Effect of allopurinol on adriamycin-induced impairment of wound healing.
Use of antineoplastic drugs perioperatively requires an understanding of their potential effects on healing wounds. Adriamycin is an antineoplastic drug with a wide range of antitumor activity. Prior studies have demonstrated that adriamycin impairs skin wound healing but these studies have offered limited explanations for the mechanism of action of the drug vis á vis impairment of healing wounds. In this study we investigated the effect of a xanthine oxidase inhibitor, allopurinol, on adriamycin-induced tissue injury to determine the role oxyradicals might play in reducing wound-breaking strength. Sixty-four Buffalo rats were studied. Eight animals were used to establish drug tolerances. Fifty-six animals were divided into four experimental groups; saline control (2 mL IP), allopurinol control (4.3 mg/kg po), allopurinol-adriamycin (4.3 mg/kg po + 6 mg/kg IV, respectively), and adriamycin (6 mg/kg IV). Animals treated with adriamycin alone had significantly reduced weight at postoperative day (POD) 7 compared to control groups (p less than .025). Bowel-bursting strength (BBS) of the animals treated with adriamycin alone was also significantly decreased at POD 7, compared to controls (p less than .025), and by POD 14 the animals treated with adriamycin alone had a significantly decreased fascial tensile strength, compared to the saline control (p less than .05). At no point did the animals treated with both allopurinol and adriamycin show a significantly decreased weight, BBS, or fascial tensile strength compared to control animals. Allopurinol appeared to protect against adriamycin toxicity on healing wounds. These results suggest that xanthine oxidase and possibly superoxide radicals play an important role in mediating adriamycin toxicity on healing wounds.
Johnson
H
H
Department of Surgery, Long Island Jewish Medical Center, New Hyde Park, NY 11042.
Zelnick
R
R
Davis
E
E
Wise
L
L
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D002432:Cecum / Q000502:physiology; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D006909:Hydroxyproline / Q000032:analysis; D011506:Proteins / Q000032:analysis; D051381:Rats; D011915:Rats, Inbred BUF; D014945:Wound Healing / Q000187:drug effects*
D011506:Proteins; D000493:Allopurinol; D004317:Doxorubicin; D006909:Hydroxyproline