Acta Vet. Brno 2018, 87: 309-320

Effect of n-3 long-chain polyunsaturated fatty acids on wound healing using animal models – a review

Tomáš Komprda

Mendel University in Brno, Department of Food Technology, Brno, Czech Republic

Received April 11, 2018
Accepted December 7, 2018


1. Amadeu T, Braune A, Mandarim-de-Lacerda C, Porto LC, Desmoulière A, Costa A 2003: Vascularization pattern in hyperthrophic scars and keloids: A stereological analysis. Pathol Res Pract 199: 469-473 <>
2. Amadeu TP, Seabra AB, de Oliveira MG, Costa AM 2007: S-nitrosoglutathione-containing Hydrogel accelerates rat cutaneous wound repair. J Eur Acad Dermatol Venereol 21: 629-637
3. Arai T, Kim HJ, Chiba H, Matsumoto A 2009: Anti-obesity effect of fish oil and fish oil-fenofibrate combination in female KK mice. J Atheroscler Thromb 16: 674-683 <>
4. Arantes EL, Dragano N, Ramalho A, Vitorino D, de Souza GF, Lima MH, Velloso LA, Araújo EP 2016: Topical docosahexaenoic acid (DHA) accelerates skin wound healing in rats and activates GPR120. Biol Res Nutr 18: 411-419
5. Arita M, Yoshida M, Hong S, Tjonahen E, Glickman JN, Petasis NA, Blumberg RS, Serhan CN 2005: Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protect against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc Nat Acad Sci 102: 7671-7676 <>
6. Baddeley AJ, Gundersen HJG, Crus-Orive LM 1986: Estimation of surface area from vertical sections. J Microsc 142: 259-276 <>
7. Barberger-Gateau P, Letenneur L, Deschamps V, Peres K, Dartigues JF, Renaud S 2002: Fish, meat and risk of dementia: cohort study. Brit Med J 325: 932-933 <>
8. Caetano GF, Fronza M, Leite MN, Gomes A, Cipriani Frade MA 2016: Comparison of collagen content in skin wounds evaluated by biochemical assay and by computer-aided histomorphometric analysis. Pharm Biol 54: 2555-2559 <>
9. Campos AC, Groth AK, Branco AB 2008: Assessment and nutritional aspects of wound healing. Curr Opin Clin Nutr Metab Care 11: 281-288 <>
10. Chao CY, Lii CK, Ye SY, Li CC, Lu CY, Lin AH, Liu KL, Chen HW 2014: Docosahexaenoic acid inhibits vascular endothelial growth factor (VEGF)-induced cell migration via the GPR120/PP2A/ERK1/2/eNOS signaling pathway in human umbilical vein endothelial cells. J Agric Food Chem 62: 4152-4158 <>
11. Chen WY, Lin SY, Pan HC, Liao SL, Chuang YH, Yen YJ, Lin SY, Chen CJ 2012: Beneficial effect of docosahexaenoic acid on cholestatic liver injury in rats. J Nutr Biochem 23: 252-264 <>
12. Coelho de Castilho TJ, Campos ACL, de Souza Leite Mello EV 2015: Effect of omega-3 fatty acid in the healing process of colonic anastomosis in rats. ABCD Arq Bras Cir Dig 28: 258-261 <>
13. Colgrave ML, Allingham PG, Jones A 2008: Hydroxyproline quantification for the estimation of collagen in tissue using multiple reaction monitoring mass spectrometry. J Chromatogr A 1212: 150-153 <>
14. Cranmer-Byng MM, Liddle DM, De Boer AA, Monk JM, Robinson LE 2015: Pro-inflammatory effects of arachidonic acid in a lipopolysaccharide-induced inflammatory microenvironment in 3T3-L1 adipocytes in vitro. Appl Physiol Nutr Metab 40: 142-154 <>
15. Das U 2006: Essential fatty acids – A review. Curr Pharm Biotech 7: 467-48 <>
16. De Boer AA, Monk JM Robinson LE 2014: Docosahexaenoic acid decreases pro-inflammatory mediators in an in vitro murine adipocyte macrophage co-culture model. PLoS One 9: e85037 <>
