Luceri Cristina, Bigagli Elisabetta, Femia Angelo Pietro, Caderni Giovanna, Giovannelli Lisa, Lodovici Maura
Department of NEUROFARBA, Section of Pharmacology and Toxicology, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
Toxicol Rep. 2017 Dec 21;5:141-145. doi: 10.1016/j.toxrep.2017.12.017. eCollection 2018.
Oxidative stress, defined as an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense mechanisms, plays a major role in inducing oxidative damage and cellular impairment, resulting in a general decline of the physiological functions. The aim of this work was to evaluate age-related changes in circulating ROS levels and plasma protein carbonyls, in very young (2 months aged), young (8 months aged) and in middle age (15 months aged) F344 rats. In addition, the DNA oxidative marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the expression of the DNA repair enzymes and genes were also measured in the liver of these animals. We also determined whether systemic oxidative stress reflects oxidative injury at organ level. Our results demonstrate that the increase in circulating ROS and protein carbonyl content occurs as early as middle age. Moreover, increased 8-OHdG in the liver of 15-month-old rats was at least in part associated with a reduced DNA damage repairing capacity as suggested by the down-regulation of gene expression. In addition, we demonstrated for the first time, that plasma carbonyls and liver 8-OHdG are well correlated, suggesting that plasma protein carbonyls may be used as a surrogate marker of oxidative injury in target organs.
氧化应激被定义为活性氧(ROS)产生与抗氧化防御机制之间的失衡,在诱导氧化损伤和细胞功能障碍中起主要作用,导致生理功能普遍下降。本研究的目的是评估2月龄幼龄、8月龄青年和15月龄中年F344大鼠循环ROS水平和血浆蛋白羰基的年龄相关变化。此外,还检测了这些动物肝脏中的DNA氧化标志物8-羟基-2'-脱氧鸟苷(8-OHdG)以及DNA修复酶和基因的表达。我们还确定了全身氧化应激是否反映器官水平的氧化损伤。我们的结果表明,循环ROS和蛋白羰基含量的增加早在中年就已出现。此外,15月龄大鼠肝脏中8-OHdG的增加至少部分与基因表达下调所提示的DNA损伤修复能力降低有关。此外,我们首次证明,血浆羰基与肝脏8-OHdG高度相关,表明血浆蛋白羰基可用作靶器官氧化损伤的替代标志物。