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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

Scavenging effects of dexrazoxane on hydroxyl free radicals generated from Fenton reaction. The inset shows the ESR spectrum of DMPO-OH. Details of the procedure are described in the “Materials and Methods” (n = 6).
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Figure 4: Scavenging effects of dexrazoxane on hydroxyl free radicals generated from Fenton reaction. The inset shows the ESR spectrum of DMPO-OH. Details of the procedure are described in the “Materials and Methods” (n = 6).

Mentions: To compare the scavenging effects of dexrazoxane in the absence and presence of iron, we next examined the effect of dexrazoxane on hydroxyl free radicals generated from Fenton reaction using ESR spectroscopy. As shown in Fig. 4, dexrazoxane can effectively scavenge hydroxyl radical generated from Fenton reaction and the IC50 is about 1.60 mg/mL. It seams from the result that dexrazoxane is more effective for scavenging hydroxyl radicals which are generated in the presence of iron, but it is hard to keep the hydroxyl radical concentration is the same in the two different generation system, even the same concentration of H2O2 was used.


Scavenging effects of dexrazoxane on free radicals.

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

Scavenging effects of dexrazoxane on hydroxyl free radicals generated from Fenton reaction. The inset shows the ESR spectrum of DMPO-OH. Details of the procedure are described in the “Materials and Methods” (n = 6).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Scavenging effects of dexrazoxane on hydroxyl free radicals generated from Fenton reaction. The inset shows the ESR spectrum of DMPO-OH. Details of the procedure are described in the “Materials and Methods” (n = 6).
Mentions: To compare the scavenging effects of dexrazoxane in the absence and presence of iron, we next examined the effect of dexrazoxane on hydroxyl free radicals generated from Fenton reaction using ESR spectroscopy. As shown in Fig. 4, dexrazoxane can effectively scavenge hydroxyl radical generated from Fenton reaction and the IC50 is about 1.60 mg/mL. It seams from the result that dexrazoxane is more effective for scavenging hydroxyl radicals which are generated in the presence of iron, but it is hard to keep the hydroxyl radical concentration is the same in the two different generation system, even the same concentration of H2O2 was used.

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