Reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide are produced highly in
myocarditis. ROS, which not only act as effectors for pathogen killing but also mediate signal transduction in the
stress responsive pathways, are closely related with both innate and adaptive immunity. On the other hand, oxidative
stress overwhelming the capacity of anti-oxidative system generated in severe inflammation has been suggested
to damage tissues and exacerbate inflammation. Oxidative stress worsens the autoimmunological process of
myocarditis, and suppression of the anti-oxidative system and long-lasting oxidative stress could be one of the
pathological mechanisms of cardiac remodeling leading to inflammatory cardiomyopathy. Oxidative stress is considered
to be one of the promising treatment targets of myocarditis.
Evidences of anti-oxidative treatments in myocarditis have not been fully established. Basic strategies of anti-oxidative treatments include
inhibition of ROS production, activation of anti-oxidative enzymes and elimination of generated free radicals. ROS are produced
by mitochondrial respiratory chain reactions and enzymes including NADPH oxidases, cyclooxygenase, and xanthine oxidase. Other systems
involved in inflammation and stress response, such as NF-κB, Nrf2/Keap1, and neurohumoral factors also influence oxidative stress
in myocarditis. The efficacy of anti-oxidative treatments could also depend on the etiology and the phases of myocarditis. We review in
this article the pathological significance of ROS and oxidative stress, and the potential anti-oxidative treatments in myocarditis.