Limits...
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.

Show MeSH

Related in: MedlinePlus

Immunohistochemical detection of TNFα with positive reaction after treatment: control (A), 4 hrs after treatment (B), 8 hrs after treatment (C), 24 hrs after treatment (D).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4401229&req=5

fig06: Immunohistochemical detection of TNFα with positive reaction after treatment: control (A), 4 hrs after treatment (B), 8 hrs after treatment (C), 24 hrs after treatment (D).

Mentions: The immunohistochemical study revealed an intensive positive result to TUNEL assay (Fig. 5A–D): approximately 3 ± 1, 3 ± 2, 12 ± 8, 38 ± 18, 45 ± 17, 60 ± 18 and 70 ± 13% apoptotic cells were observed after 1, 4, 8, 24, 48 hrs, 10 and 30 days (Table 2). TNF-α was demonstrated to significantly increase in heart specimens 4 hrs after NE infusion with the strongest evidence from the eighth hour to the 48th hour. On the 10th day, TNF-α significantly decreased in treated rats (Fig. 6A–D). MCP-1 demonstrated a gradually strong positive reaction from the first hour until 24th hour, to decrease until normalization after 48 hrs (Fig. 7A, B, C and D). IL8 was rapidly positive with a peak of evidence on eighth hour to decrease on 24th hour. On the 48th hour, both IL6 and IL10 demonstrated the strongest evidence but they differed among one another with respect to a gradual decrease for IL6 on 10th day when IL10 was strongly positive until 30 days (Table 3) (Fig. 8A–D).


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)

Immunohistochemical detection of TNFα with positive reaction after treatment: control (A), 4 hrs after treatment (B), 8 hrs after treatment (C), 24 hrs after treatment (D).
© Copyright Policy
Related In: Results  -  Collection

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

fig06: Immunohistochemical detection of TNFα with positive reaction after treatment: control (A), 4 hrs after treatment (B), 8 hrs after treatment (C), 24 hrs after treatment (D).
Mentions: The immunohistochemical study revealed an intensive positive result to TUNEL assay (Fig. 5A–D): approximately 3 ± 1, 3 ± 2, 12 ± 8, 38 ± 18, 45 ± 17, 60 ± 18 and 70 ± 13% apoptotic cells were observed after 1, 4, 8, 24, 48 hrs, 10 and 30 days (Table 2). TNF-α was demonstrated to significantly increase in heart specimens 4 hrs after NE infusion with the strongest evidence from the eighth hour to the 48th hour. On the 10th day, TNF-α significantly decreased in treated rats (Fig. 6A–D). MCP-1 demonstrated a gradually strong positive reaction from the first hour until 24th hour, to decrease until normalization after 48 hrs (Fig. 7A, B, C and D). IL8 was rapidly positive with a peak of evidence on eighth hour to decrease on 24th hour. On the 48th hour, both IL6 and IL10 demonstrated the strongest evidence but they differed among one another with respect to a gradual decrease for IL6 on 10th day when IL10 was strongly positive until 30 days (Table 3) (Fig. 8A–D).

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