Effect of difluoromethylornithine, a chemotherapeutic agent, on wound healing

Abstract

Introduction: Difluoromethylornithine (DFMO) is a potential chemotherapeutic agent and currently in Phase II trials for colon and prostate malignancies. DFMO will potentially be used for chemotherapy in postoperative patients in low dosage. Therefore, we studied the effect of low dosage DFMO on wound healing. Methods: Two groups of twenty male Sprague Dawley rats underwent a midline dorsal incision with implantation of polyvinyl alcohol sponges into subcutaneous pockets. In Exp 1, ten rats were injected daily with DMFO (500 mg/kg IP) starting on day of wounding while controls (ten rats) received equivalent volume of normal saline. In Exp 2, DFMO and normal saline treatments were delayed until post-wounding day 3. All rats were sacrificed on day 10 post-wounding. Incisional wound breaking strength (WBS, g) and sponge hydroxyproline (OHP, g/100mg sponge) content (collagen deposition), were assessed. Efficacy of DFMO treatment was assessed by measuring wound fluid polyamines, putrescine (PUT) and spermidine (SPER)(M) Results: Treatment with DFMO starting on day 0 (Exp 1) resulted in a significant decrease in collagen deposition and wound breaking strength. Neither of the wound healing parameters was affected when treatment was begun 3 days post-wounding (Exp 2). Conclusion: Wound healing is decreased when DFMO treatment is started on the day of surgery. This suggests that DFMO treatment may play a critical role in the synthesis of collagen in early wound healing and chemotherapy with DFMO should be delayed for patients requiring surgery. TABLE—ABSTRACT P116GroupWBSOHPPUTSPEREXP 1Control409 ± 821435 ± 10211.6 ± 3.4NDDFMO340 ± 41∗1014 ± 67∗∗2.2 ± 0.4∗∗NDEXP 2Control376 ± 941568 ± 9015.3 ± 5.295.4 ± 18.6DFMO354 ± 411624 ± 1505.7 ± 5.4∗∗63.1 ± 12.8∗∗Mean ± standard deviation.∗P < 0.05 and∗∗P < 0.005 by t-test; Student’s t-test; ND—not determined.