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.
Pearlman
Michael
M
Departments of Leukemia and Special Medical Educations Program-Unit 55, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
Jendiroba
David
D
Pagliaro
Lance
L
Keyhani
Afsaneh
A
Liu
Baoshun
B
Freireich
Emil J
EJ
Travis
Elizabeth
E
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity*; D015255:Idarubicin / Q000633:toxicity; D007274:Injections, Intraperitoneal; D007579:Jejunal Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007583:Jejunum / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D020011:Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011929:Razoxane / Q000008:administration & dosage / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D020011:Protective Agents; D011929:Razoxane; D004317:Doxorubicin; D015255:Idarubicin