N-3 Fatty Acid Supplementation After Burn Supports Wound Healing and Prevents Systemic Inflammation. An Experimental Study in Rats
Öz
Objective: Burn may cause hypersensitivity towards infection, systemic inflammatory response syndrome, respiratory distress syndrome and multiple organ failure. Anti-inflammatory and resistance towards infection effects of omega-3 (n-3) fatty acids was shown before. But their effect on systemic inflammation and wound healing after burn was not investigated.
Methods: Seventy Wistar albino rats were used in the study. Fourteen rats without burn composed the control group. Cutaneous burn was created on remaining 56 rats which received 50 mg/kg/day intraperitoneal ringer lactat solution in two equal amounts. Twenty-eight rats with burn received injections of n-3 1 mg/kg/day throughout the study. Rats in control group were sacrificed on day 4 and rats in treatment groups were sacrificed on days 4 and 8. Leukocyte and mast cell infiltration, epidermal and collagen thickness measurements were used in histological evaluation. White blood cell, hematocrite, total protein, albumin, fibronectin, TNFα, IL1β and IL6 levels were measured for biochemical evaluations.
Results: Elevation of leukocyte and mast cell infiltration was lower and collagen thickness was higher in n-3 receiving group on day 4. There was no difference in leukocyte infiltration on the 8th day whereas mast cell infiltration was lower and collagen thickness was higher in n-3 receiving group. Epidermal thickness was higher in n-3 receiving group on both evaluation days. White blood cell counts were higher in 8th day than 4th day groups. Total protein on 8th, IL-6 on 4th, and albumin levels on both days was lower than control.
Conclusion: N-3 fatty acids used after burn enhances wound healing and prevents systemic inflammation.
Anahtar Kelimeler
Destekleyen Kurum
Mersin Üniversitesi Tıp Fakültesi Bilimsel Araştırma Projeleri
Proje Numarası
BAP-TFCTB (ÇAÇ) 2009-4 TU
Teşekkür
Great thanks to Prof.Bahar Taşdelen, Prof.Necati Muşlu and Prof.Şakir Ünal for their support in statistical analyses, biochemical analyses and burn model application respectively.
Kaynakça
- 1. Nisancı M: Yanık Fizyopatolojisi. In: Yanıklar ve Tedavileri. Selmanpakoğlu N (Ed). Ankara, GATA Basımevi, 1998, pp 23-61
- 2. Arturson G: Pathophysiology of the burn wound and pharmacological treatment. The Rudi Hermans Lecture, 1995. Burns 1996; 22:255-74
- 3. Bjork J, Arturson G: Effect of cimetidine, hydrocortisone superoxide dismutase and catalase on the development of oedema after thermal injury. Burns Incl Therm Inj 1983; 9:249-56
- 4. Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. Jama 2001; 286:944-53
- 5. Gercek A, Yildirim O, Konya D, Bozkurt S, Ozgen S, Kilic T, Sav A, Pamir N. Effects of parenteral fish-oil emulsion (Omegaven) on cutaneous wound healing in rats treated with dexamethasone. JPEN J Parenter Enteral Nutr 2007; 31:161-6
- 6. Aksoy A, Arslan E, Basterzi Y, Unal S, Demirkan F. A new template model prepared from synthetic plaster cast for experimental burn research. Plast Reconstr Surg 2005; 115:954-5
- 7. Robinson JB, Friedman RM: Wound healing and closure. In: Selected readings in plastic surgery, Texas, 1996, pp 18-36
- 8. Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M. Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. N Engl J Med 1996; 334:1557-60
- 9. Mayser P, Grimm H, Grimminger F: n-3 fatty acids in psoriasis. Br J Nutr 2002; 87 Suppl 1:S77-82
