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外周淋巴细胞8-羟基脱氧鸟苷水平与斯普拉格-道利大鼠组织氧化DNA损伤的年龄相关性增加相关。热量限制的保护作用。

Peripheral lymphocyte 8-OHdG levels correlate with age-associated increase of tissue oxidative DNA damage in Sprague-Dawley rats. Protective effects of caloric restriction.

作者信息

Wolf Federica I, Fasanella Silvia, Tedesco Beatrice, Cavallini Gabriella, Donati Alessio, Bergamini Ettore, Cittadini Achille

机构信息

Institute of General Pathology and Giovanni XXIII Cancer Research Center, School of Medicine, Catholic University of Sacred Heart, L.go F. Vito, 1 Rome, Italy.

出版信息

Exp Gerontol. 2005 Mar;40(3):181-8. doi: 10.1016/j.exger.2004.11.002. Epub 2004 Dec 2.

Abstract

8-hydroxy-deoxyguanosine adducts (8-OHdG), indices of oxidative DNA damage, were measured by immunohystochemistry with diaminobenzidine detection in the brain, skeletal muscle, heart, liver, tenuum mucosa and lymphocytes from young (4 months) and aged (24 months) Sprague-Dawley rats fed ad libitum or held on two different caloric restriction diets (alternate day ad libitum feeding or daily feeding with 40% reduced calories). In the absence of caloric restriction the levels of oxidative DNA damage increased as a function of age in all tissues examined, with a maximum approximately 3-fold increase being detected in the peripheral lymphocytes and the heart and a minimum approximately 2-fold increase being detected in the liver and brain tissues. Caloric restriction regimens effectively reduced age-dependent increase of oxidative DNA damage in all tissues examined; in particular, the brain and small intestine did not exhibit any age-related increase of oxidative DNA damage. We propose that the levels of 8-OHdG in peripheral lymphocytes may serve a biochemical index of age-related whole organism oxidative DNA damage. Immunohistochemistry might be exploited as a rapid and simple techniques for measuring lymphocytes oxidative DNA damage in large scale studies.

摘要

采用免疫组织化学法,以二氨基联苯胺为显色剂,检测随意进食或采用两种不同热量限制饮食(隔日随意进食或每日减少40%热量摄入)的年轻(4个月)和老年(24个月)斯普拉格-道利大鼠脑、骨骼肌、心脏、肝脏、肠黏膜及淋巴细胞中的8-羟基脱氧鸟苷加合物(8-OHdG),即氧化性DNA损伤指标。在无热量限制的情况下,所有检测组织中的氧化性DNA损伤水平均随年龄增长而升高,外周淋巴细胞和心脏中检测到的增幅最大,约为3倍,肝脏和脑组织中检测到的增幅最小,约为2倍。热量限制方案有效降低了所有检测组织中氧化性DNA损伤随年龄的增长;特别是,脑和小肠未出现任何与年龄相关的氧化性DNA损伤增加。我们认为外周淋巴细胞中的8-OHdG水平可能作为与年龄相关的全机体氧化性DNA损伤的生化指标。免疫组织化学可作为一种快速简便的技术,用于大规模研究中测量淋巴细胞氧化性DNA损伤。

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