Abstract 463: Dietary Nitrite Plays a Role in Wound Healing in Diabetic Mice

Abstract

Intro: Diabetic wounds heal poorly leading to major morbidity, mortality, and financial cost. Nitric oxide (NO), produced in wounds by NO synthases (NOSs), is essential for normal wound healing and is reduced in diabetic wounds, contributing to poor healing. It is known that NO can also be regenerated from nitrite through xanthine oxidoreductase (XOR). Thus, we hypothesize that dietary nitrite may be an important source of NO in diabetic wound healing. Methods: Diabetic Db/Db mice were fed normal chow, nitrite depleted chow, or nitrite depleted chow with 1.5g/L nitrite supplemented water starting 1 week prior to wounding. Excisional wounds were created on each mouse and wound areas were measured every other day. Skin and wound samples from a separate group of Db/Db mice were obtained prior to and 5 days after wounding. Tissues were used for Western blots and XOR activity assay. Plasma was used for nitrite measurements. Results: Nitrite depletion lowered plasma nitrite by 50-60% vs mice on chow or on nitrite water. XOR was highly expressed in the skin, less so at the wound edge, and minimally in granulation tissue by Western. This was confirmed by XOR enzyme assay showing 5 fold more activity in the skin compared to the wound tissues. Wound healing was delayed in nitrite depleted mice as compared to the chow fed mice (Figure). Nitrite supplementation showed a trend in improved healing rates vs nitrite depleted mice. Conclusion: Diabetic skin and wound edge expresses XOR. Nitrite does contribute to wound healing in Db/Db mice. Dietary nitrite increased plasma nitrite levels and increased the wound healing rate. This suggests a potential therapeutic role for dietary nitrite in diabetic wound care.