+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Nitric oxide enhances experimental wound healing in diabetes



Nitric oxide enhances experimental wound healing in diabetes



British Journal of Surgery 89(12): 1594-1601



Diabetes is characterized by a nitric oxide deficiency at the wound site. This study investigated whether exogenous nitric oxide supplementation with the nitric oxide donor molsidomine (N-ethoxycarbomyl-3-morpholinyl-sidnonimine) could reverse the impaired healing in diabetes. Wound healing was studied by creating a dorsal skin incision with subcutaneous polyvinyl alcohol sponge implantation in diabetic and non-diabetic rats. Half of each group was treated with molsidomine. Collagen metabolism was assessed by wound breaking strength, hydroxyproline (OHP) content, RNA expression for collagen type I and III, and matrix metalloproteinase (MMP) 2 activity in wound sponges. Wound fluid, plasma and urinary nitric oxide metabolite levels, and the number of inflammatory cells were assessed. OHP content and wound breaking strength were significantly increased by molsidomine. MMP-2 activity in wound fluid was decreased in diabetes and upregulated by nitric oxide donors. The impaired inflammatory reaction in diabetes was unaffected by nitric oxide donor treatment and ex vivo nitric oxide synthesis was no different between wound macrophages from control and diabetic animals, suggesting that the nitric oxide deficiency in the wound is due to a smaller inflammatory reaction in diabetes. The nitric oxide donor molsidomine can at least partially reverse impaired healing associated with diabetes.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 046805395

Download citation: RISBibTeXText

PMID: 12445072

DOI: 10.1046/j.1365-2168.2002.02263.x


Related references

L-Arginine supplementation enhances diabetic wound healing: involvement of the nitric oxide synthase and arginase pathways. Metabolism: Clinical and Experimental 51(10): 1269-1273, 2002

Supplemental dietary arginine enhances wound healing in normal but not inducible nitric oxide synthase knockout mice. Surgery 128(2): 374-378, 2000

Diabetes-impaired healing and reduced wound nitric oxide synthesis: A possible pathophysiologic correlation. Surgery (St Louis) 121(5): 513-519, 1997

Simvastatin enhances VEGF production and ameliorates impaired wound healing in experimental diabetes. Pharmacological Research 57(2): 159-169, 2008

Sonic hedgehog improves delayed wound healing via enhancing cutaneous nitric oxide function in diabetes. American Journal of Physiology. Endocrinology and Metabolism 297(2): E525-E531, 2009

Low-energy extracorporeal shock wave therapy enhances skin wound healing in diabetic mice: a critical role of endothelial nitric oxide synthase. Wound Repair and Regeneration 20(6): 887-895, 2013

Substance P and nitric oxide mediate wound healing of ultraviolet photodamaged rat skin: Evidence for an effect of nitric oxide on keratinocyte proliferation. Neuroscience Letters 200(1): 17-20, 1995

Epidermal growth factor suppresses nitric oxide and hydrogen peroxide production by keratinocytes. Potential role for nitric oxide in the regulation of wound healing. Journal of Biological Chemistry 267(30): 21277-21280, 1992

Addition of nitric oxide through nitric oxide-paracetamol enhances healing rat achilles tendon. Clinical Orthopaedics and Related Research 466(7): 1618-1624, 2008

Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity. International Journal of Nanomedicine 10: 3065-3080, 2015

Nitric oxide synthase inhibitors appear to improve wound healing in endotoxemic rats: An investigator-blinded, controlled, experimental study. Current Therapeutic Research Clinical and Experimental 67(6): 378-385, 2006

Wound healing and nitric oxide production: too little or too much may impair healing and cause chronic wounds. International Journal of Lower Extremity Wounds 5(1): 6-8, 2006

Acute protein-calorie malnutrition impairs wound healing: a possible role of decreased wound nitric oxide synthesis. Journal of the American College of Surgeons 184(1): 37-43, 1997

Extremely low frequency electromagnetic fields modulate expression of inducible nitric oxide synthase, endothelial nitric oxide synthase and cyclooxygenase-2 in the human keratinocyte cell line HaCat: potential therapeutic effects in wound healing. British Journal of Dermatology 162(2): 258-266, 2010