In addition, cardiac iron-overload, which is mediated by the enhanced expression of transferrin, an iron transferring glycoprotein, further accelerates Dox-induced oxidative stress by suppressing the activity of endogenous antioxidants [catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidases (GPXs)] which, consequently causes the peroxidation and rupture of membrane lipids and resultant ferroptosis (28). This evidence concerns the gene SOD1 and Tangier disease.