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

Neri M, Cerretani D, Fiaschi AI, Laghi PF, Lazzerini PE, Maffione AB, Micheli L, Bruni G, Nencini C, Giorgi G, D'Errico S, Fiore C, Pomara C, Riezzo I, Turillazzi E, Fineschi V - J. Cell. Mol. Med. (2007 Jan-Feb)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Forensic Pathology, University of Foggia, Italy.

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 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.

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Related in: MedlinePlus

Confocal laser scanning microscope: foci of myocardial cells with ruptured myofibrils and characterized by hypereosinophilic bands of hypercontracted sarcomeres demonstrated by granular cytoplasm.
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fig04: Confocal laser scanning microscope: foci of myocardial cells with ruptured myofibrils and characterized by hypereosinophilic bands of hypercontracted sarcomeres demonstrated by granular cytoplasm.

Mentions: The only lesion found were scattered foci of contraction band necrosis (CBN), typical of norepinephrine necrosis (NN) [20].This lesion was already visible in rats sacrificed at 1 hr and consisted of foci of few hypercontracted myocardial cells, intensively stained by eosin. This first change was associated with foci of myocardial cells with ruptured myofibrils and characterized by hypereosinophilic bands of hypercontracted sarcomeres alternated by clear empty spaces (Fig. 4A–D). Subsequently, after 8 hrs, a scanty infiltrate of macrophagic monocytes around the necrotic myocardial cells was observed. Within 24 hrs this infiltrate became more widespread with an increased number of elements and an early removal of the necrotic material. When the latter was completely removed, the myocardial cell appeared as an empty sarcolemmal tubes that proved the presence of macrophages, resulting in an “alveolar pattern”. At 30 days we were unable to see a clearcut fibrous repair of the necrotic foci that maintained the previously described changes. The number of necrotic foci and myocardial cells × 100 mm2 of the histological area are reported in Table 2.


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

Neri M, Cerretani D, Fiaschi AI, Laghi PF, Lazzerini PE, Maffione AB, Micheli L, Bruni G, Nencini C, Giorgi G, D'Errico S, Fiore C, Pomara C, Riezzo I, Turillazzi E, Fineschi V - J. Cell. Mol. Med. (2007 Jan-Feb)

Confocal laser scanning microscope: foci of myocardial cells with ruptured myofibrils and characterized by hypereosinophilic bands of hypercontracted sarcomeres demonstrated by granular cytoplasm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401229&req=5

fig04: Confocal laser scanning microscope: foci of myocardial cells with ruptured myofibrils and characterized by hypereosinophilic bands of hypercontracted sarcomeres demonstrated by granular cytoplasm.
Mentions: The only lesion found were scattered foci of contraction band necrosis (CBN), typical of norepinephrine necrosis (NN) [20].This lesion was already visible in rats sacrificed at 1 hr and consisted of foci of few hypercontracted myocardial cells, intensively stained by eosin. This first change was associated with foci of myocardial cells with ruptured myofibrils and characterized by hypereosinophilic bands of hypercontracted sarcomeres alternated by clear empty spaces (Fig. 4A–D). Subsequently, after 8 hrs, a scanty infiltrate of macrophagic monocytes around the necrotic myocardial cells was observed. Within 24 hrs this infiltrate became more widespread with an increased number of elements and an early removal of the necrotic material. When the latter was completely removed, the myocardial cell appeared as an empty sarcolemmal tubes that proved the presence of macrophages, resulting in an “alveolar pattern”. At 30 days we were unable to see a clearcut fibrous repair of the necrotic foci that maintained the previously described changes. The number of necrotic foci and myocardial cells × 100 mm2 of the histological area are reported in Table 2.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Forensic Pathology, University of Foggia, Italy.

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 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.

Show MeSH
Related in: MedlinePlus