Differential effects of 21-aminosteroids on wound healing.
OBJECTIVE
The aim of this study was to examine the effects of the 21-aminosteroid U74389F on wound healing, compared with corticosteroids using a murine incisional wound model.


BACKGROUND
The 21-aminosteroids are extremely potent inhibitors of iron-dependent lipid peroxidation and peroxyl radical formation, and have proven significantly beneficial in reducing neurologic sequelae following head and spinal cord trauma in experimental models. The detrimental effects of currently administered corticosteroids on wound healing are well-documented; however, the effects of the 21-aminosteroids on wound healing are poorly defined to date.


METHODS
Male BDF1 mice (n = 28/group) given a left paraspinous wound received daily intraperitoneal injection of vehicle or U74389F (1 to 100 mg/kg/day) for 10 days. Wound disruption strengths (WDSs) in grams were determined on freshly harvested (F) and 36-hour formalin-fixed (FF) wounds. In addition, U74389F (3 mg/kg/day) was compared with equipotent doses of methylprednisolone, dexamethasone, and hydrocortisone (n = 12/group) for alterations in wound healing.


RESULTS
The WDSs of the U74389F animals F or following FF were not significantly different from controls. In the comparison study, no significant difference in F or FF WDS was found for U74389F (3 mg/kg/day) or methylprednisolone animals when compared with controls. Dexamethasone-treated and hydrocortisone-treated animals had F and FF WDSs that were 50% of control and U74389F values (p < 0.001; ANOVA). Wounds harvested from both the control and U74389F-treated animals demonstrated the greatest extent of wound cleft contraction, collagen deposition, and neovascularity, with no obvious internal differences detectable under light microscopy.


CONCLUSIONS
These results show that the 21-aminosteroid U74389F did not impair wound healing, as determined by WDS and light microscopy. Furthermore, given their greater efficacy in cell membrane stabilization and potent ability to scavenge peroxyl radicals, the 21-aminosteroids may prove beneficial in treating a variety of clinical conditions, wherein ischemia-reperfusion injury plays a major component.
Paxton
T P
TP
Loyola University Shock Trauma Institute, Loyola University Medical Center, Maywood, IL 60153, USA.
Miles
R H
RH
Gamelli
R L
RL
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D011281:Pregnatrienes / Q000494:pharmacology* / Q000627:therapeutic use; D014945:Wound Healing / Q000187:drug effects*
D000975:Antioxidants; D011281:Pregnatrienes; C074965:U 74389F; D008775:Methylprednisolone