Nitric Oxide Donor (deta Nonoate) Enhance Experimental Wound Healing in Streptozotocin-induced Diabetic Rats

Background: Diabetes is characterized by a nitric oxide deficiency at the wound site. Diabetes is a factor that influences all stages of wound healing. In animals with acute experimental diabetes induced by streptozotocin (STZ), the early inflammatory responses after wounding is impaired, fibroblast and endothelial cell proliferation is reduced as well as accumulation of reparative collagen and gain in wound breaking strength. In this study we investigated whether exogenous nitric oxide supplimentation with nitric oxide donor DETA NONOate could reverse impaired healing in diabetes. Method: In this study male Sprague Dawley Rats were rendered diabetic by intraperitoneal streptozotocin administration. Nine days after induction of diabetes (blood glucose greater than 250 mg/dl), were given full thickness dermal wounds (1×1cm). The test group (n=6) was treated with 100μ mole DETA NONOate in phosphate buffer while control wounds in the control subjects (n=6) received sterile phosphate buffer on the same day and subsequently every three days. Urinary nitrate output was quantitated daily prior to wounding, during wound healing (21 days) and following external wound closure. The rate of wound healing was determined by video image analysis on the day of wounding and every 3 days during wound healing (21days). Result: The results suggest nitric oxide donor DETA NONOate can reverse impaired healing associated with diabetes (P<0.001) and urinary nitrate (NO3) output may reflect the extent of repair in this wound model (P<0.001). Conclusion: Site specific delivery of nitric oxide via NO-donor DETA NONOate could be an effective therepeutic strategy to impaired diabetic wound healing.