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The protective effects of vitamin C on the DNA damage,antioxidant defenses and aorta histopathology in chronic hyperhomocysteinemia induced rats
Affiliation:1. Department of Radiation Oncology, Tungs'' Taichung Metro Harbor Hospital, Taichung, Taiwan;2. Division of Radiotherapy, Cheng Hsin General Hospital, Taipei, Taiwan;3. School of Medicine, National Yang-Ming University, Taipei, Taiwan;4. Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan;5. Department of Hemato-Oncology, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan;6. Cardiovascular Center and Department of Anesthesiology, Taichung Veteran General Hospital, Taichung, Taiwan;7. Department of Radiation Oncology, Taipei Medical University and Hospital, Taipei, Taiwan;8. Department of Radiation Oncology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;1. HeartDrug Research Laboratories, Johns Hopkins University, Osler Medical Building, 7600 Osler Drive, Suite 307, Towson, MD, 21204, United States;2. Wegmans Pharmacy, Ithaca, NY, United States;3. Bagcılar Research and Education Hospital, Cardiology Department, Bagcılar, Istanbul, Turkey;4. Department of Molecular Pharmacology & Radiobiology, Pirogov Russian National Research Medical University, Moscow, Russia;5. Neurology Department, Charles University, 2nd School of Medicine, Prague, Czech Republic
Abstract:The aim of this study was to investigate the protective effect of vitamin C towards hyperhomocysteinemia (hHcy) induced oxidative DNA damage using the comet assay. The increase in plasma homocysteine levels is an important risk factor for vascular and cardiovascular diseases through free radical production. This study was also conducted to investigate the histopathological changes in the thoracic aorta and the oxidant/antioxidant status in heart, liver and kidney tissues.Twenty-four adult male Wistar rats were divided as control, hHcy and hHcy + vitamin C group. Chronic hHcy was induced by oral administration of l-methionine (1 g/kg/day) for 28 days. Vitamin C was given 150 mg/kg/day within the specified days. DNA damage was measured by use of the comet assay in lymphocytes. Levels of malondialdehyde (MDA) and glutathione (GSH) as well as catalase (CAT) and superoxide dismutase (SOD) activities were determined in heart, liver and renal tissues.Results show that l-methionine administration significantly increased % Tail DNA and Mean Tail Moment in hHcy group as compared with other groups. Vitamin C treatment significantly decreased the high MDA levels and increased activity of antioxidant enzymes in tissues. Aortic diameter and thickness of aortic elastic laminae were significantly lower in hHcy + vitamin C group.Comet assay can be used for the assessment of primary DNA damage caused by hHcy. Histopathological findings showed that vitamin C may have a preventive effect in alleviating the negative effects of hHcy. Vitamin C might be useful in the prevention of endothelial dysfunction caused by hHcy.
Keywords:Hyperhomocysteinemia  Vitamin C  Comet assay  Lymphocyt  Oxidative stress  Rats
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