Differential Behaviour of Cell Membranes towards Iron-Induced Oxidative Damage and the Effects of Melatonin

Tang, Pei; Xu, Mingxing; Qian, Zhiyu

doi:10.1159/000109140

Cited by 11 publications

(9 citation statements)

References 24 publications

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“…On the basis of this, it would be predicted that melatonin would be more effective in protecting lipidrich cellular membranes from oxidative damage than it would cytosolic protein or nuclear DNA. While there is no doubt that in vivo melatonin significantly reduces lipid peroxidation in membranes induced by a wide variety of agents [38][39][40][41], it is also highly effective (and possibly more so) in reducing free radical damage to DNA [42][43][44][45][46]. This is consistent with the reported high concentrations of melatonin in the nuclei of cells [23,24].…”

Section: Melatonin Protection Of Intracellular Biomoleculessupporting

confidence: 64%

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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Section: Melatonin Protection Of Intracellular Biomoleculessupporting

confidence: 64%

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

et al. 2000

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“…Arachidonic acid was protected more efficiently than DHA and EPA at all the melatonin concentrations examined when rat liver microsomes were incubated with ascorbic acid [69], which is quite similar to our results (Figures 6 and 7). This phenomenon is linked to protection against lipid peroxidation, a remarkable ability of melatonin supported by its amphoteric nature as well as its ability to cross the blood-brain barrier (BBB) and enter into the central nervous system [70].…”

Section: Discussionsupporting

confidence: 90%

Alterations in Lipid Levels of Mitochondrial Membranes Induced by Amyloid-ß: A Protective Role of Melatonin

Rosales-Corral

López-Armas

Cruz-Ramos

et al. 2012

International Journal of Alzheimer's Disease

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Alzheimer pathogenesis involves mitochondrial dysfunction, which is closely related to amyloid-β (Aβ) generation, abnormal tau phosphorylation, oxidative stress, and apoptosis. Alterations in membranal components, including cholesterol and fatty acids, their characteristics, disposition, and distribution along the membranes, have been studied as evidence of cell membrane alterations in AD brain. The majority of these studies have been focused on the cytoplasmic membrane; meanwhile the mitochondrial membranes have been less explored. In this work, we studied lipids and mitochondrial membranes in vivo, following intracerebral injection of fibrillar amyloid-β (Aβ). The purpose was to determine how Aβ may be responsible for beginning of a vicious cycle where oxidative stress and alterations in cholesterol, lipids and fatty acids, feed back on each other to cause mitochondrial dysfunction. We observed changes in mitochondrial membrane lipids, and fatty acids, following intracerebral injection of fibrillar Aβ in aged Wistar rats. Melatonin, a well-known antioxidant and neuroimmunomodulator indoleamine, reversed some of these alterations and protected mitochondrial membranes from obvious damage. Additionally, melatonin increased the levels of linolenic and n-3 eicosapentaenoic acid, in the same site where amyloid β was injected, favoring an endogenous anti-inflammatory pathway.

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“…Green plants provide both oxygen and nutrients, and some of these nutrients are important antioxidants. In our opinion, in addition to the clinical applications of receptor-mediated actions [15,16,[109][110][111][112][113][114][115][116][117][118][119][120][121][122][123], the therapeutic potential of melatonin and analogs [38,[124][125][126] as an antioxidative protective agent [18,19,22,29,30,43,46,72,75,101,[127][128][129][130][131][132][133][134][135][136][137][138] should be further explored.…”

Section: Discussionmentioning

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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Differential Behaviour of Cell Membranes towards Iron-Induced Oxidative Damage and the Effects of Melatonin

Cited by 11 publications

References 24 publications

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

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

Alterations in Lipid Levels of Mitochondrial Membranes Induced by Amyloid-ß: A Protective Role of Melatonin

Significance of Melatonin in Antioxidative Defense System: Reactions and Products

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