Iron-doxorubicin complex (Fe-DOX) (Fe-DOX)

The Iron-doxorubicin complex (Fe-DOX) is a coordination compound formed by the chelation of ferric iron (Fe3+) by the anthracycline antibiotic doxorubicin (Minotti et al., 1999). While doxorubicin is a potent chemotherapeutic that targets DNA and topoisomerase II, the formation of the Fe-DOX complex is widely recognized as a primary driver of its severe, dose-limiting cardiotoxicity (Xu et al., 2005). This complex is highly redox-active; it undergoes cycles of reduction and oxidation that catalyze the production of reactive oxygen species (ROS), particularly hydroxyl radicals, via Fenton-like reactions (Kaiserova et al., 2007). These radicals cause extensive lipid peroxidation of the mitochondrial membranes in cardiomyocytes, leading to cellular dysfunction and apoptosis (Simunek et al., 2009). Because the heart has lower levels of protective antioxidant enzymes compared to other organs, it is uniquely vulnerable to the oxidative stress generated by this complex (Link et al., 1996). Clinical management often involves the use of dexrazoxane, an iron-chelating agent that prevents the formation of the Fe-DOX complex or removes iron from existing complexes to mitigate cardiac damage (Hasinoff et al., 2003).

Other names

Ferric-doxorubicin complexFe(III)-doxorubicinIron-adriamycin complexFe-adriamycin

The complex acts as a redox catalyst that facilitates the formation of hydroxyl radicals from hydrogen peroxide via Fenton chemistry, leading to oxidative damage of lipids, proteins, and DNA within cardiomyocytes (Minotti et al., 1999; Xu et al., 2005).