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Journal ArticleDOI

Effect of exogenous melatonin on X-ray induced cellular toxicity in lymphatic tissue of Indian tropical male squirrel, Funambulus pennanti.

01 May 2008-International Journal of Radiation Biology (Int J Radiat Biol)-Vol. 84, Iss: 5, pp 363-374
TL;DR: Exogenous melatonin with its anti-apoptotic and antioxidant properties additively increased the immunity of the squirrels, by protecting their hematopoietic system and lymphoid organs against X-ray radiation induced cellular toxicity.
Abstract: Purpose: The radioprotective ability of melatonin was investigated in the Indian tropical rodent, Funambulus pennanti during its reproductively inactive phase (RIP) when peripheral melatonin is high and the animal is under the influence of environmental stresses. Materials and methods: Fifty male squirrels were divided into two sets of 25 each; with set 1 receiving 0.9% saline and set 2 receiving 25 mg melatonin/100 g body weight/day for four weeks during evening hours. Five saline-treated and five-melatonin treated squirrels were sacrificed at times of 4, 24, 48 and 72 hours following 2.06 Gy X-ray radiation. Remaining squirrels that were not exposed to X-ray were used as control and melatonin treated, respectively. Total leukocyte count (TLC) and lymphocyte count (LC) in peripheral blood and lipid peroxidation (LPO) status, superoxide dismutase (SOD) activity, total antioxidant status (TAS), apoptotic percentage on the basis of morphological changes and DNA fragmentation and caspase3 activity were measured in the spleens of squirrels. Results: Peripheral blood and spleens with higher intrinsic levels of environmental and X-radiation induced free radical generation had inhibited TLC, LC, SOD activity and TAS and increased LPO and apoptosis. Melatonin pre-treatment significantly reduced and altered the changes brought on by X-radiation. Conclusion: Exogenous melatonin with its anti-apoptotic and antioxidant properties additively increased the immunity of the squirrels, by protecting their hematopoietic system and lymphoid organs against X-ray radiation induced cellular toxicity.

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Citations
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Journal ArticleDOI
TL;DR: It is found that melatonin protects human and murine CD4+ T cells from apoptosis by inhibiting CD95 ligand mRNA and protein upregulation in response to TCR/CD3 stimulation and reveals a novel biochemical pathway that regulates the expression of CD 95 ligand and potentially other downstream targets of NFAT activation.
Abstract: Over the past 20 y, the hormone melatonin was found to be produced in extrapineal sites, including cells of the immune system. Despite the increasing data regarding the biological effects of melatonin on the regulation of the immune system, the effect of this molecule on T cell survival remains largely unknown. Activation-induced cell death plays a critical role in the maintenance of the homeostasis of the immune system by eliminating self-reactive or chronically stimulated T cells. Because activated T cells not only synthesize melatonin but also respond to it, we investigated whether melatonin could modulate activation-induced cell death. We found that melatonin protects human and murine CD4 + T cells from apoptosis by inhibiting CD95 ligand mRNA and protein upregulation in response to TCR/CD3 stimulation. This inhibition is a result of the interference with calmodulin/calcineurin activation of NFAT that prevents the translocation of NFAT to the nucleus. Accordingly, melatonin has no effect on T cells transfected with a constitutively active form of NFAT capable of migrating to the nucleus and transactivating target genes in the absence of calcineurin activity. Our results revealed a novel biochemical pathway that regulates the expression of CD95 ligand and potentially other downstream targets of NFAT activation.

54 citations


Cites background from "Effect of exogenous melatonin on X-..."

  • ...In the case of mature T lymphocytes, exogenous melatonin was able to diminish the cytotoxicity of x-ray irradiation (45) or idarubicin (46)....

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Journal ArticleDOI
TL;DR: Interestingly, both melatonin and vitamin D have been found to selectively radiosensitise cancer cells, which makes them promising adjuvants in radiotherapy.
Abstract: Ionizing radiation (IR) has found widespread application in modern medicine, including medical imaging and radiotherapy. As a result, both patients and healthcare professionals are exposed to various IR doses. To minimize the negative side effects of radiation associated with oxidative imbalance, antioxidant therapy has been considered. In this review, studies on the effects of melatonin and vitamin D on radiation-induced oxidative stress are discussed. According to the research data, both substances meet the conditions for use as agents that protect humans against IR-induced tissue damage. Numerous studies have confirmed that melatonin, a hydro- and lipophilic hormone with strong antioxidant properties, can potentially be used as a radioprotectant in humans. Less is known about the radioprotective effects of vitamin D, but the results to date have been promising. Deficiencies in melatonin and vitamin D are common in modern societies and may contribute to the severity of adverse side effects of medical IR exposure. Hence, supporting supplementation with both substances seems to be of first importance. Interestingly, both melatonin and vitamin D have been found to selectively radiosensitise cancer cells, which makes them promising adjuvants in radiotherapy. More research is needed in this area, especially in humans.

48 citations

Journal Article
01 Jan 2013-Cell
TL;DR: It is suggested that administration of melatonin before and after irradiation may reduce liver damage caused by gamma irradiation, and Hepatic MDA levels in irradiated rats that were treated with melatonin were significantly decreased, while GSH levels were significantly increased, when compared to either of the control groups or the melatonin only group.

43 citations


Cites background from "Effect of exogenous melatonin on X-..."

  • ...organs including the spleen (8, 11, 22), liver (5, 9, 20),...

