Administration of Melatonin and Related Indoles Prevents Exercise-Induced Cellular Oxidative Changes in Rats

Hara, Masayuki; Iigo, Masayuki; Ohtani-Kaneko, Ritsuko; Nakamura, Naoko; Suzuki, Takuro; Reíter, Russel J.; Hirata, Kazuaki

doi:10.1159/000109113

Cited by 76 publications

(54 citation statements)

References 22 publications

(26 reference statements)

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“…Melatonin has proven equally effective in reducing oxidative damage in conditions where free radical involvement has been established; such situations include ischemia/reperfusion injury [22,111], biliary obstruction [59], ionizing radiation [110], etc. The antioxidative protection afforded by melatonin has also been observed in organisms as diverse as unicells [4] and mammals [34,93]. Thus, it would appear that resisting free radical damage is a feature of melatonin in many species, in all organs and against many radical and reactive species.…”

Section: Discussionmentioning

confidence: 98%

Actions of Melatonin in the Reduction of Oxidative Stress

et al. 2000

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Melatonin was discovered to be a direct free radical scavenger less than 10 years ago. Besides its ability to directly neutralize a number of free radicals and reactive oxygen and nitrogen species, it stimulates several antioxidative enzymes which increase its efficiency as an antioxidant. In terms of direct free radical scavenging, melatonin interacts with the highly toxic hydroxyl radical with a rate constant equivalent to that of other highly efficient hydroxyl radical scavengers. Additionally, melatonin reportedly neutralizes hydrogen peroxide, singlet oxygen, peroxynitrite anion, nitric oxide and hypochlorous acid. The following antioxidative enzymes are also stimulated by melatonin: superoxide dismutase, glutathione peroxidase and glutathione reductase. Melatonin has been widely used as a protective agent against a wide variety of processes and agents that damage tissues via free radical mechanisms.

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Section: Discussionmentioning

confidence: 98%

Actions of Melatonin in the Reduction of Oxidative Stress

et al. 2000

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“…When a melatonin molecule scavenges a H 2 O 2 , it transforms to form AFMK. Since melatonin sacrifices itself and does not participate in redox cycling after scavenging free radicals, not only does melatonin not consume the cellular basic reductive force, GSH, but it also preserves or even increases the content of GSH in tissues [92][93][94][95]. Melatonin has been shown to be devoid of prooxidative activity in a variety of experimental models [46,96,97].…”

Section: Classical Antioxidants and Melatoninmentioning

confidence: 99%

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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“…Ceraulo et al [48] have developed an experimental micellar model which could explain how melatonin may function in the scavenging of both aqueous and lipophilic radicals within cells. Conversely, melatonin's protective effects in some of these subcellular compartments may be due to its indirect antioxidative actions, e.g., stimulation of enzymes which promote the synthesis of other antioxidants [20,32] or metabolize reactive species to nonradical products [18,19,49], which account for melatonin's ability to protect some biomolecules from free radical destruction.…”

Section: Melatonin Protection Of Intracellular Biomoleculesmentioning

confidence: 99%

“…Additionally, melatonin changes the activities of enzymes which metabolize reactive species [18][19][20] and alters membrane fluidity [21,22] thereby reducing the ability of damaging species to attack macromolecules in this structure.…”

Section: Introductionmentioning

confidence: 99%

Pharmacology and Physiology of Melatonin in the Reduction of Oxidative Stress in vivo

et al. 2000

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This brief resume summarizes the evidence which shows that melatonin is a significant free radical scavenger and antioxidant at both physiological and pharmacological concentrations in vivo. Surgical removal of the pineal gland, a procedure which lowers endogenous melatonin levels in the blood, exaggerates molecular damage due to free radicals during an oxidative challenge. Likewise, providing supplemental melatonin during periods of massive free radical production greatly lowers the resulting tissue damage and dysfunction. In the current review, these findings are considered in terms of neurodegenerative diseases, cancer, ischemia/reperfusion injury and aging. Besides being a highly effective direct free radical scavenger and indirect antioxidant, melatonin has several features that make it of clinical interest. Thus, melatonin is readily absorbed when it is administered via any route, it crosses all morphophysiological barriers, e.g., blood-brain barrier and placenta, with ease, it seems to enter all parts of every cell where it prevents oxidative damage, it preserves mitochondrial function, and it has low toxicity. While blood melatonin levels are normally low, tissue levels of the indoleamine can be considerably higher and at some sites, e.g., in bone marrow cells and bile, melatonin concentrations exceed those in the blood by several orders of magnitude. What constitutes a physiological level of melatonin must be redefined in terms of the bodily fluid, tissue and subcellular compartment being examined.

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Administration of Melatonin and Related Indoles Prevents Exercise-Induced Cellular Oxidative Changes in Rats

Cited by 76 publications

References 22 publications

Actions of Melatonin in the Reduction of Oxidative Stress

Actions of Melatonin in the Reduction of Oxidative Stress

Significance of Melatonin in Antioxidative Defense System: Reactions and Products

Pharmacology and Physiology of Melatonin in the Reduction of Oxidative Stress in vivo

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