Pharmacologic antidotes to experimental doxorubicin skin toxicity: a suggested role for beta-adrenergic compounds.
Doxorubicin (ADM) skin toxicity is a serious complication of inadvertent perivenous drug infiltrations. In an attempt to attempt to identify possible antidotes, nine diverse pharmacologic agents were injected intradermally into the hair-free dorsum of BALB/c mice following an intradermal ADM dose of either 0.05 or 0.5 mg. Seven of the compounds were ineffective in reducing ADM-induced ulceration; the compounds included lidocaine, cimetidine, diphenhydramine, sodium heparin, hyaluronidase, N-acetylcysteine, and alpha-diphenhydramine, sodium heparin, hyaluronidase, N-acetylcysteine, and alpha-tocopherol. The latter five compounds actually increased ulceration induced by ADM (0.5 mg), especially N-acetylcysteine, which tripled the total toxic effect. Two opposing beta-adrenergic compounds, the antagonist propranolol and the agonist isoproterenol, reduced skin ulceration resulting from experimental treatment with intradermal ADM. A role for the beta-adrenergic receptor in mediating ADM-induced skin ulceration is suggested.
D000818:Animals; D004317:Doxorubicin / Q000009:adverse effects*; D005260:Female; D007545:Isoproterenol / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D011433:Propranolol / Q000627:therapeutic use*; D012883:Skin Ulcer / Q000139:chemically induced* / Q000188:drug therapy
D004317:Doxorubicin; D011433:Propranolol; D007545:Isoproterenol