Doxorubicin administration in rats significantly reduced left ventricular ejection fraction at 3 days (80.4% vs 89.6%, p=0.03) and induced early oxidative stress and autophagy dysregulation.
Does doxorubicin induce acute cardiotoxicity through oxidative stress, autophagy, and inflammation in a rat model?
Doxorubicin induces acute cardiotoxicity in rats characterized by early echocardiographic and electrocardiographic changes, driven by oxidative stress, dysregulated autophagy, and inflammation.
Absolute Event Rate: 80.4% vs 89.6%
p-value: p=0.03
Drug-induced cardiotoxicity is a life-threatening side effect of doxorubicin (DOX) treatment that impacts patient prognosis and survival. In the majority of cases, the acute clinical form often remains asymptomatic, with few patients presenting rather nonspecific electrocardiographic abnormalities. While chronic toxicity has been more widely studied, the alterations appearing in acute cardiotoxicity are much less investigated. Thus, our in vivo study aimed to evaluate the process of DOX-induced acute myocardial toxicity by investigating oxidative stress and autophagy markers as mechanisms of myocardial toxicity in correlation with echocardiography and electrocardiography findings. Our results show that both autophagy and oxidative homeostasis were disrupted as soon as 7 days after DOX treatment, alterations that occurred even before the significant increase of NT-proBNP, a clinical marker for cardiac suffering. Moreover, we found a large number of alterations in the electrocardiography and echocardiography of treated rats. These findings suggest that DOX-induced myocardial toxicity started early after treatment initiation, possibly marking the initial phase of the unfolding process of cardiac damage. Further studies are required to completely decipher the mechanisms of DOX-induced cardiotoxicity.
Dulf et al. (Mon,) conducted a other in Doxorubicin-induced acute cardiotoxicity (n=30). Doxorubicin vs. 5 mg/kg saline solution single intraperitoneal injection was evaluated on Left ventricular ejection fraction at 3 days (p=0.03). Doxorubicin administration in rats significantly reduced left ventricular ejection fraction at 3 days (80.4% vs 89.6%, p=0.03) and induced early oxidative stress and autophagy dysregulation.