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Effect of allopurinol on adriamycin-induced impairment of wound healing
Abstract:
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.
Insights
Allopurinol protects against Adriamycin-induced wound healing impairment by inhibiting xanthine oxidase and superoxide radicals. This study suggests a key role for oxyradicals in Adriamycin
Area of Science:
- Wound healing research
- Pharmacology
- Biochemistry
Background:
- Antineoplastic drugs like Adriamycin can impede wound healing.
- The precise mechanism by which Adriamycin affects wound healing remains unclear.
- Oxyradicals are implicated in various tissue injuries.
Purpose of the Study:
- To investigate the role of oxyradicals in Adriamycin-induced impairment of wound healing.
- To determine if allopurinol, a xanthine oxidase inhibitor, can mitigate Adriamycin's negative effects on wound strength.
Main Methods:
- Sixty-four Buffalo rats were used in four experimental groups: saline control, allopurinol control, allopurinol-Adriamycin, and Adriamycin alone.
- Drug tolerances were established in eight animals.
- Wound healing was assessed by monitoring animal weight, bowel-bursting strength (BBS), and fascial tensile strength at specific postoperative days.
Main Results:
- Adriamycin alone significantly reduced animal weight and BBS by postoperative day 7, and fascial tensile strength by day 14.
- Animals treated with both allopurinol and Adriamycin did not exhibit significant reductions in weight, BBS, or fascial tensile strength compared to controls.
- Allopurinol demonstrated a protective effect against Adriamycin-induced toxicity on healing wounds.
Conclusions:
- Xanthine oxidase and superoxide radicals likely play a significant role in Adriamycin's toxicity to healing wounds.
- Allopurinol may serve as a protective agent against Adriamycin's detrimental effects on wound healing.
- Targeting oxyradical pathways could be a therapeutic strategy to improve wound healing in patients receiving Adriamycin.