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


METHODS
The 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.


RESULTS
Dexrazoxane 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.


CONCLUSIONS
Dexrazoxane 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.
Galetta
Fabio
F
Department of Internal Medicine, University of Pisa, Via Roma, 67, 56126 Pisa, Italy.
Franzoni
Ferdinando
F
Cervetti
Giulia
G
Regoli
Francesco
F
Fallahi
Poupak
P
Tocchini
Leonardo
L
Carpi
Angelo
A
Antonelli
Alessandro
A
Petrini
Mario
M
Santoro
Gino
G
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology*; D001761:Bleomycin / Q000009:adverse effects / Q000627:therapeutic use; D002839:Chromans / Q000494:pharmacology; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D003561:Cytarabine / Q000009:adverse effects / Q000627:therapeutic use; D015251:Epirubicin / Q000009:adverse effects / Q000627:therapeutic use; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011929:Razoxane / Q000494:pharmacology*; D013997:Time Factors; D014527:Uric Acid / Q000494:pharmacology; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
D000975:Antioxidants; D002839:Chromans; D016166:Free Radical Scavengers; D003561:Cytarabine; D001761:Bleomycin; D014527:Uric Acid; D015251:Epirubicin; D011929:Razoxane; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D005978:Glutathione; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D011241:Prednisone; D008727:Methotrexate