Glucocorticoid-dependent impairment of wound healing in experimental diabetes: Amelioration by adrenalectomy and RU 486

Background. Failure of wounds to heal represents one of the major diabetic complications. Emerging evidence favors the involvement of glucocorticoids (GCs) in the pathogenesis of impaired wound healing in diabetes mellitus. Objective. The purpose of this study was to examine wound healing potential in diabetics under conditions in which the hypercortisolemic state is norm alized. Design and intervention, Linear skin incision and polyvinyl alcohol (PVA) s ponge were used as wound healing models. Six groups of rats matched with re spect to age, sex, and strain were included in this study. Animals in group s 1 and 6 were injected with citrate buffer, whereas rats in groups 2,3,4, and 5 received streptozotocin (STZ, 55 mg/kg iv in citrate buffer). Five da ys later animals in groups 4,5, and 6 received insulin (group 4) and subcut aneous implantation of slow-releasing pellets containing either the GC rece ptor blocker RU 486 (group 5) or a high dose of GC (group 6). Main outcome measurements. Skin wound tensile strength and PVA sponge colla gen metabolism were determined using tensiometric, spectrosphotometric, and polymerase chain reaction-based assays. In addition, cell infiltration and granulation tissue growth were assessed using a well-established histochem ical technique. Results. Wound-related parameters including fibroplasia, neovascularization , and inflammatory cell numbers were reduced as a function of diabetes. Sim ilarly, skin mound tensile strength, PVA sponge hydroxyproline content, and the levels of mRNA transcripts for type I and LII collagen were also decre ased in this disease state. This diabetes-related deficit in wound healing potential was ameliorated by subjecting diabetic animals to insulin treatme nt or by counteracting the excessive actions of GCs using both pharmacologi cal (RU 486) and endocrinological (ADX) paradigms. Conclusion. The current study supports the notion that GCs are implicated i n the wound healing deficit of diabetics. Moreover, it illuminates the ther apeutic potential of the GC receptor blocker (e.g., RU 486) in promoting mo und repair wider hypercortisolemic conditions including diabetes and Gushin g's syndrome. (C) 199 Academic Press.