Sinha J K, Ghosh S, Swain U, Giridharan N V, Raghunath M
National Institute of Nutrition (NIN), Tarnaka, Hyderabad 500007, India.
Jawaharlal Nehru Technological University (JNTU), Kukatpally, Hyderabad 500085, India.
Neuroscience. 2014 Jun 6;269:256-64. doi: 10.1016/j.neuroscience.2014.03.040. Epub 2014 Apr 5.
Wistar of the National Institute of Nutrition obese (WNIN/Ob) is a unique rat strain isolated and established at NIN, Hyderabad, India, in 1996, from its existing stock of Wistar rat colony (WNIN). This animal model exhibits all traits of metabolic syndrome and has a remarkably reduced lifespan (1.5 years as compared to 3 years in parental WNIN rats), albeit, the factors associated with premature aging are not well understood. Considering that oxidative stress and DNA damage are crucial players associated with senescence, we analyzed oxidative stress markers like lipid peroxidation and protein oxidation; DNA damage in terms of both single-stranded and double-stranded breaks and the activity of antioxidant enzymes: superoxide dismutase and catalase in brain regions of these animals. Our study revealed that the magnitude of oxidative stress and DNA damage in the neocortex and hippocampus of 3-month-old WNIN/Ob obese rats is as high as that seen in 15-month-old parental WNIN control rats. Concurrently, the antioxidant enzyme activity was significantly decreased. From these results, it can be concluded that increased oxidative stress-induced damage of macromolecules, probably due to reduced activity of antioxidant enzymes, is associated with premature aging in WNIN/Ob obese rats.
印度海得拉巴国家营养研究所的肥胖Wistar大鼠（WNIN/Ob）是1996年从该研究所现有的Wistar大鼠种群（WNIN）中分离并培育出的一种独特大鼠品系。这种动物模型呈现出代谢综合征的所有特征，寿命显著缩短（与亲代WNIN大鼠的3年寿命相比为1.5年），尽管与早衰相关的因素尚未完全明确。鉴于氧化应激和DNA损伤是与衰老相关的关键因素，我们分析了这些动物脑区的氧化应激标志物，如脂质过氧化和蛋白质氧化；单链和双链断裂方面的DNA损伤以及抗氧化酶超氧化物歧化酶和过氧化氢酶的活性。我们的研究表明，3个月大的WNIN/Ob肥胖大鼠新皮层和海马体中的氧化应激和DNA损伤程度与15个月大的亲代WNIN对照大鼠一样高。同时，抗氧化酶活性显著降低。从这些结果可以得出结论，抗氧化酶活性降低可能导致氧化应激诱导的大分子损伤增加，这与WNIN/Ob肥胖大鼠的早衰有关。