- 10. Mayser P, Mayer K, Mahloudjian M, Benzing S, Kramer HJ, Schill WB, Seeger W, Grimminger F. A double-blind, randomized, placebo-controlled trial of n-3 versus n-6 fatty acid-based lipid infusion in atopic dermatitis. JPEN J Parenter Enteral Nutr 2002; 26:151-8
- 11. Callaway J, Schwab U, Harvima I, Halonen P, Mykkanen O, Hyvonen P, Jarvinen T. Efficacy of dietary hempseed oil in patients with atopic dermatitis. J Dermatolog Treat 2005; 16:87-94
- 12. Chen Z, Xiong Y, Lou S, Shu C. Lipid peroxidation of mitochondrial membrane induced by D1: an organic solvent extractable component isolated from a crude extract of burn eschar. Burns 1996; 22:369-75
- 13. Friedl HP, Till GO, Trentz O, Ward PA. Roles of histamine, complement and xanthine oxidase in thermal injury of skin. Am J Pathol 1989; 135:203-17
- 14. Santos FX, Arroyo C, Garcia I, Blasco R, Obispo JM, Hamann C, Espejo L. Role of mast cells in the pathogenesis of postburn inflammatory response: reactive oxygen species as mast cell stimulators. Burns 2000; 26:145-7
- 15. Jeschke MG, Herndon DN, Ebener C, Barrow RE, Jauch KW. Nutritional intervention high in vitamins, protein, amino acids, and omega3 fatty acids improves protein metabolism during the hypermetabolic state after thermal injury. Arch Surg 2001; 136:1301-6
- 16. Dale PD, Sherratt JA, Maini PK. A mathematical model for collagen fibre formation during foetal and adult dermal wound healing. Proc Biol Sci 1996; 263:653-60
- 17. Mast B, Nelson J, Krummel T. Tissue repair in the mammalian fetus. In: Wound healing: biochemical and clinical aspects.Cohen I, Diegelmann R, Lindblad W (Eds). Philadelphia, WB Sounders Co, 1992, pp73-88
- 18. Peacock E. Wound repair. Philadelphia: WB Saunders CO, 1984
- 19. Olsen L, Sherratt JA, Maini PK. A mathematical model for fibro-proliferative wound healing disorders. Bull Math Biol 1996; 58:787-808
- 20. Reinhart K, Wiegand-Lohnert C, Grimminger F, Kaul M, Withington S, Treacher D, Eckart J, Willatts S, Bouza C, Krausch D, Stockenhuber F, Eiselstein J, Daum L, and Kempeni J. Assessment of the safety and efficacy of the monoclonal anti-tumor necrosis factor antibody-fragment, MAK 195F, in patients with sepsis and septic shock: a multicenter, randomized, placebo-controlled, dose-ranging study. Crit Care Med 1996; 24:733-42
- 21. Faunce DE, Gregory MS, Kovacs EJ. Acute ethanol exposure prior to thermal injury results in decreased T-cell responses mediated in part by increased production of IL-6. Shock 1998; 10:135-40
- 22. Bellomo R. The cytokine network in the critically ill. Anaesth Intensive Care 1992; 20:288-302
- 23. de Bandt JP, Chollet-Martin S, Hernvann A, Lioret N, du Roure LD, Lim SK, Vaubourdolle M, Guechot J, Saizy R, Giboudeau J. Cytokine response to burn injury: relationship with protein metabolism. J Trauma 1994; 36:624-8
- 24. Ueyama M, Maruyama I, Osame M, Sawada Y. Marked increase in plasma interleukin-6 in burn patients. J Lab Clin Med 1992; 120:693-8
- 25. Endo S, Inada K, Yamada Y, Kasai T, Takakuwa T, Nakae H, Kikuchi M, Hoshi S, Suzuki M, Yamashita H, Yoshida M. Plasma tumour necrosis factor-alpha (TNF-alpha) levels in patients with burns. Burns 1993; 19:124-7
- 26. Agay D, Andriollo-Sanchez M, Claeyssen R, Touvard L, Denis J, Roussel AM, Chancerelle Y. Interleukin-6, TNF-alpha and interleukin-1 beta levels in blood and tissue in severely burned rats. Eur Cytokine Netw 2008; 19:1-7
- 27. Gauglitz GG, Song J, Herndon DN, Finnerty CC, Boehning D, Barral JM, Jeschke MG. Characterization of the inflammatory response during acute and post-acute phases after severe burn. Shock 2008; 30:503-7
