Topical diphenylhydantoin sodium can improve healing in a diabetic incisional animal wound model.
OBJECTIVE
Anecdotally, topical application of diphenylhydantoin sodium (DpH) (phenytoin) has been shown to aid wound healing. We previously reported improved healing following topical infiltration of DpH in a healthy animal wound model. This study evaluates its effect on an incisional wound model in diabetic animals.


METHODS
Twenty-five male Sprague-Dawley rats were rendered diabetic by a single intraperitoneal injection of streptozotocin. Two caudal and two cephalad wounds were made on the dorsal surface. A polyvinyl alcohol sponge was placed in a subcutaneous pocket created proximal to both cephalad wounds. Each wound was either treated topically with 10mg DpH in a 200microl carrier or an equal volume of the saline vehicle (control) on the day of wounding and days 3 and 6 post-incision. The animals were sacrificed on day 10. The breaking strength of fresh and fixed wounds was determined by tensiometry, and the hydroxyproline content was determined spectrophotometrically.


RESULTS
There was a significant overall increase in both fresh (24%) and fixed (18%) wound-breaking strength of the DpH-treated wounds when compared with the controls (p<0.05). This was associated with an increase in collagen synthesis as indicated by the increased hydroxyproline content in the DpH-infiltrated sponges when compared with the controls.


CONCLUSIONS
Our data suggest that topical DpH improves healing in a diabetic wound model. Topical administration of DpH has the potential to accelerate diabetic wound healing and should be evaluated in human diabetic wounds.
Chan
F C
FC
Department of Surgical Research, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland. fchan@rcsi.ie
Kennedy
C
C
Hanson
R P
RP
O'Sullivan
B
B
Kelly
J
J
Bouchier-Hayes
D
D
D000818:Animals; D003094:Collagen / Q000032:analysis / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006909:Hydroxyproline / Q000032:analysis / Q000187:drug effects; D007150:Immunohistochemistry; D007271:Injections, Intradermal; D008297:Male; D010672:Phenytoin / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000627:therapeutic use; D013053:Spectrophotometry; D013311:Streptozocin; D013718:Tensile Strength; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*; D014950:Wounds, Penetrating / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
D012965:Sodium Chloride; D013311:Streptozocin; D010672:Phenytoin; D003094:Collagen; D006909:Hydroxyproline