A comparative study to evaluate the effect of limited access dressing on diabetic ulcers

Abstract

Aim: Emerging evidence favors the important role of antioxidants, matrix metalloproteinases (MMPs) and nitric oxide (NO) in the healing of diabetic wounds. There is a lack of substantial evidence regarding the effects of negative pressure on antioxidants, MMPs and NO in chronic wounds associated with diabetes.

Methods: A total of 55 type 2 diabetic patients with leg ulcers were divided into 2 groups: a limited access dressing (LAD) group (n = 27) and a conventional dressing group (n = 28). Levels of hydroxyproline, total protein, MMP-2 and MMP-9, NO and antioxidants including reduced glutathione (GSH), and the oxidative biomarker malondialdhyde (MDA) were measured in the granulation tissue at days 0 and 10. Changes in levels between the LAD and conventional groups were determined by the student's t-test.

Results: After 10 days of treatment, the LAD vs. conventional dressing group showed increases in the levels of hydroxyproline (mean ± SD = 55.2 ± 25.1 vs. 29.2 ± 1; P < 0.05), total protein (12.8 ± 6.5 vs. 8.34 ± 3.2; P < 0.05), NO (1.13 ± 0.52 vs. 0.66 ± 0.43; P < 0.05), GSH (7.0 ± 2.4 vs. 6.6 ± 2.2; P < 0.05) and decreases in MMP-2 (0.47 ± 0.33 vs. 0.62 ± 0.30; P < 0.05), MMP-9 (0.32 ± 0.20 vs.0.53 ± 0.39; P < 0.05) and MDA (6.8 ± 2.3 vs. 10.4 ± 3.4; P < 0.05).

Conclusion: When compared to conventional dressings, LAD induces biochemical changes by significantly increasing the levels of hydroxyproline, total protein, NO and antioxidants levels, and significantly reducing MMPs (MMP-2 and MMP-9) and an oxidative biomarker in diabetic wounds. These biochemical changes are thought to favor diabetic wound healing.

Keywords

Antioxidants / diabetic wounds / hydroxyproline / limited access dressing / matrix metalloproteinases / nitric oxide / reactive oxygen species and oxidative stress biomarker / total protein

References

[1] Singer AJ.Cutaneous wound healing..N Engl J Med1999;341:738-46

[2] Eming SA,Davidson JM.Inflammation in wound repair: molecular and cellular mechanisms..J Invest Dermatol2007;127:514-25

[3] Khodr B.Modulation of inflammation by reactive oxygen species: implications for aging and tissue repair..Free Radic Biol Med2001;30:1-8

[4] Hallberg CK,Ansari NH.Acceleration of corneal wound healing in diabetic rats by the antioxidant Trolox..Res Comm Mol Pathol Pharmacol1996;93:3-12

[5] McDaniel DH,Lord J,Zukowski M.Accelerated laser resurfacing wound healing using a triad of topical antioxidants..Dermatol Surg1998;24:661-4

[6] Madlener M,Werner S.Matrix metalloproteinases and their physiological inhibitors (TIMPs) are differentially expressed during excisional skin wound repair..Exp Cell Res1998;242:201-10

[7] Kakkar R,Mantha SV.Lipid peroxidation and activity of antioxidant enzymes in diabetic rats..Mol Cell Biochem1995;151:113-9

[8] Wiseman H.Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer..Biochem J1996;313:17-29 PMCID:PMC1216878

[9] Sivitz WI.Mitochondrial dysfunction in Diabetes: from molecular mechanisms to functional significance and therapeutic opportunities..Antioxid Redox Signal2010;12:537-77 PMCID:PMC2824521

[10] Rolo AP.Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress..Toxicol Appl Pharmacol2006;212:167-78

[11] Guo S.Factors affecting wound healing..J Dent Res2010;89:219-29 PMCID:PMC2903966

[12] Hsu WT,Lin SK,Chen BH.Effects of diabetes duration and glycemic control on free radicals in children with type1 diabetes mellitus..Ann Clin Lab Sci2006;36:174-8

[13] Flora SJ.Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure..Oxid Med Cell Longev2009;2:191-206 PMCID:PMC2763257

[14] Valko M,Moncol J,Mazur M.Free radicals and antioxidants in normal physiological functions and human disease..Int J Biochem Cell Biol2007;39:44-84

[15] Honnegowda TM,Udupa P,Bhandary S,Sharan A.Effect of limited access dressing on hydroxyproline and enzymatic antioxidant status in nonhealing chronic ulcers..Indian J Plast Surg2014;47:216-20 PMCID:PMC4147456