- 28. Mester M, Carter EA, Tompkins RG, Gelfand JA, Dinarello CA, Burke JF, Clark BD. Thermal injury induces very early production of interleukin-1 alpha in the rat by mechanisms other than endotoxemia. Surgery 1994; 115:588-96
- 29. Deveci M, Eski M, Sengezer M, Kisa U. Effects of cerium nitrate bathing and prompt burn wound excision on IL-6 and TNF-alpha levels in burned rats. Burns 2000; 26:41-5
- 30. Peter FW, Schuschke DA, Barker JH, Fleishcher-Peter B, Pierangeli S, Vogt PM, Steinau HU. The effect of severe burn injury on proinflammatory cytokines and leukocyte behavior: its modulation with granulocyte colony-stimulating factor. Burns 1999; 25:477-86
- 31. Reyes R, Jr., Wu Y, Lai Q, Mrizek M, Berger J, Jimenez DF, Barone CM, Ding Y. Early inflammatory response in rat brain after peripheral thermal injury. Neurosci Lett 2006; 407:11-5
- 32. Joneidi-Jafari H, Daigeler A, Hauser J, Steinau HU, Klatte W, Fischer U, Lehnhardt M. A qualitative and quantitative analysis of protein substitution in human burn wounds. Eplasty 2009; 9:e42
- 33. Serini G, Bochaton-Piallat ML, Ropraz P, Geinoz A, Borsi L, Zardi L, Gabbiani G. The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-beta1. J Cell Biol 1998; 142:873-81
- 34. Deno DC, McCafferty MH, Saba TM, Blumenstock FA. Mechanism of acute depletion of plasma fibronectin following thermal injury in rats. Appearance of a gelatinlike ligand in plasma. J Clin Invest 1984; 73:20-34
- 35. Kwon AH, Qiu Z, Hiraon Y. Effect of plasma fibronectin on the incisional wound healing in rats. Surgery 2007; 141:254-61
Yanık Sonrası Destek Tedavisinde N-3 Yağ Asidi Kullanımı Yara İyileşmesini Destekler ve Sistemik Enflamasyonu Engeller. Sıçanlarda Yapılan Deneysel Çalışma
Öz
Amaç: Yanık enfeksiyon, sistemik enflamatuar yanıt sendromu, solunum sıkıntısı sendromu ve çoklu organ yetmezliği yatkınlığını arttırır. Omega-3 (n-3) yağ asitlerinin anti-enflamatuar ve enfeksiyona karşı direnç arttırma etkileri daha önce gösterilmiştir. Ancak yanık sonrası sistemik enflamasyon ve yara iyileşmesi üzerine etkileri bilinmemektedir.
Yöntem: Çalışmada 70 Wistar albino sıçan kullanıldı. Yanık olmayan 14 sıçan kontrol grubunu oluşturdu. Geriye kalan 56 sıçanda yanık modeli oluşturuldu ve 50 mg/kg/gün olacak şekilde periton içi ringer laktat solüsyonu eşit iki dozda verildi. Yanığı olan 28 sıçana ayrıca 1 mg/kg/gün dozunda n-3 enjekte edildi. Kontrol grubundaki sıçanlar dördüncü günde, tedavi gruplarındaki sıçanlar dört ve sekizinci günlerde sakrifiye edildi. Histolojik incelemede lökosit ve mast hücre infiltrasyonu, epidermal ve kollajen kalınlık ölçümleri değerlendirildi. Biyokimyasal incelemede beyaz küre, hematokrit, total protein, albumin, fibronektin, TNFα, IL1β ve IL6 seviyeleri ölçüldü.
Bulgular: Dördüncü günde n-3 uygulanan grupta lökosit yüksekliği ve mast hücre infiltrasyonu daha düşük, kollajen kalınlığı daha yüksek bulundu. Sekizinci günde n-3 uygulanan grupta lökosit infiltrasyonu açısından fark yok iken mast hücre infiltrasyonu daha düşük ve kollajen kalınlığı daha yüksek bulundu. N-3 uygulanan grupta her iki değerlendirme zamanında da epidermal kalınlık daha yüksekti. Sekizinci günde beyaz küre sayısı dördüncü güne göre daha yüksek bulundu. Sekizinci günde total protein, dördüncü günde IL-6 ve her iki değerlendirme zamanında albumin seviyeleri kontrol grubuna göre daha düşük bulundu.
Sonuç: Yanık sonrası n-3 yağ asidi tedavisi yara iyileşmesini destekler ve sistemik enflamasyonu önler.
