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.


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.


CONCLUSIONS
We have shown that pravastatin, in an experimental model of diabetes may through up-regulation of eNOS and NO expression improve wound healing.
Laing
Tereze
T
Department of Surgery, RCSI Biomedical Research Institute, Beaumont, Dublin, Ireland. terezelaing@yahoo.com
Hanson
Richard
R
Chan
Fuan
F
Bouchier-Hayes
David
D
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D017035:Pravastatin / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects / Q000503:physiopathology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*; D014947:Wounds and Injuries / Q000378:metabolism / Q000503:physiopathology*
D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D017035:Pravastatin; D006909:Hydroxyproline