Effects of polyethylene glycol conjugated superoxide dismutase on coxsackievirus B3 myocarditis in mice. 1992

Y Hiraoka, and C Kishimoto, and M Kurokawa, and H Ochiai, and S Sasayama
Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.

OBJECTIVE The aim was to examine the role of oxygen derived free radicals in the development of myocarditis by investigating the effects of polyethylene glycol conjugated superoxide dismutase (PEG-SOD), a potent scavenger of oxygen free radicals, upon coxsackievirus B3 (CB3) myocarditis. METHODS Two week old male C3H/He mice were inoculated intraperitoneally with 10(3) plaque forming units of CB3. PEG-SOD, 1 x 10(3), 5 x 10(3), 1 x 10(4), and 1 x 10(5) U.kg-1 x d-1, was given subcutaneously daily on days 0 to 14. Treated groups were compared to the infected control. RESULTS The survival rate of the 1 x 10(5) U.kg-1 x d-1 PEG-SOD group was lower than that of the infected control group (40% v 78%, p < 0.01). The survival rates of the other treated groups did not differ significantly from the infected control. The myocardial calcification score in the 1 x 10(5) U.kg-1 x d-1 PEG-SOD group was higher than in the infected control group on d 7, when myocardial virus titres did not differ significantly among the five groups. The scores for myocardial cellular infiltration and myocardial necrosis in the 1 x 10(3) and the 5 x 10(3) U.kg-1 x d-1 PEG-SOD groups were significantly lower than in the infected control on d 14, when myocardial viruses were not detected in the five groups. However, the myocardial necrosis and myocardial calcification scores in the 1 x 10(5) U.kg-1 x d-1 PEG-SOD group were higher than in the infected control. CONCLUSIONS The improvement of cardiac pathology in the 1 x 10(3) and the 5 x 10(3) U.kg-1 x d-1 PEG-SOD groups seems to have resulted not from the reduction in myocardial virus titres but from inhibition of generation of oxygen free radicals. The mechanism of the impaired survival and aggravation of cardiac pathology in the 1 x 10(5) U.kg-1 x d-1 PEG-SOD group is unknown. The results suggest that oxygen free radicals may be involved in the pathogenesis and development of CB3 myocarditis and that appropriate dosages of PEG-SOD have therapeutic potential for clinical CB3 myocarditis, although caution must be paid to the treatment window.

UI MeSH Term Description Entries
D008297 Male Males
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009205 Myocarditis Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies. Carditis,Myocarditides
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D011092 Polyethylene Glycols Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS. Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D003384 Coxsackievirus Infections A heterogeneous group of infections produced by coxsackieviruses, including HERPANGINA, aseptic meningitis (MENINGITIS, ASEPTIC), a common-cold-like syndrome, a non-paralytic poliomyelitis-like syndrome, epidemic pleurodynia (PLEURODYNIA, EPIDEMIC) and a serious MYOCARDITIS. Coxsackie Virus Infections,Infections, Coxsackie Virus,Infections, Coxsackievirus,Coxsackie Virus Infection,Coxsackievirus Infection
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013482 Superoxide Dismutase An oxidoreductase that catalyzes the reaction between SUPEROXIDES and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. Hemocuprein,Ag-Zn Superoxide Dismutase,Cobalt Superoxide Dismutase,Cu-Superoxide Dismutase,Erythrocuprein,Fe-Superoxide Dismutase,Fe-Zn Superoxide Dismutase,Iron Superoxide Dismutase,Manganese Superoxide Dismutase,Mn-SOD,Mn-Superoxide Dismutase,Ag Zn Superoxide Dismutase,Cu Superoxide Dismutase,Dismutase, Ag-Zn Superoxide,Dismutase, Cobalt Superoxide,Dismutase, Cu-Superoxide,Dismutase, Fe-Superoxide,Dismutase, Fe-Zn Superoxide,Dismutase, Iron Superoxide,Dismutase, Manganese Superoxide,Dismutase, Mn-Superoxide,Dismutase, Superoxide,Fe Superoxide Dismutase,Fe Zn Superoxide Dismutase,Mn SOD,Mn Superoxide Dismutase,Superoxide Dismutase, Ag-Zn,Superoxide Dismutase, Cobalt,Superoxide Dismutase, Fe-Zn,Superoxide Dismutase, Iron,Superoxide Dismutase, Manganese
D016166 Free Radical Scavengers Substances that eliminate free radicals. Among other effects, they protect PANCREATIC ISLETS against damage by CYTOKINES and prevent myocardial and pulmonary REPERFUSION INJURY. Free Radical Scavenger,Radical Scavenger, Free,Scavenger, Free Radical,Scavengers, Free Radical

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