Doxorubicin belongs to the class of
anthracycline antibiotics that is widely used in the treatment protocols of a wide range of
malignancies. The major deleterious effect of
doxorubicin use is the possible occurrence of
cardiotoxicity. This study aimed to delineate the possible effects of targeting oxidative stress, NLRP3
inflammasome, and autophagy by
fraxetin on
doxorubicin-induced cardiac dysfunction in rats. In a model of
doxorubicin-induced
cardiotoxicity, the effects of different doses of
fraxetin were assessed by determination of biochemical, histopathological, immunohistochemical, and electron microscopic changes.
Fraxetin, in a dose-dependent manner, was found to have the ability to mitigate the harmful effects of oxidative stress and
inflammation on myocardial muscles with significant decrease in NLRP3
inflammasome, augmentation of autophagy, and amelioration of the apoptotic signaling pathways. In addition,
fraxetin, in a dose-dependent manner, had the ability to combat the echocardiographic, histopathological, immunohistochemical, and electron microscopic changes induced by
doxorubicin in cardiomyocytes. As a result,
fraxetin may be put into consideration as a new adjuvant line of
therapy on the way to mitigate
doxorubicin-induced
cardiotoxicity.