Rathore N, John S, Kale M, Bhatnagar D
School of Biochemistry, D.A. University, Khandwa Road, Indore, India.
Pharmacol Res. 1998 Oct;38(4):297-303. doi: 10.1006/phrs.1998.0365.
The oxidative metabolism of catecholamines produce quinones which react with oxygen to produce superoxide anions (O2-.) and H2O2. The catecholamines, however, are important under stress conditions but may have damaging effects due to the generation of reactive oxygen species (ROS) and formation of oxidation products. ROS are involved as causative factors in many diseases, therefore, the generation of ROS by catecholamines may also contribute to this process. Isoproterenol (ISO) was administered to rats in two doses so as to evaluate their beta-adrenergic and toxicological actions in terms of lipid peroxidation (LPO) and the changes in the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST) and glutathione (GSH) content in heart, liver and kidney. ISO treatment caused LPO in tissues, however, the heart initially showed decreased LPO. This is attributed to the condition of hypertrophy by which the heart can protect itself to a limited extent against oxidative stress. The second dose of ISO, administered 24 h after the first treatment, showed toxic effects resulting in a higher increase in LPO. The increased SOD activity in tissues 3 days after a dose of ISO suggests that the ROS may induce SOD activity to dismutate O2-. However, increased amounts of O2-., inhibited SOD activity at 3 and 6 h with recovery towards control values at 12 h of a second dose of ISO treatment. CAT activity in tissues increased at 6 h of a second dose of ISO treatment. The elevated SOD and CAT enzymes in tissues indicate a response due to increased ROS. The increase in GSH content in the heart, liver and kidney at day 2 of ISO treatment and 12 h after the second dose of ISO may also neutralise oxidative stress. The inhibition in GST activity in tissues was observed probably due to increased ROS generation, however, GST activity partially recovered by 12 h after the second dose of ISO, in an attempt to counteract oxidative stress. The result shows that ISO induced oxidative stress and the increase of the antioxidant system in tissues may attenuate oxidative stress. It is suggested that ROS generation in the oxidation of catecholamines may be partially counteracted by the antioxidant system in tissues.
儿茶酚胺的氧化代谢会产生醌类物质，醌类与氧气反应生成超氧阴离子（O2-.）和过氧化氢。然而，儿茶酚胺在应激条件下很重要，但由于活性氧（ROS）的产生和氧化产物的形成，可能具有破坏作用。ROS是许多疾病的致病因素，因此，儿茶酚胺产生ROS也可能促成这一过程。以两种剂量给大鼠注射异丙肾上腺素（ISO），以便从脂质过氧化（LPO）以及心脏、肝脏和肾脏中抗氧化酶如超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽-S-转移酶（GST）和谷胱甘肽（GSH）含量的变化方面评估其β-肾上腺素能和毒理学作用。ISO处理导致组织中的LPO增加，然而，心脏最初显示LPO降低。这归因于肥大状态，通过这种状态心脏可以在一定程度上保护自身免受氧化应激。在首次处理后24小时给予的第二剂ISO显示出毒性作用，导致LPO升高幅度更大。一剂ISO处理3天后组织中SOD活性增加表明ROS可能诱导SOD活性使O2-发生歧化反应。然而，O2-.量的增加在第二剂ISO处理3小时和6小时时抑制了SOD活性，在12小时时恢复到对照值。第二剂ISO处理6小时时组织中的CAT活性增加。组织中SOD和CAT酶的升高表明是由于ROS增加引起的反应。ISO处理第2天以及第二剂ISO处理12小时后心脏、肝脏和肾脏中GSH含量的增加也可能中和氧化应激。组织中GST活性受到抑制可能是由于ROS生成增加，然而，第二剂ISO处理12小时后GST活性部分恢复，试图抵消氧化应激。结果表明ISO诱导氧化应激，组织中抗氧化系统的增加可能减轻氧化应激。提示儿茶酚胺氧化过程中ROS的产生可能被组织中的抗氧化系统部分抵消。
