipid bilayers: a study by fluorescence and ESR spectroscopies

Cited by 112 publications

References 20 publications

Significance of Melatonin in Antioxidative Defense System: Reactions and Products

Significance of Melatonin in Antioxidative Defense System: Reactions and Products

Melatonin: reducing the toxicity and increasing the efficacy of drugs

The Oxidant/Antioxidant Network: Role of Melatonin

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