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  • ...Melatonin (N-acetyl-5-methoxytryptamine) is an endogenous compound synthesized by the pineal gland in the human brain (10-12)....

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Journal ArticleDOI
TL;DR: Pre-treatment with melatonin (10 mg/kg) is likely to be a threshold concentration for significant protection against lower dose of 2 Gy gamma irradiation compared to higher dose of 8 Gy, therefore it seems that radio-protective effects of melatonin are dose-dependent.

41 citations


Cites background from "Effect of exogenous melatonin on X-..."

  • ...06 Gy X-ray-induced cellular toxicity [31]....

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  • ...spinal cord [24e26], lens [27], liver [28e30], spleen [2,31,32], lung, colon and ileum [29]....

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  • ...[2,31,32] studies when reported that pre-treatment with melatonin increased lymphocyte count in irradiated groups....

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Journal ArticleDOI
TL;DR: How circadian rhythms regulate and synchronize adult stem cell functions and how alterations in clock function during aging modulate the extrinsic and intrinsic mechanisms that determine adult stem cells homeostasis are discussed.

37 citations

References
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Journal ArticleDOI
TL;DR: A method for the screening of antioxidant activity is reported as a decolorization assay applicable to both lipophilic and hydrophilic antioxidants, including flavonoids, hydroxycinnamates, carotenoids, and plasma antioxidants.

18,580 citations


"Effect of exogenous melatonin on X-..." refers methods in this paper

  • ...The radical scavenging activity of antioxidants for ABTS radical cations was measured according to the method of Re et al. (1999)....

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Journal ArticleDOI
TL;DR: The extent of tissue-PCD revealed by this method is considerably greater than apoptosis detected by nuclear morphology, and thus opens the way for a variety of studies.
Abstract: Programmed cell death (PCD) plays a key role in developmental biology and in maintenance of the steady state in continuously renewing tissues. Currently, its existence is inferred mainly from gel electrophoresis of a pooled DNA extract as PCD was shown to be associated with DNA fragmentation. Based on this observation, we describe here the development of a method for the in situ visualization of PCD at the single-cell level, while preserving tissue architecture. Conventional histological sections, pretreated with protease, were nick end labeled with biotinylated poly dU, introduced by terminal deoxy-transferase, and then stained using avidin-conjugated peroxidase. The reaction is specific, only nuclei located at positions where PCD is expected are stained. The initial screening includes: small and large intestine, epidermis, lymphoid tissues, ovary, and other organs. A detailed analysis revealed that the process is initiated at the nuclear periphery, it is relatively short (1-3 h from initiation to cell elimination) and that PCD appears in tissues in clusters. The extent of tissue-PCD revealed by this method is considerably greater than apoptosis detected by nuclear morphology, and thus opens the way for a variety of studies.

9,597 citations


"Effect of exogenous melatonin on X-..." refers methods in this paper

  • ...OH DNA ends accompanying chromatin fragmentation can be detected by the TUNEL assay (Gavrieli et al. 1992)....

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  • ...Free 30-OH DNA ends accompanying chromatin fragmentation can be detected by the TUNEL assay (Gavrieli et al. 1992)....

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Journal ArticleDOI
TL;DR: This report reviews the studies which document the influence of melatonin on the activity and expression of the antioxidative enzymes glutathione peroxidase, superoxide dismutases and catalase both under physiological and under conditions of elevated oxidative stress and analyses the possible mechanisms by which melatonin regulates these enzymes.
Abstract: Antioxidant enzymes form the first line of defense against free radicals in organisms. Their regulation depends mainly on the oxidant status of the cell, given that oxidants are their principal modulators. However, other factors have been reported to increase antioxidant enzyme activity and/or gene expression. During the last decade, the antioxidant melatonin has been shown to possess genomic actions, regulating the expression of several genes. Melatonin also influences both antioxidant enzyme activity and cellular mRNA levels for these enzymes. In the present report, we review the studies which document the influence of melatonin on the activity and expression of the antioxidative enzymes glutathione peroxidase, superoxide dismutases and catalase both under physiological and under conditions of elevated oxidative stress. We also analyze the possible mechanisms by which melatonin regulates these enzymes.

1,824 citations


"Effect of exogenous melatonin on X-..." refers background in this paper

  • ...Melatonin regulates antioxidant enzyme gene expression and activity with activation of MT1/2 receptors, via G inhibitory (Gi) protein (Mayo et al. 2002, Rodriguez et al. 2004)....

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  • ...…discovery of melatonin as a direct free radical scavenger (Tan et al. 1993) and as an indirect antioxidant via its stimulatory actions on antioxidative enzymes (Reiter et al. 2000, Rodriguez et al. 2004) has greatly increased interest in the use of this agent in experimental and clinical settings....

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  • ...The oxidative status of the cell is the primary factor regulating gene expression and activity of these enzymes (Rodriguez et al. 2004)....

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Journal ArticleDOI
TL;DR: Melatonin was discovered to be a direct free radical scavenger less than 10 years ago and 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.
Abstract: 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.

1,074 citations


"Effect of exogenous melatonin on X-..." refers background in this paper

  • ...…discovery of melatonin as a direct free radical scavenger (Tan et al. 1993) and as an indirect antioxidant via its stimulatory actions on antioxidative enzymes (Reiter et al. 2000, Rodriguez et al. 2004) has greatly increased interest in the use of this agent in experimental and clinical settings....

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