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Scavenging effects of dexrazoxane on free radicals.

Junjing Z, Yan Z, Baolu Z - J Clin Biochem Nutr (2010)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Academia Sinica, Bejing 100101, China.

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.

No MeSH data available.


Related in: MedlinePlus

a. A reaction scheme for the hydrolysis of dexrazoxane to metabolites B and C and its strong metal ion-chelating form ADR-925; b. DHOase-catalyzed reversible conversion of L-dihydroorotate into N-carbamoyl-L-aspartate (carbamyl aspartate).
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Figure 1: a. A reaction scheme for the hydrolysis of dexrazoxane to metabolites B and C and its strong metal ion-chelating form ADR-925; b. DHOase-catalyzed reversible conversion of L-dihydroorotate into N-carbamoyl-L-aspartate (carbamyl aspartate).

Mentions: Dexrazoxane (ICRF-187; Fig. 1) has been clinically used to reduce doxorubicin-induced cardiotoxicity for more than 20 years [1–8]. Evidence has indicated that the iron-dependent oxygen free radical formation on the relatively unprotected cardiac muscle is a major cause of the cadiotoxicity induced by doxorubicin [9, 10]. It has been proposed that dexrazoxane can be converted by dihydroorotase (DHOase) to its rings-opened hydrolysis product ADR-925 (Fig. 1), which can either remove iron from the iron-doxorubicin complex or bind to free iron, thus preventing iron-based oxygen radical formation [11–16]. However, several questions remain unanswered. First, are the antioxidant actions of dexrazoxane totally dependent on its metabolization to its rings-opened hydrolysis product ADR-925? Second, does dexrazoxane have any effect on the iron-independent oxygen free radical production or it only scavenges oxygen free radical generated from iron-dependent process? Elucidation of these questions may help to evaluate the clinical use of dexrazoxane as an antioxidant directly in conditions other than doxorubicin-induced cardiotoxicity.


Scavenging effects of dexrazoxane on free radicals.

Junjing Z, Yan Z, Baolu Z - J Clin Biochem Nutr (2010)

a. A reaction scheme for the hydrolysis of dexrazoxane to metabolites B and C and its strong metal ion-chelating form ADR-925; b. DHOase-catalyzed reversible conversion of L-dihydroorotate into N-carbamoyl-L-aspartate (carbamyl aspartate).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2966934&req=5

Figure 1: a. A reaction scheme for the hydrolysis of dexrazoxane to metabolites B and C and its strong metal ion-chelating form ADR-925; b. DHOase-catalyzed reversible conversion of L-dihydroorotate into N-carbamoyl-L-aspartate (carbamyl aspartate).
Mentions: Dexrazoxane (ICRF-187; Fig. 1) has been clinically used to reduce doxorubicin-induced cardiotoxicity for more than 20 years [1–8]. Evidence has indicated that the iron-dependent oxygen free radical formation on the relatively unprotected cardiac muscle is a major cause of the cadiotoxicity induced by doxorubicin [9, 10]. It has been proposed that dexrazoxane can be converted by dihydroorotase (DHOase) to its rings-opened hydrolysis product ADR-925 (Fig. 1), which can either remove iron from the iron-doxorubicin complex or bind to free iron, thus preventing iron-based oxygen radical formation [11–16]. However, several questions remain unanswered. First, are the antioxidant actions of dexrazoxane totally dependent on its metabolization to its rings-opened hydrolysis product ADR-925? Second, does dexrazoxane have any effect on the iron-independent oxygen free radical production or it only scavenges oxygen free radical generated from iron-dependent process? Elucidation of these questions may help to evaluate the clinical use of dexrazoxane as an antioxidant directly in conditions other than doxorubicin-induced cardiotoxicity.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Academia Sinica, Bejing 100101, China.

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.

No MeSH data available.


Related in: MedlinePlus