Elevation of oxidative-damage biomarkers during aging in F2 hybrid mice: Protection by chronic oral intake of resveratrol |
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| Authors: | Yee Ting Wong Jan Gruber Andrew M Jenner Mary Pei-Ern Ng Runsheng Ruan Francis Eng Hock Tay |
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| Institution: | 1. Department of Food Science and Nutrition, Faculty of Agriculture, Kinki University, Nara, Japan;2. Department of Biomedical Engineering, Faculty of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan;1. Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;2. State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, China;3. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicines, Nanjing 211198, China;1. Centre of Inflammation and Metabolism, August Krogh Centre, August Krogh Building, Department of Biology, University of Copenhagen, Copenhagen, Denmark;2. Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA;1. Department of Biochemistry and Molecular Biology III, School of Medicine, Complutense University of Madrid, Avda. Complutense s/n. 28040 Madrid, Spain;2. Department of Physiology, School of Medicine, Complutense University of Madrid, Avda. Complutense s/n. 28040 Madrid, Spain;3. Instituto de Investigación Biomédica de Vigo (IBIV), Xerencia de Xestión Integrada de Vigo, SERGAS, Biomedical Research Unit, Hospital Rebullón (CHUVI), Vigo, Spain |
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| Abstract: | Resveratrol (RSV), a naturally occurring phytoalexin that can be found in red wine, berries, and peanuts, has been shown to extend both mean and maximum life span in model organisms. RSV has also been reported to shift the physiology of middle-aged mice on a high-calorie diet toward that of mice on a standard diet. These beneficial effects of RSV have been suggested to resemble caloric restriction. Our study in F2 four-way cross-hybrid mice was the first to evaluate the effects of aging and long-term RSV treatment (14.09 ± 3.4 mg/L in drinking water for 6 or 12 months) on biomarkers of oxidative damage to DNA, 8-hydroxy-2′-deoxyguanosine (8OHdG); lipid, 8-iso-prostaglandin2α (8-iso-PGF2α); and protein, protein carbonyl content (PCC). There was a significant age-dependent accumulation of oxidative damage to DNA, lipid, and protein as well as a clear increase in urine 8-iso-PGF2α levels in the majority of mouse tissues. Rates of age-dependent increases in damage biomarkers varied between tissues. Chronic RSV treatment elevated total RSV plasma levels and reduced the observed age-dependent accumulation of (1) 8OHdG in liver and heart, (2) 8-iso-PGF2α in heart and urine, and (3) PCC in liver and kidney. However, a 12-month RSV intake resulted in significant elevation of 8-iso-PGF2α and PCC in kidney. Our studies demonstrate that RSV treatment consistently attenuated oxidative damage in tissues where age-related oxidative damage accumulation was prominent, but also suggested that chronic RSV treatment may induce nephrotoxicity. |
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