17. Dinarello CA 2010: Anti-inflammatory agents: present and future. Cell 140: 935-950 <>
18. dos Santos Rosa A, Bandeira LG, Monte-Alto-Costa A, Romana-Souza B 2014: Supplementation with olive oil, but not fish oil, improves cutaneous wound healing in stressed mice. Wound Rep Reg 22: 537-547 <>
19. Drzymała-Czyż, Banasiewicz T, Tubacka M, Trasiuk-Rusek A, Majewski P, Drews M, Walkowiak J 2012: Discrepancy between clinical and histological effects of DHA supplementation in a rat model of pouchitis. Folia Histochem Cytobiol 50: 125-129 <>
20. Ekçi B, Karabicak I, Atukeren P, Altinlio E, Tomaoglu K, Tasci I 2011: The effect of omega-3 fatty acid and ascorbic acid on healing of ischemic colon anastomoses. Ann Ital Chir 82: 475-479
21. Figueroa JD, Cordero K, Baldeosingh K, Torrado AI, Walker RL, Miranda JD, De Leon M 2012: Docosahexaenoic acid pretreatment confers protection and functional improvements after acute spinal cord injury in adult rats. J Neurotrauma 29: 551-566 <>
22. Flock MR, Rogers CJ, Sandeep Prabhu K Kris-Etherton PM 2013: Immunometabolic role of long-chain omega-3 fatty acids in obesity-induced inflammation. Diabetes-Metab Res Rev 29: 431-445 <>
23. Galiano RD, Michael JV, Dobryanski M, Levine JP, Gurtner DC 2004: Quantitative and reproducible murine model of excisional wound healing. Wound Repair Regener 12: 485-492 <>
24. Gercek A, Yildirim O, Konya D, Bozkurt S, Ozgen S, Kilic T, Sav A, Pamir N 2007: Effects of parenteral fish-oil emulsion (Omegaven) on cutaneous wound healing in rats treated with dexamethasone. J Parenter Enter Nutr 31: 161-166 <>
25. Givens DI, Gibbs RA 2008: Current intakes of EPA and DHA in European populations and the potential of animal-derived foods to increase them. Proc Nutr Soc 67: 273-280 <>
26. Gorres KL, Raines RT 2010: Prolyl 4-hydroxylase. Crit Rev Biochem Mol Biol 45: 106-124 <>
27. Guo S, Dipietro LA 2010: Factors affecting wound healing. J Dent Res 89: 219-229 <>
28. Gundersen HJG, Bendtsen TF, Korbo L, Marcussen N, Moller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sorensen FB, Vesterby A, West MJ 1988: Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS 96: 379-394 <>
29. Gurtner GC, Werner S, Barrandon Y, Longaker MT 2008: Wound repair and regeneration. Nature 453: 314-321 <>
30. Hall JCE, Priestley JV, Perry VH Michael-Titus AT 2012: Docosahexaenoic acid, but not eicosapentaenoic acid, reduces the early inflammatory response following compression spinal cord injury in the rat. J Neurochem 121: 738-750 <>
31. Jump DB 2008: N-3 polyunsaturated fatty acid regulation of hepatic gene transcription. Curr Opin Lipidol 19: 242-247 <>
32. Komprda T 2012: Eicosapentaenoic and docosahexaenoic acids as inflammation-modulating and lipid homeostasis influencing nutraceuticals: A review. J Funct Foods 4: 25-38 <>
33. Komprda T, Ondráčková P, Vícenová M, Rozíková V, Procházková N, Levá L, Faldyna M 2018: Effect of dietary fish oil on selected inflammatory markers in pigs. Animal 12: 2098-2107 <>
34. Komprda T, Sládek Z, Škultéty O, Křížková S, Rozíková V, Němcová B, Šustrová B, Valová M 2016: Effect of dietary Schizochytrium microalga oil on selected markers of low-grade inflammation in rats. J Anim Physiol Anim Nutr 100: 1169-1178 <>
