Enhanced expression of superoxide dismutase messenger RNA in viral myocarditis. An SH-dependent reduction of its expression and myocardial injury.
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.
Department of Molecular Diagnostics, Faculty of Medicine, Kyoto University, Japan.
H
H
Suzuki
A
A
Matsumori
Y
Y
Matoba
B S
BS
Kyu
A
A
Tanaka
J
J
Fujita
S
S
Sasayama
D000818:Animals; D001483:Base Sequence; D001835:Body Weight; D002216:Captopril / Q000494:pharmacology; D004686:Encephalomyocarditis virus; D004769:Enterovirus Infections / Q000201:enzymology*; D005609:Free Radicals / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009205:Myocarditis / Q000188:drug therapy / Q000201:enzymology*; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D010100:Oxygen / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D016019:Survival Analysis; D008625:Tiopronin / Q000494:pharmacology
D005609:Free Radicals; D012333:RNA, Messenger; D002216:Captopril; D008625:Tiopronin; D013482:Superoxide Dismutase; D010100:Oxygen