Fig. 1.

DOX-related redox cycling. The mitochondrial NADH-dependent enzymes can convert quinone moiety in ring C of DOX into semiquinone form through single-electron reduction. The semiquinone form of DOX reacts with O₂ to form ${\text{O}}_2^{·-}$, which is neutralized by SOD to H₂O₂. In the presence of Fe²⁺, H₂O₂ might also generate highly reactive and toxic OH∙, which reacts with DNA, proteins and lipids, leading to DNA damage and lipid peroxidation. DOX doxorubicin, NADH nicotinamide adenine dinucleotide hydrate, O₂ oxygen molecule, ${\text{O}}_2^{·-}$ superoxide anion, SOD superoxide dismutase, H₂O₂ hydrogen peroxide, Fe²⁺ iron, OH∙, hydroxyl radical, CAT catalase, GPx glutathione-dependent peroxidase, H₂O water