35. Kostadinova R, Wahli W, Michalik L 2005: PPARs in disease: Control mechanisms of inflammation. Curr Med Chem 12: 2413-2446 <>
36. Lin Y-K, Kuan C-Y 2010: Development of 4-hydroxyproline analysis kit and its application to collagen quantification. Food Chem 119: 1271-1277 <>
37. Liu YH, Li XY, Chen CY, Zhang HM Kang JX 2015: Omega-3 fatty acid intervention supresses lipopolysacharide-induced inflammation and weight loss in mice. Mar Drugs 13: 1026-1036 <>
38. Liu YL, Gong LM, Li DF, Feng ZY, Zhao LD Dong T 2003: Effects of fish oil on lymphocyte proliferation, cytokine production and intracellular signalling in weanling pigs. Arch Anim Nutr 57: 151-165 <>
39. McDaniel J, Belury M, Ahijevych K, Blakely W 2008: Omega-3 fatty acids effect on wound healing. Wound Rep Reg 16: 337-345 <>
40. Nakamura MT, Cheon Y, Li Y, Nara TY 2004: Mechanisms of regulation of gene expression by fatty acids. Lipids 39: 1077-1083 <>
41. Nascimento AP, Costa AM 2006: Overweight induced by high-fat diet delays rat cutaneous wound healing. Br J Nutr 96: 1069-1077 <>
42. Nguyen DT, Orgill DP, Murphy GP 2009: The pathophysiologic basis for wound healing and cutaneous regeneration. In: Orgill DP, Blanco C (Eds): Biomaterials for Treating Skin Loss. Elsevier, pp. 25-57
43. Nimptsch A, Schibur S, Ihling C, Sinz, A, Riemer T, Huster D, Schiller J 2011: Quantitative analysis of denatured collagen by collagenase digestion and subsequent MALDI-TOF mass spectrometry. Cell Tissue Res 343: 605-617 <>
44. Oliver E, McGillicudy F, Phillips C, Toomey S Roche HM 2010: The role of inflammation and macrophage accumulation in development of the obesity-induced type 2 diabetes mellitus and the possible therapeutic effects of long-chain n-3 PUFA. Proc Nutr Soc 69: 232-243 <>
45. Olson MV, Liu YC, Dangi B, Zimmer JP, Salem N, Nauroth JM 2013: Docosahexaenoic acid reduces inflammation and joint destruction in mice with collagen-induced arthritis. Inflamm Res 62: 1003-1013 <>
46. Otranto M, Do Nascimento AP, Monte-Alto-Costa A 2010: Effects of supplementation with different edible oils on cutaneous wound healing. Wound Repair Regen 18: 629-636 <>
47. Pastor-Clerigues A, Marti-Bonmati E, Milara J, Almudever P, Cortijo J 2014: Anti-inflammatory and anti-fibrotic profile of fish oil emulsions used in parenteral nutrition-associated liver disease. PLoS One 9: e115404 <>
48. Pensalfini M, Haertel E, Hopf R, Wietecha M, Werner S, Mazza E 2018: The mechanical fingerprint of murine excisional wounds. Acta Biomater 65: 226-236 <>
49. Rajendran NK, Kumar SSD, Houreld NN, Abrahamse H 2018: A review on nanoparticle based treatment for wound healing. J Drug Deliv Sci Tec 44: 421-430 <>
50. Ramanathan G, Muthukumar T, Sivagnanam UT 2017: In vivo efficiency of the collagen nanofibrous scaffold and their effect on growth factors and pro-inflammatory cytokines in wound healing. Eur J Pharmacol 814: 45-55 <>
51. Romacho T, Glosse P, Richter I, Elsen M, Schoemaker MH, van Tol EA, Eckel J 2015: Nutritional ingredients modulate adipokine secretion and inflammation in human primary adipocytes. Nutrients 7: 865-886 <>
52. Ruxton CHS, Calder PC, Reed SC, Simpson MJA 2005: The impact of LC n-3 PUFA on human health. Nutr Res Rev 18: 113-129 <>
