Improvement in wound healing by epidermal growth factor (EGF) ointment. II. Effect of protease inhibitor, nafamostat, on stabilization and efficacy of EGF in burn.

The healing effect of human epidermal growth factor (hEGF) on second degree burn was studied in rats. No improvement in wound healing was found on topical application of EGF alone to burn sites, but an ointment containing EGF and nafamostat mesilate (NM), a protease inhibitor, accelerated the healing rate of burns. The dry weight of the granulation tissue on the wound site in the group treated with EGF plus NM ointment did not change, although that in other groups decreased. After treatment with EGF ointment containing NM, the content of uronic acid, as an index of acid mucopolysaccharide, at 3 d after burn rapidly increased and had recovered to nearly normal levels at 7 d after burn. However, the uronic acid content in the other groups (control, EGF alone, and NM alone) showed a higher value at 7 d than at 3 d. When compared with the control values significant increases in hydroxyproline, as an index of collagen, in the wound site were observed at 7 d after treatment with EGF ointment containing NM. The degradation of [125I]EGF in burned tissue homogenate decreased significantly in a concentration-dependent manner in the presence of NM. Body weights did not change after treatment with EGF plus NM ointment, although the body weights of other treatment groups decreased after burn, suggesting that EGF ointment containing the protease inhibitor, NM, alleviated the effects of burn shock. These findings indicate that the stabilization of EGF at the wound site is an important factor for the expression of its healing effects.