Lipid peroxidation and antioxidant enzymes in isoproterenol induced oxidative stress in rat tissues

The oxidative metabolism of catecholamines produce quinones which react with oxygen to produce superoxide anions (O-2(-.)) 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 O-2(-.). However, increased amounts of O-2(-.), inhibited SOD activity at 3 acid 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. (C) 1998 The Italian Pharmacological Society.