ROLE OF OXYGEN-DERIVED FREE-RADICALS IN THE PATHOGENESIS OF COXSACKIEVIRUS-B3 MYOCARDITIS IN MICE

Objective: The aim was to test the role of oxygen derived free radicals in the development of myocarditis. This involved investigating the effects of polyethylene glycol conjugated superoxide dismutase (PEG-SOD, an enzyme catalysing the conversion of O2.- to H2O2) and polyethylene glycol conjugated catalase (PEG-catalase, accelerating the reaction of H2O2 to H2O and O2) 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) U.kg-1.d-1, and PEG-SOD, 1 X 10(3) U.kg-1.d-1, plus PEG-catalase, 1 x 10(3) U.kg-1-d-1, were injected subcutaneously daily on days 0 to 14. Treated groups were compared to the infected control. Results: On day 7, there were no significant differences in pathological scores among the three groups. On day 14, the cellular infiltration, myocardial necrosis, and calcification scores were significantly lower in the PEG-SOD group and the PEG-SOD plus PEG-catalase group than in the control. There were no significant differences in pathological scores between the PEG-SOD group and the PEG-SOD plus PEG-catalase group. There were no differences in the myocardial virus titres on day 7 among the three groups. On day 14, virus was not detected from the myocardium in any of the three groups. Conclusions: The results suggest that superoxide anion is mostly responsible for myocyte injury in CB3 myocarditis in mice, and that hydrogen peroxide formed as a result of dismutation of superoxide anion may not play a significant role in the development of myocarditis. Superoxide anion is one of the most important factors in free radical mediated injury in CB3 myocarditis in mice and the administration of PEG-SOD alone has therapeutic potential in clinical CB3 myocarditis.