[16] Polack G,Tyner T,Vu K,Merriman J,Hasson A,Yamaguchi KT.Accelerated wound closure in a diabetic mouse model after exposure to phenanthrenequinone..Ann Plast Surg2013;70:720-5

[17] Blume PA,Payne W,Lantis J.Comparison of negative pressure wound therapy using vacuum-assisted closure with advanced moist wound therapy in the treatment of diabetic foot ulcers: a multicenter randomized controlled trial..Diabetes Care2008;31:631-66

[18] Neuman RE.The determination of collagen and elastin in tissues..J Biol Chem1950;86:549-56

[19] Lowry OH,Farr L.Protein measurement with the Folin phenol reagent..J Biol Chem1951;193:265-75

[20] Young PK.Metalloproteinase activation cascade after burn injury: a longitudinal analysis of the human wound environment..J Invest Dermatol1994;103:660-4

[21] Green LC,Glogowski J,Wishnok JS.Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids..Anal Biochem1982;126:131-8

[22] Beutler E,Kefly BM.Improved method for the determination of blood glutathione..J Lab Clin Med1963;61:882-8

[23] Ohkawa H,Yagi K.Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction..Anal Biochem1979;95:351-8

[24] Abd-El-Aleem SA,Appleton I,Jude EB,Mc Collum CN.Expression of nitric oxide synthase isoforms and arginase in normal human skin and chronic venous leg ulcers..J Pathol2000;191:434-42

[25] Rojkind M,Nieto N.Role of hydrogen peroxide and oxidative stress in healing responses..Cell Mol Life Sci2002;59:1872-91

[26] Moseley R,Waddington RJ,Stephens P.Comparison of oxidative stress biomarker profiles between acute and chronic wound environments..Wound Repair Regen2004;12:419-29

[27] Joseph E,Bergman S,Swann NF.A prospective randomized trial of vacuum-assisted closure versus standard therapy of chronic nonhealing wounds..Wounds2000;12:60-7

[28] Kumar P.Exploiting potency of negative pressure in wound dressing using limited access dressing and suction-assisted dressing..Indian J Plast Surg2012;45:302-15 PMCID:PMC3495381

[29] Kumar P.The limited access dressing for damage control in trauma patients..Wounds2010;22:188-92

[30] Rasik AM.Antioxidant status in delayed healing type of wounds..Int J Exp Pathol2000;81:257-63 PMCID:PMC2517731

[31] Tengrup I,Agren MS.Granulation tissue formation and metabolism of zinc and copper in alloxan-diabetic rats..Scand J Plast Reconstr Surg Hand Surg1988;22:41-5

[32] Spanheimer RG,Stumpf V.Decreased collagen production in diabetic rats..Diabetes1988;37:371-6

[33] Honnegowda TM,Padmanabha Udupa EG,Singh R,Rao P.Effects of limited access dressing in chronic wounds: A biochemical and histological study..Indian J Plast Surg2015;48:22-8 PMCID:PMC4413484

[34] Lobmann R,Schultz G,Schiweck S.Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients..Diabetologia2002;45:1011-6

[35] Liu Y,Bolton T,Twigg SM,McLennan SV.Increased matrix metalloproteinase-9 predicts poor wound healing in diabetic foot ulcers..Diabetes Care2009;32:117-9 PMCID:PMC2606842

[36] Boykin JV, Jr..Wound nitric oxide bioactivity: a promising diagnostic indicator for diabetic foot ulcer management..J Wound Ostomy Continence Nurs2010;37:25-32

[37] Johansen JS,Rychly DJ.Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice..Cardiovasc Diabetol2005;4:5 PMCID:PMC1131912

[38] Honório-França AC,Boldrini F.Evaluation of hypoglycemic activity and healing of extract from amongst bark of "Quina do Cerrado" (Strychnos pseudoquina ST. HILL)..Acta Cir Bras2008;23:504-10

[39] Ceriello A,Caretta F,Giugliano D.Evidence for a possible role of oxygen free radicals in the abnormal functional arterial vasomotion in insulin dependent diabetes..Diabete Metab1990;16:318-22

[40] Fouad Al-Bayaty.A Comparison of Wound Healing Rate Following Treatment with Aftamed and Chlorine Dioxide Gels in Streptozotocin-Induced Diabetic Rats..Evid Based Complement Alternat Med2012;2012:468764 PMCID:PMC3362038