Scavenging Effects of Dexrazoxane on Free Radicals

Abstract

Dexrazoxane (ICRF-187) has been clinically used to reduce doxorubicin-induced cardiotoxicity for more than 20 years. It has been proposed that dexrazoxane may act through its rings-opened hydrolysis product ADR-925, which can either remove iron from the iron-doxorubicin complex or bind to free iron, thus preventing iron-based oxygen radical formation. However, it is not known whether the antioxidant actions of dexrazoxane are totally dependent on its metabolization to its rings-opened hydrolysis product and whether dexrazoxane has any effect on the iron-independent oxygen free radical production. In this study, we examined the scavenging effect of dexrazoxane on hydroxyl, superoxide, lipid, DPPH and ABTS⁺ free radicals in vitro solution systems. The results demonstrated that dexrazoxane was an antioxidant that could effectively scavenge these free radicals and the scavenging effects of dexrazoxane did not require the enzymatic hydrolysis. In addition, dexrazoxane was capable to inhibit the generation superoxide and hydroxyl radicals in iron free reaction system, indicating that the antioxidant properties of dexrazoxane were not solely dependent on iron chelation. Thus the application of dexrazoxane should not be limited to doxorubicin-induced cardiotoxicity. Instead, as an effective antioxidant that has been clinically proven safe, dexrazoxane may be used in a broader spectrum of diseases that are known to be benefited by antioxidant treatments.