In vitro and in vivo study on the antioxidant activity of dexrazoxane

ObjectivesThe iron chelator dexrazoxane has been shown to significantly reduce anthracycline-induced cardiac toxicity in several randomized controlled studies. Aim of the present study was to assess the in vitro and in vivo antioxidant effects of dexrazoxane.MethodsThe in vitro antioxidant activity of dexrazoxane as its total oxyradical scavenging capacity (TOSC) was assessed and compared to that of some classic antioxidants such as reduced glutathione (GSH), uric acid and trolox. The plasma antioxidant activity of 20 newly-diagnosed non-Hodgkin lymphoma (NHL) patients scheduled to receive anthracycline-containing chemotherapy (ProMECE-CytaBOM) was also evaluated. Results were expressed as TOSC units.ResultsDexrazoxane exhibited an in vitro scavenging capacity towards hydroxyl radicals 320% higher than that of GSH (p < 0.00001), 20% higher than that of uric acid (p < 0.001), and 100% higher than that of trolox (p < 0.001). In the clinical study, ProMECE-CytaBOM infusion significantly reduced plasma TOSC in NHL patients (p = 0.0001). Dexrazoxane supplementation was able to restore plasma antioxidant activity in two hours from the end of the ProMECE-CytaBOM infusion.ConclusionsDexrazoxane has in vitro antioxidant capacity. In vivo, it is able to reduce the epirubicin-induced free radical production. The intrinsic antioxidant effect of this compound could explain the reduction of the anthracyclines-induced toxicity in those patients treated with dexrazoxane supplementation.