Dexrazoxane HCl

Dexrazoxane (10 mM), known clinically to limit anthracycline cardiac toxicity, prevents daunorubicin-induced myocyte apoptosis, but not necrosis induced by higher anthracycline concentrations in rat cardiac myocytes. ^[1] Dexrazoxane presumably exerts its cardioprotective effects by either binding free or loosely bound iron, or iron complexed to doxorubicin, thus preventing or reducing site-specific oxygen radical production that damages cellular components. ^[2] Dexrazoxane specifically abolishes the DNA damage signal gamma-H2AX induced by doxorubicin, but not camptothecin or hydrogen peroxide, in H9C2 cardiomyocytes. Dexrazoxane also induces rapid degradation of Top2beta, which paralleles the reduction of doxorubicin-induced DNA damage. Dexrazoxane antagonizes doxorubicin-induced DNA damage through its interference with Top2beta, which could implicate Top2beta in doxorubicin cardiotoxicity. ^[3] Dexrazoxane is hydrolyzed to its active form intracellularly and binds iron to prevent the formation of superhydroxide radicals, thus preventing mitochondrial destruction. ^[4]

Dexrazoxane combined with doxorubicin, daunorubicin, or idarubicin reduces the tissue lesions in B6D2F1 mice (expressed as area under the curve of wound size times duration) by 96%, 70%, and 87%, respectively. Dexrazoxane combined with doxorubicin, daunorubicin, or idarubicin results in a statistically significant reduction in the fraction of mice with wounds as well as the duration of wounds. ^[5]

• Cell lines

  neonatal rat cardiomyocytes

• Concentrations

  30 μM

• Incubation Time

  3 h

• Method

  Neonatal rat cardiomyocytes are pre-incubated with dexrazoxane (DEX), sobuzoxane (SOB) or merbarone (MER) for 3 h and then incubated with anthracyclines daunorubicin or doxorubicin for 3 h following a 48-h anthracycline-free period or for 48 h with hydrogen peroxide (H2O2). 

• Animal Models

  female B6D2FI

• Dosages

  62.5 mg/kg

• Administration

  i.p.