Effect of Pravastatin on Experimental Diabetic Wound Healing

Background. Impaired wound healing in diabetes has been associated with abnormalities in wound nitric oxide (NO) and nitric oxide synthase (NOS) availability. Efforts to alter the profile of NO expression in the wound microenvironment have proven to be successful in partially restoring wound healing deficits. We investigated the effects of pravastatin, a HMG Co A reductase inhibitor on endothelial nitric oxide synthase (eNOS) expression, NO production, and wound healing in a diabetic acute wound healing model. Materials and Methods. Of 70 male Sprague Dawley rats injected with streptozocin, 62 were confirmed diabetic after 1 wk. Animals were randomized into two groups: (1) diabetic control and (2) diabetic treated with pravastatin. Pravastatin sodium was gavaged at 0.4 mg/kg/d for 5 d, after which all animals underwent dorsal incision with insertion of subcutaneous sponges. Breaking strengths and hydroxyproline were measured on days 1, 3, and 10 post-wounding. Wound fluid was analyzed for nitrate/nitrite production. Tissue samples were analyzed for eNOS expression. Results. We demonstrated enhanced wound breaking strengths, hydroxyproline accumulation, an up-regulation in eNOS expression, and elevated NO levels in the pravastatin treated group. Conclusion. We have shown that pravastatin, in an experimental model of diabetes may through up-regulation of eNOS and NO expression improve wound healing. (C) 2010 Published by Elsevier Inc.