Zafir Ayesha, Banu Naheed
Department of Biochemistry, Faculty of Life Sciences, A. M. University, Aligarh, UP, India.
Stress. 2009 Mar;12(2):167-77. doi: 10.1080/10253890802234168.
Physical and psychological stressors not only enhance activity of the hypothalamo-pituitary-adrenocortical axis, but also cause oxidative damage by inducing an imbalance between the in vivo pro-oxidant and antioxidant status. The involvement of adrenal steroid stress hormones in oxidative damage associated with these stressors has not been extensively investigated. Therefore, this study was designed to probe any direct role of glucocorticoids on induction of oxidative processes by comparing the effects of low, intermediate and high doses of exogenously administered corticosterone, without other applied stressors, on a wide range of key components of the antioxidant defence system. The data presented here indicate a substantial decline in antioxidant defences by actions of corticosterone, evidenced by coordinate decreases in the activities in the brain, liver and heart of free-radical scavenging enzymes superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and glutathione reductase (GR), as well as the non-enzymatic antioxidants glutathione (GSH) and serum urate. Also, lipid peroxidation and protein carbonyl contents, oxidative stress markers, were found to be significantly increased in brain, liver and heart. The compromised in vivo antioxidant status was strikingly analogous to the deleterious effects of restraint stress, indicating a direct effect of stress hormones on induction of oxidative damage during physical or psychological stress. A dose-dependent decrease of SOD and CAT, and increase in protein oxidation was observed between the high (40 mg/kg) and low (10 mg/kg) doses of corticosterone. The findings have fundamental implications for oxidative stress as a major pathological mechanism in the maladaptation to chronic stress. Thus, the study suggests that stress hormones have a causal role in impacting oxidative processes induced during the adaptive response. This may hold important implications for pharmacological interventions targeting cellular antioxidants as a promising strategy for protecting against oxidative insults in various psychiatric and non-psychiatric conditions induced by physical or psychological stress.
生理和心理应激源不仅会增强下丘脑 - 垂体 - 肾上腺皮质轴的活性，还会通过诱导体内促氧化剂和抗氧化剂状态失衡而导致氧化损伤。肾上腺类固醇应激激素在与这些应激源相关的氧化损伤中的作用尚未得到广泛研究。因此，本研究旨在通过比较在无其他施加应激源的情况下，低、中、高剂量外源性给予皮质酮对抗氧化防御系统的广泛关键成分的影响，来探究糖皮质激素在诱导氧化过程中的任何直接作用。此处呈现的数据表明，皮质酮的作用导致抗氧化防御大幅下降，这表现为自由基清除酶超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽S - 转移酶（GST）和谷胱甘肽还原酶（GR）在脑、肝和心脏中的活性协同下降，以及非酶抗氧化剂谷胱甘肽（GSH）和血清尿酸下降。此外，氧化应激标志物脂质过氧化和蛋白质羰基含量在脑、肝和心脏中显著增加。体内抗氧化状态受损与束缚应激的有害影响惊人地相似，表明应激激素在生理或心理应激期间对氧化损伤诱导有直接作用。在高剂量（40mg/kg）和低剂量（10mg/kg）皮质酮之间观察到SOD和CAT的剂量依赖性下降以及蛋白质氧化增加。这些发现对于氧化应激作为慢性应激适应不良的主要病理机制具有重要意义。因此，该研究表明应激激素在影响适应性反应期间诱导的氧化过程中具有因果作用。这可能对以细胞抗氧化剂为靶点的药物干预具有重要意义，这是一种在由生理或心理应激引起的各种精神和非精神疾病中预防氧化损伤的有前景的策略。
