Norepinephrine administration in rats significantly increased GPx, GR, and SOD activity, decreased the GSH/GSSG ratio, and increased MDA levels, indicating oxidative damage.
Norepinephrine administration in rats induces oxidative damage and apoptosis through reactive intermediates from auto-oxidation, contributing to catecholamine-induced cardiotoxicity.
BACKGROUND: To investigate the cardiotoxic role of reactive oxygen species (ROS) and of products derived from catecholamines auto-oxidation, we studied: (1) the response of antioxidant cardiac cellular defence systems to oxidative stress induced by norepinephrine (NE) administration, (2) the effect of NE administration on cardiac beta1-adrenergic receptors by means of receptor binding assay, (3) the cellular morphological alterations related to the biologically cross-talk between the NE administration and cytokines tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), interleukins IL6, IL8, IL10. METHODS AND RESULTS: A total of 195 male rats was used in the experiment. All animals underwent electrocardiogram (EKG) before being sacrificed. The results obtained show that NE administration influences the antioxidant cellular defence system significantly increasing glutathione peroxidase (GPx) activity, glutathione reductase (GR) and superoxide dismutase (SOD). The oxidized glutathione (GSH/GSSG) ratio significantly decreases and malondialdehyde (MDA) levels increase showing a state of lipoperoxidation of cardiac tissue. We describe a significant apoptotic process randomly sparse in the damaged myocardium and the effect of ROS on the NE-mediated TNF-alpha, MCP-1, and IL6, IL8, IL10 production. CONCLUSIONS: Our results support the hypothesis that catecholamines may induce oxidative damage through reactive intermediates resulting from their auto-oxidation, irrespective of their interaction with adrenergic receptors, thus representing an important factor in the pathogenesis of catecholamines-induced cardiotoxicity. The rise of the cardioinhibitory cytokines may be interpreted as the adaptive response of jeopardized myocardium with respect to the cardiac dysfunction resulting from NE injection.
Neri et al. (Mon,) conducted a other in Catecholamine-induced cardiotoxicity (n=195). Norepinephrine administration was evaluated on Antioxidant cardiac cellular defence systems, cardiac beta1-adrenergic receptors, and cellular morphological alterations. Norepinephrine administration in rats significantly increased GPx, GR, and SOD activity, decreased the GSH/GSSG ratio, and increased MDA levels, indicating oxidative damage.