Dexrazoxane's protection of jejunal crypt cells in the jejunum of C3Hf/Kam mice from doxorubicin-induced toxicity

Dexrazoxane (DEX) is used clinically to reduce doxorubicin-induced cardiotoxicity. Because DEX inhibits anthracycline-induced toxicity, we set out to investigate DEX's ability to reduce the incidence and severity of gastrointestinal toxicity associated with anthracycline administration in C3Hf/Kam mice. Doxorubicin and idarubicin, two commonly used anthracyclines, were each examined in combination with DEX. A jejunal crypt survival assay demonstrated that DEX increased crypt survival from 40% (doxorubicin 22.5 mg/kg) to 63% at a DEX/doxorubucin dose ratio of 10:1 (P<0.05). When doxorubicin was increased to a dose of 27.5 mg/kg, crypt survival increased from 18% to 40% at a DEX:Dox ratio of 5:1 (P<0.05). At ratios of 10:1 and 20:1, DEX had no protective effect on idarubicin-induced crypt cell toxicity. Our findings support the use of DEX to prevent or ameliorate mucositis in patients receiving anthracycline-based therapy and the use of DEX with high-dose doxorubicin to treat refractory disease.