title: 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 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].
  
  
  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.
authors: Department of Forensic Pathology, University of Foggia, Italy.
authors: Margherita
authors: M
authors: Neri
authors: Daniela
authors: D
authors: Cerretani
authors: Anna Ida
authors: AI
authors: Fiaschi
authors: Pasini Franco
authors: PF
authors: Laghi
authors: Pietro Euea
authors: PE
authors: Lazzerini
authors: Angela Bruna
authors: AB
authors: Maffione
authors: Lucia
authors: L
authors: Micheli
authors: Giancarlo
authors: G
authors: Bruni
authors: Cristina
authors: C
authors: Nencini
authors: Giorgio
authors: G
authors: Giorgi
authors: Stefano
authors: S
authors: D'Errico
authors: Carmela
authors: C
authors: Fiore
authors: Cristoforo
authors: C
authors: Pomara
authors: Irene
authors: I
authors: Riezzo
authors: Emanuela
authors: E
authors: Turillazzi
authors: Vittorio
authors: V
authors: Fineschi
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004334:Drug Administration Schedule; D004562:Electrocardiography; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000187:drug effects; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D016207:Cytokines; D017382:Reactive Oxygen Species; D018342:Receptors, Adrenergic, beta-1; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D019803:Glutathione Disulfide; D009638:Norepinephrine