Modulation of Experimental Doxorubicin Skin Toxicity by β-Adrenergic Compounds

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Abstract

Doxorubicin [Adriamycin (ADM)], a potent intercalating antineoplastic agent, occasionally causes severe local skin toxicity if extravasated during administration. Previous experiments using intradermal (i.d.) ADM in BALB/c mice have shown limited antidotal activity for local i.d. corticosteroids in preventing ADM-induced ulceration and no effect for a number of other compounds except β-adrenergic agonists and antagonists. Three sequences of i.d. administration of β-adrenergics were evaluated in this study: a single dose immediately after 0.05 or 0.5 mg ADM; 8 daily doses of isoproterenol (ISO) or 0.9% NaCI solution, 0.05 ml after ADM; and 5 days of pre-ADM to ostensibly “up” or “down’ -regulate β-receptor number (with propranolol and ISO, respectively). The results demonstrate consistent antidotal activity for ISO and propranolol as single antidotal injections. Terbutaline, aO2-specific agonist, was not effective as an antidote. Continuous daily ISO did not improve results, whereas continuous i.d. NaCI solution significantly increased skin lesion size and duration. ISO pretreatment significantly decreased subsequent ADM-induced ulceration, while propranolol pretreatment was not different from control. The results confirm a role for β-adrenergics in the management of experimental ADM skin ulceration and suggest that local toxicity is mediated through specific β-receptors (possibly β1) in the mouse skin.

Original languageEnglish (US)
Pages (from-to)2428-2432
Number of pages5
JournalCancer Research
Volume41
Issue number6
StatePublished - Jun 1 1981

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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