OBJECTIVE: This study compared the potencies of the antifibrotic agents mitomycin C (MMC) and halofuginone (HFN) and investigated whether coadministration of these agents produces synergic effects in an animal skin wound model. SUBJECTS AND METHODS: Twenty male Sprague-Dawley rats were used for this study. After a full-thickness excisional wound was made on the dorsum of each rat, each rat was treated with topical mitomycin, intraperitoneal HFN, or both. Wound surface areas were measured over time, and histologic analysis was performed after wounds healed completely. RESULTS: The groups treated with MMC alone, HFN alone, and a combination of the two all exhibited delayed wound healing compared with the untreated group. Histologically, fibrosis and matrix metalloproteinase-2 expression were significantly inhibited in the treated groups. However, there were no gross or histologic differences between the MMC-treated group, the HFN-treated group, and the combination-treatment group. CONCLUSIONS: Both MMC and HFN inhibited excessive fibrosis. However, there was no significant difference in the antifibrotic effects of MMC and HFN on surgically induced skin wounds. Moreover, combination treatment with both MMC and HFN failed to confer an additional antifibrotic effect on skin wounds when compared with treatment with MMC or HFN alone. Crown
OBJECTIVE: This study compared the potencies of the antifibrotic agents mitomycin C (MMC) and halofuginone (HFN) and investigated whether coadministration of these agents produces synergic effects in an animal skin wound model. SUBJECTS AND METHODS: Twenty male Sprague-Dawley rats were used for this study. After a full-thickness excisional wound was made on the dorsum of each rat, each rat was treated with topical mitomycin, intraperitoneal HFN, or both. Wound surface areas were measured over time, and histologic analysis was performed after wounds healed completely. RESULTS: The groups treated with MMC alone, HFN alone, and a combination of the two all exhibited delayed wound healing compared with the untreated group. Histologically, fibrosis and matrix metalloproteinase-2 expression were significantly inhibited in the treated groups. However, there were no gross or histologic differences between the MMC-treated group, the HFN-treated group, and the combination-treatment group. CONCLUSIONS: Both MMC and HFN inhibited excessive fibrosis. However, there was no significant difference in the antifibrotic effects of MMC and HFN on surgically induced skin wounds. Moreover, combination treatment with both MMC and HFN failed to confer an additional antifibrotic effect on skin wounds when compared with treatment with MMC or HFN alone. Crown