Correlation between cardiac oxidative stress and myocardial pathology due to acute and chronic norepinephrine administration in rats

Abstract

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 β1-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-α), 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-α, 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.

Endogenous sulfur dioxide protects against isoproterenol-induced myocardial injury and increases myocardial antioxidant capacity in rats

“…1,34 Meszaros et al 35 showed that administration of supramaximal dosages of ISO increased enddiastolic volume and end-diastolic pressure, contributing to ventricular dysfunctions, which possibly resulted from the auto-oxidation of catecholamines that stimulated oxidative stress via reactive mediators, leading to cardiotoxicity. 36 More interestingly, the ventricular dysfunction, as mentioned above, could be significantly prevented by antioxidants. 35,37 An increasing body of evidence suggests that free radicals, including reactive oxygen species and reactive nitrogen species, have long been recognized to act as the major mediators of cardiac injury, and antioxidants and free radical scavengers have been shown to minimize cardiac injury, which, to some extent, verifies that oxygen radicals have a key role in cardiac injury.…”

Unintended Consequences: Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia

“…The mechanism underlying this phenomena is unclear but a number of potential contributing mechanisms have been proposed including mitochondrial oxidative stress, microvascular thrombi and increased sarcolemma membrane permeability 36,37 . Catecholamines have been shown to increase myocardial oxidative stress in experimental models, 38 and in a murine model of sepsis Haileselassie et al demonstrated that increased oxidative stress was a central factor in development of septic induced myocardial dysfunction. The observed increase in troponin is a concerning find as it suggests the increased vasopressor requirement is not a benign epiphenomena and may produce secondary cardiac injury.…”

The protective effect of picroside II against hypoxia/reoxygenation injury in neonatal rat cardiomyocytes

“…However, GPx requires GSH to perform this function. GSH has a direct antioxidant function by reacting with superoxide radicals to produce GSSG (Neri et al, 2007;Franco & Cidlowski, 2009). In addition, the level of MDA reflects the extent of cell injury by oxidative stress.…”