53. Sathyanarayanan S, Muniyandi K, George E, Sivaraj D, Sasidharan SP, Thangaraj P 2017: Chemical profiling of Pterolobium hexapetalum leaves by HPLC analysis and its productive wound healing activities in rats. Biomed Pharmacother 95: 287-297 <>
54. Scardino MS, Swaim SF, Sartin EA, Hoffman CE, Oglivie GK, Hanson RA, Coolman SL, Davenport DJ 1999: The effects of omega-3 fatty acid diet enrichment on wound healing. Vet Dermatol 10: 283-290 <>
55. Schmitz G, Ecker J 2008: The opposing effects of n-3 and n-6 fatty acids. Prog Lipid Res 47: 147-155 <>
56. Seaton M, Hocking A, Gibran NS 2015: Porcine models of cutaneous wound healing. ILAR J 56: 127-138 <>
57. Serhan CN and Savill J 2005: Resolution of inflammation: the beginning programs the end. Nat Immunol 6: 1191-1197 <>
58. Serhan CN, Dalli J, Colas RA, Winkler JW, Chiang N 2015: Protectins and maresins: New pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome. Biochim Biophys Acta 1851: 397-413 <>
59. Siriwardhana N, Kalupahana NS, Cekanova M, LeMieux M, Greer B Moustaid-Moussa N 2013: Modulation of adipose tissue inflammation by bioactive food compounds. J Nutr Biochem 24: 613-623 <>
60. Turk HF, Monk JM, Fan Y-Y, Callaway ES, Weeks B, Chapkin RS 2013: Inhibitory effects of omega-3 fatty acids on injury-induced epidermal growth factor receptor transactivation contribute to delayed wound healing. Am J Physiol Cell Physiol 304: C905-C917 <>
61. van Gelder BM, Tijhuis M, Kalmijn S, Kromhout D 2007: Fish consumption, n-3 fatty acids, and subsequent 5-y cognitive decline in elderly men: the Zutphen Elderly Study. Am J Clin Nutr 85: 1142–1147 <>
62. Velnar T, Bailey T, Smrkolj V 2009: The wound healing proces: an overview of the cellular and molecular mechanisms. J Int Med Res 37: 1528-1542 <>
63. Vigerust NF, Bjørndal B, Bohov P, Brattelid T, Svardal A Berge RK 2013: Krill oil versus fish oil in modulation of inflammation and lipid metabolism in mice transgenic for TNF-α. Eur J Nutr 52: 1315-1325 <>
64. Watanabe S, Hiraoka Y, Endo S, Tanimoto Y, Tozawa Y, Watanabe Y 2015: An enzymatyic method to estimate the content of L-hydroxyproline. J Biotechnol 199: 9-16 <>
65. Weldon SM, Mullen AC Loscher CE, Hurley LA, Roche HM 2007: Docosahexaenoic acid induces an anti-inflammatory profile in lipopolysaccharide-stimulated human THP-1 macrophages more effectively than eicosapentaenoic acid. J Nutr Biochem 18: 250-258 <>
66. Yin Y, Sui C, Meng F, Ma P, Jiang Y 2017: The omega-3 polyunsaturated fatty acid docosahexaenoic acid inhibits proliferation and progression of non-small cell lung cancer cells through the reactive oxygen species-mediated inactivation of the PI3K/Akt pathway. Lipids Health Dis 16: 87 <>
67. Zárate R, el Jaber-Vazdekis N, Tejera N, Pérez JA, Rodrígues C 2017: Significance of longchain polyunsaturated fatty acids in human health. Clin Trans Med 6: 25 <>
68. Zhou J, Zhao Y, Simonenko V, Xu JJ, Liu K, Wang D, Shi J, Zhong T, Zhang L, Zeng J, Huang B, Tang S, Lu AY, Mixson AJ, Sun Y, Lu PY, Li Q 2017: Simultaneous silencing of TGF-β1 and COX-2 reduces human skin hypertrophic scar through activation of fibroblast apoptosis. Oncotarget 8: 80651-80665
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