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      Protective Effect of Melatonin Against Mitomycin C-Induced Genotoxic Damage in Peripheral Blood of Rats

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          Abstract

          Mitomycin C (MMC) generates free radicals when metabolized. We investigated the effect of melatonin against MMC-induced genotoxicity in polychromatic erythrocytes and MMC-induced lipid peroxidation in brain and liver homogenates. Rats ( N = 36) were classified into 4 groups: control, melatonin, MMC, and MMC + melatonin. Melatonin and MMC doses of 10 mg/kg and 2 mg/kg, respectively, were injected intraperitoneally. Peripheral blood samples were collected at 0, 24, 48, 72, and 96 hours posttreatment and homogenates were obtained at 96 hours posttreatment. The number of micronucleated polychromatic erythrocytes (MN-PCE) per 1000 PCE was used as a genotoxic marker. Malondialdehyde (MDA) plus 4-hydroxyalkenal (4-HDA) levels were used as an index of lipid peroxidation. The MMC group showed a significant increase in MN-PCE at 24, 48, 72, and 96 hours that was significantly reduced with melatonin begin coadministrated. No significant differences were found in lipid peroxidation. Our results indicate that MMC-induced genotoxicity can be reduced by melatonin.

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          Most cited references 66

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          Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury.

          Increasing appreciation of the causative role of oxidative injury in many disease states places great importance on the reliable assessment of lipid peroxidation. Malondialdehyde (MDA) is one of several low-molecular-weight end products formed via the decomposition of certain primary and secondary lipid peroxidation products. At low pH and elevated temperature, MDA readily participates in nucleophilic addition reaction with 2-thiobarbituric acid (TBA), generating a red, fluorescent 1:2 MDA:TBA adduct. These facts, along with the availability of facile and sensitive methods to quantify MDA (as the free aldehyde or its TBA derivative), have led to the routine use of MDA determination and, particularly, the "TBA test" to detect and quantify lipid peroxidation in a wide array of sample types. However, MDA itself participates in reactions with molecules other than TBA and is a catabolic substrate. Only certain lipid peroxidation products generate MDA (invariably with low yields), and MDA is neither the sole end product of fatty peroxide formation and decomposition nor a substance generated exclusively through lipid peroxidation. Many factors (e.g., stimulus for and conditions of peroxidation) modulate MDA formation from lipid. Additional factors (e.g., TBA-test reagents and constituents) have profound effects on test response to fatty peroxide-derived MDA. The TBA test is intrinsically nonspecific for MDA; nonlipid-related materials as well as fatty peroxide-derived decomposition products other than MDA are TBA positive. These and other considerations from the extensive literature on MDA. TBA reactivity, and oxidative lipid degradation support the conclusion that MDA determination and the TBA test can offer, at best, a narrow and somewhat empirical window on the complex process of lipid peroxidation. The MDA content and/or TBA reactivity of a system provides no information on the precise structures of the "MDA precursor(s)," their molecular origins, or the amount of each formed. Consequently, neither MDA determination nor TBA-test response can generally be regarded as a diagnostic index of the occurrence/extent of lipid peroxidation, fatty hydroperoxide formation, or oxidative injury to tissue lipid without independent chemical evidence of the analyte being measured and its source. In some cases, MDA/TBA reactivity is an indicator of lipid peroxidation; in other situations, no qualitative or quantitative relationship exists among sample MDA content, TBA reactivity, and fatty peroxide tone. Utilization of MDA analysis and/or the TBA test and interpretation of sample MDA content and TBA test response in studies of lipid peroxidation require caution, discretion, and (especially in biological systems) correlative data from other indices of fatty peroxide formation and decomposition.
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            Melatonin: from basic research to cancer treatment clinics.

            Melatonin, the chief secretory product of the pineal gland, is a direct free radical scavenger, an indirect antioxidant, as well as an important immunomodulatory agent. In both in vitro and in vivo investigations, melatonin protected healthy cells from radiation-induced and chemotherapeutic drug-induced toxicity. Furthermore, several clinical studies have demonstrated the potential of melatonin, either alone or in combination with traditional therapy, to yield a favorable efficacy to toxicity ratio in the treatment of human cancers. This study reviews the literature from laboratory investigations that document the antioxidant and oncostatic actions of melatonin and summarizes the evidence regarding the potential use of melatonin in cancer treatment. This study also provides rationale for the design of larger translational research-based clinical trials.
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              Oxidative stress of the newborn in the pre- and postnatal period and the clinical utility of melatonin.

              Newborns, and especially those delivered preterm, are probably more prone to oxidative stress than individuals later in life. Also during pregnancy, increased oxygen demand augments the rate of production of reactive oxygen species (ROS) and women, even with normal pregnancies, experience elevated oxidative stress and lipid peroxidation compared with nonpregnant women. Also, there appears to be an increase in ROS generation in the placenta of pre-eclamptic women. In comparison with healthy adults, newborn infants have lower levels of plasma antioxidants such as vitamin E, beta-carotene, and sulphydryl groups, lower levels of plasma metal binding proteins including ceruloplasmin and transferrin, and reduced activity of erythrocyte superoxide dismutase. This review summarizes conditions of newborns where there is elevated oxidative stress. Included in this group of conditions is asphyxia, respiratory distress syndrome and sepsis and the review also summarizes the literature related to clinical trials of antioxidant therapies and of melatonin, a highly effective antioxidant and free radical scavenger. The authors document there is general agreement that short-term melatonin therapy may be highly effective and that it has a remarkably benign safety profile, even when neonates are treated with pharmacological doses. Significant complications with long-term melatonin therapy in children and adults also have not been reported. None of the animal studies of maternal melatonin treatment or in postnatal life have shown any treatment-related side effects. The authors conclude that treatment with melatonin might result in a wide range of health benefits, improved quality of life and reduced healthcare costs and may help reduce complications in the neonatal period.
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                Author and article information

                Journal
                J Biomed Biotechnol
                JBB
                Journal of Biomedicine and Biotechnology
                Hindawi Publishing Corporation
                1110-7243
                1110-7251
                2009
                20 October 2009
                : 2009
                Affiliations
                1Department of Pharmacology and Physiology, University of Zaragoza, 50009 Zaragoza, Spain
                2Departments of Neurology and Medicine, Medical College of Wisconsin, Milwaakee, WI 53226, USA
                3Department of Family and Community Medicine, Medical College of Wisconsin, Milwaakee, WI 53226, USA
                4Department of Human Anatomy and Histology, University of Zaragoza, 50009 Zaragoza, Spain
                Author notes

                Recommended by Gary S. Stein

                Article
                10.1155/2009/791432
                2764378
                19859567
                Copyright © 2009 S. Ortega-Gutiérrez et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Research Article

                Molecular medicine

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