Thioredoxin, a redox-regulating protein, is expressed in spontaneous myocarditis in inbred strains of mice

Redox-regulating mechanisms may be involved in the pathogenesis of aging. Thioredoxin (TRX) is a small multifunctional protein which contains a redox active sequence. Spontaneous myocarditis is often observed in aged mice. In this study, we examined the histopathology and characteristics of TRX expression in spontaneous myocarditis in inbred strains of mice. No spontaneous myocarditis was found in adult 4-week-old inbred strains of mice. High incidence of spontaneous myocarditis was found in aged 8-week-old DBA/2 mice, and low incidence was in 8-week-old BALB/c or C57BL/6 mice. The lesions, limited to the right ventricle, were most severe in DBA/2 mice. TRX was upregulated, and the expression was correlated with the severity of the disease in these strains. Also, 8-hydroxy-2'-deoxyguanosine (8-OHdG), which was an established marker for oxidative stress, was concomitantly positive in necrotic lesions among them. In addition, the long-term anti-oxidant treatment with N-acetylcysteine (NAC) suppressed the development of spontaneous myocarditis. Thus, TRX may be induced by the spontaneously developed myocarditis, and the redox-regulating system may play an important role in the development of aging-related myocarditis. (C) 2003 Published by Elsevier Ireland Ltd.