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      Modulation of immunity in young-adult and aged squirrel, Funambulus pennanti by melatonin and p-chlorophenylalanine

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      Immunity & Ageing : I & A
      BioMed Central

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          Abstract

          Background

          Our interest was to find out whether pineal gland and their by melatonin act as modulator of immunosenescence. Parachlorophenylalanine (PCPA) – a β adrenergic blocker, is known to perform chemical pinealectomy (Px) by suppressing indirectly the substrate 5-hydroxytryptamine (5-HT) for melatonin synthesis and thereby melatonin itself. The role of PCPA, alone and in combination with melatonin was recorded in immunomodulation and free radical load in spleen of young adult and aged seasonal breeder Indian palm squirrel Funambulus pennanti.

          Results

          Aged squirrel presented reduced immune parameters (i.e. total leukocyte count (TLC), Lymphocytes Count (LC), % stimulation ratio of splenocytes (% SR) against T cell mitogen concanavalin A (Con A), delayed type hypersensitivity (DTH) to oxazolone) when compared to young adult group. Melatonin administration (25 μg/100 g body mass/day) significantly increased the immune parameters in aged more than the young adult squirrel while PCPA administration (4.5 mg/100 g body mass/day) reduced all the immune parameters more significantly in young than aged. Combination of PCPA and melatonin significantly increased the immune parameters to the normal control level of both the age groups. TBARS level was significantly high in aged than the young group. PCPA treatment increased TBARS level of young and aged squirrels both while melatonin treatment decreased it even than the controls. Nighttime peripheral melatonin level was low in control aged group than the young group. Melatonin injection at evening hours significantly increased the peripheral level of nighttime melatonin, while combined injection of PCPA and melatonin brought it to control level in both aged and young adult squirrels.

          Conclusion

          PCPA suppressed immune status more in aged than in adult by reducing melatonin level as it did chemical Px. Melatonin level decreased in control aged squirrels and so there was a decrease in immune parameters with a concomitant increase in free radical load of spleen. Decreased immune status can be restored following melatonin injection which decreased free radical load of spleen and suggest that immune organs of aged squirrels were sensitive to melatonin. Increased free radical load and decreased peripheral melatonin could be one of the reasons of immunosenescence.

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          Most cited references37

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          Regulation of antioxidant enzymes: a significant role for melatonin.

          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.
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            • Abstract: not found
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            Seasonal immune function and sickness responses.

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              Melatonin and its relation to the immune system and inflammation.

              Melatonin (N-acetyl-5-methoxytryptamine) was initially thought to be produced exclusively in the pineal gland. Subsequently its synthesis was demonstrated in other organs, for example, the retinas, and very high concentrations of melatonin are found at other sites, for example, bone marrow cells and bile. The origin of the high level of melatonin in these locations has not been definitively established, but it is likely not exclusively of pineal origin. Melatonin has been shown to possess anti-inflammatory effects, among a number of actions. Melatonin reduces tissue destruction during inflammatory reactions by a number of means. Thus melatonin, by virtue of its ability to directly scavenge toxic free radicals, reduces macromolecular damage in all organs. The free radicals and reactive oxygen and nitrogen species known to be scavenged by melatonin include the highly toxic hydroxyl radical (.OH), peroxynitrite anion (ONOO-), and hypochlorous acid (HOCl), among others. These agents all contribute to the inflammatory response and associated tissue destruction. Additionally, melatonin has other means to lower the damage resulting from inflammation. Thus, it prevents the translocation of nuclear factor-kappa B (NF-kappa B) to the nucleus and its binding to DNA, thereby reducing the upregulation of a variety of proinflammatory cytokines, for example, interleukins and tumor neurosis factor-alpha. Finally, there is indirect evidence that melatonin inhibits the production of adhesion molecules that promote the sticking of leukocytes to endothelial cells. By this means melatonin attenuates transendothelial cell migration and edema, which contribute to tissue damage.
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                Author and article information

                Journal
                Immun Ageing
                Immunity & Ageing : I & A
                BioMed Central
                1742-4933
                2009
                23 April 2009
                : 6
                : 5
                Affiliations
                [1 ]Department of Zoology, Pineal Research Lab, Banaras Hindu University, Varanasi – 221005, India
                Article
                1742-4933-6-5
                10.1186/1742-4933-6-5
                2689854
                19389248
                2f674565-f438-4f90-b878-fb23198aea11
                Copyright © 2009 Rai et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 December 2008
                : 23 April 2009
                Categories
                Research

                Immunology
                Immunology

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