title: In vitro and in vivo study on the antioxidant activity of dexrazoxane.
abstract: 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.
authors.affiliation: Department of Internal Medicine, University of Pisa, Via Roma, 67, 56126 Pisa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Galetta
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Franzoni
authors.forename: Giulia
authors.initials: G
authors.lastname: Cervetti
authors.forename: Francesco
authors.initials: F
authors.lastname: Regoli
authors.forename: Poupak
authors.initials: P
authors.lastname: Fallahi
authors.forename: Leonardo
authors.initials: L
authors.lastname: Tocchini
authors.forename: Angelo
authors.initials: A
authors.lastname: Carpi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Antonelli
authors.forename: Mario
authors.initials: M
authors.lastname: Petrini
authors.forename: Gino
authors.initials: G
authors.lastname: Santoro
mesh_terms: 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
chemical_list: 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