Carvedilol treatment ameliorates acute coxsackievirus B3-induced myocarditis associated with oxidative stress reduction.

Abstract

Oxidative stress has been implicated in the pathogenesis of acute myocarditis. The imbalance between the occurrence of reactive oxygen species and the cellular antioxidant defense mechanism plays a key role in myocardial injury of viral myocarditis. Carvedilol, a nonselective beta-adrenoceptor antagonist with additional alpha1-adrenergic blocking and antioxidant properties, has been shown to be cardioprotective in experimental myocarditis. However, the expression of 4-hydroxy-2-nonenal (4-HNE), the most reliable marker of lipid peroxidation, has not been studied, and the antioxidative effects of carvedilol have not been investigated in the setting of acute viral myocarditis. This study was therefore designed to determine whether levels of lipid peroxides are elevated in the myocardium and whether carvedilol reduces the lipid peroxidation level and increases antioxidant enzyme activities. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of carvedilol and metoprolol on 14-day survival rate, myocardial histopathological changes, cardiac function, the expression of 4-HNE, virus titers, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidases (GSH-Px) activities were studied. Lipid peroxidations including 4-HNE and MDA, were elevated in murine coxsackievirus-induced acute viral myocarditis. Carvedilol, but not metoprolol, improved survival, reduced lipid peroxidations including 4-HNE and MDA, and increased antioxidant enzyme activities including SOD and GSH-Px with amelioration of acute viral myocarditis. These results show that carvedilol but not metoprolol exerts some of its beneficial effects by inhibiting peroxidants.

• Authors: Yue-Chun Li, Li-Sha Ge, Peng-Lin Yang, Ji-Fei Tang, Jia-Feng Lin, Peng Chen, Xue-qiang Guan
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 640 Issue 1-3 Pg. 112-6 (Aug 25 2010) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 20457150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 Elsevier B.V. All rights reserved.

Chemical References

• Adrenergic Antagonists
• Aldehydes
• Carbazoles
• Propanolamines
• Carvedilol
• Malondialdehyde
• Glutathione Peroxidase
• Superoxide Dismutase
• Metoprolol
• 4-hydroxy-2-nonenal

Topics

• Adrenergic Antagonists (pharmacology, therapeutic use)
• Aldehydes (metabolism)
• Animals
• Body Weight (drug effects)
• Carbazoles (pharmacology, therapeutic use)
• Carvedilol
• Electrocardiography
• Enterovirus (physiology)
• Glutathione Peroxidase (metabolism)
• Heart (drug effects, physiopathology)
• Hemodynamics (drug effects)
• Male
• Malondialdehyde (metabolism)
• Metoprolol (pharmacology)
• Mice
• Mice, Inbred BALB C
• Myocarditis (drug therapy, metabolism, pathology, virology)
• Myocardium (metabolism, pathology)
• Organ Size (drug effects)
• Oxidative Stress (drug effects)
• Propanolamines (pharmacology, therapeutic use)
• Superoxide Dismutase (metabolism)
• Survival Rate
• Time Factors
• Viral Load (drug effects)