The
oxygen free radical system has been reported to be activated by influenza virus
infection in the lungs. However, the involvement of
oxygen radicals in viral
myocarditis is still unknown.
Captopril, an
angiotensin-converting enzyme (
ACE) inhibitor and potent
free radical scavenger with a sulfhydryl group, was effective for the treatment of viral
myocarditis, while
enalapril, an
ACE inhibitor without a sulfhydryl group, was not effective against acute
myocarditis. In this study, we investigated the role of
oxygen radicals in the pathogenesis of viral
myocarditis and the
therapeutic effects of agents with a sulfhydryl group. 4-wk-old BALB/c mice were inoculated with the encephalomyocarditis virus, and treated with
captopril or N,2-mercapto-propionyl
glycine (MPG), a sulfhydryl-containing
amino acid derivative without ACE inhibiting property, from days 4 to 14. On day 14,
captopril and MPG significantly improved survival of mice and myocardial injury (
necrosis, cellular infiltration, and calcification) in a dose-dependent manner compared with the infected control group. Thus,
captopril and MPG were effective for the treatment of virus-induced
myocarditis. Furthermore, a striking induction of
manganese superoxide dismutase (
Mn-SOD) and
copper/
zinc SOD (Cu/Zn-SOD) mRNAs in infected hearts was found (8-13-fold for
Mn-SOD and 4-11-fold for Cu/Zn-SOD) when compared with age-matched uninfected mice hearts. MPG completely inhibited the increase of both mRNAs, even when treatment was started on day 4. Thus,
oxygen radicals may play an important role in the pathogenesis of viral
myocarditis, and a therapeutic approach by eliminating
oxygen radicals seems possible.