Effects of polyethylene glycol conjugated superoxide dismutase on coxsackievirus B3 myocarditis in mice.
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.
Hiraoka
Y
Y
Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Kishimoto
C
C
Kurokawa
M
M
Ochiai
H
H
Sasayama
S
S
D000818:Animals; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D029822:Enterovirus B, Human; D016166:Free Radical Scavengers; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009205:Myocarditis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000627:therapeutic use*
D016166:Free Radical Scavengers; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase