Abstract 265: Oral Nitrite Supplementation Improves Rates of Wound Healing in Diabetic Mice

Abstract

Introduction: Nitric oxide (NO) is required for cutaneous wound healing. Impaired diabetic wound healing has been linked to a deficiency in local NO production and can be enhanced with NO delivery. NO is a short-lived, highly reactive molecule and local delivery is complicated by these properties. An alternate source of NO can be achieved through the ability of nitrite reductases to convert the stable NO end-product, nitrite, back to NO. We have previously demonstrated that skin and wound edge express high levels of xanthine oxidoreductase (XOR). XOR is a strong nitrite reductase. We hypothesize that dietary nitrite supplementation will improve wound healing in diabetic mice. Methods: Db/db mice (N>8/group) were pretreated for 1 week with sodium nitrite supplemented drinking water (50 mg/L), nitrite-free chow, or standard chow. Additionally, nitrite supplemented mice were gavaged with nitrite supplemented water (0.2 ml) every other day for the duration of the experiment. A 1 cm 2 excisional wound was created on the back of each mouse. Wounds were photographed every other day until closure and wound areas calculated with ImageJ and compared with ANOVA and Kaplan Meier. Results: Time to complete healing was significantly different between nitrite supplemented (NS), nitrite depleted (ND), and control mice (18.9±0.7, 21.6±3.3, and 23±3.5 days, respectively, P = 0.035). NS mice reached 75% and 100% healed faster than ND or control mice (P = .009 and P = .042, respectively) [Figure]. Initial wound expansion on day 2 was decreased in NS mice compared to ND mice. XOR activity was increased in wounds compared to skin but similar between all treatment groups. Conclusion: Nitric oxide is a critical component of wound healing. Oral systemic nitrite supplementation improves diabetic wound healing in mice. Dietary nitrite may be an inexpensive and safe method of augmenting NO production through wound XOR expression to improve wound repair.