Doxorubicin-induced markers of myocardial autophagic signaling in sedentary and exercise trained animals

Doxorubicin (DOX) is an effective antitumor agent used in cancer treatment. However, its clinical use is limited due to cardiotoxicity. Indeed, the side effects of DOX are irreversible and include the development of cardiomyopathy and ultimately congestive heart failure. Although many studies have investigated the events leading to DOX-induced cardiotoxicity, the mechanisms responsible for DOX-induced cardiotoxicity remain unknown. In general, evidence suggests that DOX-induced cardiotoxicity is associated with an increased generation of reactive oxygen species and oxidative damage, leading to the activation of cellular proteolytic systems. In this regard, the autophagy/lysosomal proteolytic system is a constitutively active catabolic process that is responsible for the degradation of both organelles and cytosolic proteins. We tested the hypothesis that systemic DOX administration results in altered cardiac gene and protein expression of mediators of the autophagy/lysosomal system. Our results support thi...