Collateral Damage in Cancer Chemotherapy: Oxidative Stress in Nontargeted Tissues

DOX-induced generation of ROS/RNS in heart. Cleavage of the sugar residue and reduction of the carbonyl group at C13 produce DOX aglycone and doxorubicinol (DOXol), respectively. Redox cycling of DOX and its metabolites generates ROS including O₂^·− and H₂O₂. ROS and DOXol can affect iron metabolism and lead to increased levels of cellular free iron ions, which induce further ROS/RNS generation.