CYTOPROTECTIVE EFFECTS OF EPIDERMAL GROWTH-FACTOR (EGF) OINTMENT CONTAINING NAFAMOSTAT, A PROTEASE INHIBITOR, ON TISSUE-DAMAGE AT BURN SITES IN RATS

When epidermal growth factor (EGF) ointment containing a protease inhi bitor, nafamostat (NM), was applied to burn sites in rats, the superox ide dismutase (SOD) enzyme activity and protein content increased 45% and 60%, respectively, at these sites 1 d after the bums compared with the control ointment. Following treatment with EGF plus NM (EGF + NM) ointment, messenger RNA for SOD also increased, to about 1.6 times th at of the control at 1 d after the burn, indicating that this ointment stimulates SOD synthesis at burn sites in vivo. In contrast, followin g treatment with EGF + NM ointment, the content of heat shock protein (HSP 70) in the burned tissue decreased to about 70% of the control va lue 1 d after the burn. These findings suggest that EGF + NM ointment alleviated tissue damage at burn sites at an early stage, and that thi s was related to the stimulation of SOD synthesis and reduced HSP 70 l evels. We also examined the effects of SOD ointment on wound healing a t burn sites. A dose-dependent increase in the dry weight of granulati on tissue at wound sites 3d after the burn was observed following the application of this ointment. These results suggest that SOD may play an important role in wound healing after burns.