Anahtar Kelimeler
Proje Numarası
BAP-TFCTB (ÇAÇ) 2009-4 TU
Kaynakça
- 1. Nisancı M: Yanık Fizyopatolojisi. In: Yanıklar ve Tedavileri. Selmanpakoğlu N (Ed). Ankara, GATA Basımevi, 1998, pp 23-61
- 2. Arturson G: Pathophysiology of the burn wound and pharmacological treatment. The Rudi Hermans Lecture, 1995. Burns 1996; 22:255-74
- 3. Bjork J, Arturson G: Effect of cimetidine, hydrocortisone superoxide dismutase and catalase on the development of oedema after thermal injury. Burns Incl Therm Inj 1983; 9:249-56
- 4. Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. Jama 2001; 286:944-53
- 5. Gercek A, Yildirim O, Konya D, Bozkurt S, Ozgen S, Kilic T, Sav A, Pamir N. Effects of parenteral fish-oil emulsion (Omegaven) on cutaneous wound healing in rats treated with dexamethasone. JPEN J Parenter Enteral Nutr 2007; 31:161-6
- 6. Aksoy A, Arslan E, Basterzi Y, Unal S, Demirkan F. A new template model prepared from synthetic plaster cast for experimental burn research. Plast Reconstr Surg 2005; 115:954-5
- 7. Robinson JB, Friedman RM: Wound healing and closure. In: Selected readings in plastic surgery, Texas, 1996, pp 18-36
- 8. Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M. Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. N Engl J Med 1996; 334:1557-60
- 9. Mayser P, Grimm H, Grimminger F: n-3 fatty acids in psoriasis. Br J Nutr 2002; 87 Suppl 1:S77-82
- 10. Mayser P, Mayer K, Mahloudjian M, Benzing S, Kramer HJ, Schill WB, Seeger W, Grimminger F. A double-blind, randomized, placebo-controlled trial of n-3 versus n-6 fatty acid-based lipid infusion in atopic dermatitis. JPEN J Parenter Enteral Nutr 2002; 26:151-8
- 11. Callaway J, Schwab U, Harvima I, Halonen P, Mykkanen O, Hyvonen P, Jarvinen T. Efficacy of dietary hempseed oil in patients with atopic dermatitis. J Dermatolog Treat 2005; 16:87-94
- 12. Chen Z, Xiong Y, Lou S, Shu C. Lipid peroxidation of mitochondrial membrane induced by D1: an organic solvent extractable component isolated from a crude extract of burn eschar. Burns 1996; 22:369-75
- 13. Friedl HP, Till GO, Trentz O, Ward PA. Roles of histamine, complement and xanthine oxidase in thermal injury of skin. Am J Pathol 1989; 135:203-17
- 14. Santos FX, Arroyo C, Garcia I, Blasco R, Obispo JM, Hamann C, Espejo L. Role of mast cells in the pathogenesis of postburn inflammatory response: reactive oxygen species as mast cell stimulators. Burns 2000; 26:145-7
- 15. Jeschke MG, Herndon DN, Ebener C, Barrow RE, Jauch KW. Nutritional intervention high in vitamins, protein, amino acids, and omega3 fatty acids improves protein metabolism during the hypermetabolic state after thermal injury. Arch Surg 2001; 136:1301-6
- 16. Dale PD, Sherratt JA, Maini PK. A mathematical model for collagen fibre formation during foetal and adult dermal wound healing. Proc Biol Sci 1996; 263:653-60
- 17. Mast B, Nelson J, Krummel T. Tissue repair in the mammalian fetus. In: Wound healing: biochemical and clinical aspects.Cohen I, Diegelmann R, Lindblad W (Eds). Philadelphia, WB Sounders Co, 1992, pp73-88
- 18. Peacock E. Wound repair. Philadelphia: WB Saunders CO, 1984
- 19. Olsen L, Sherratt JA, Maini PK. A mathematical model for fibro-proliferative wound healing disorders. Bull Math Biol 1996; 58:787-808
- 20. Reinhart K, Wiegand-Lohnert C, Grimminger F, Kaul M, Withington S, Treacher D, Eckart J, Willatts S, Bouza C, Krausch D, Stockenhuber F, Eiselstein J, Daum L, and Kempeni J. Assessment of the safety and efficacy of the monoclonal anti-tumor necrosis factor antibody-fragment, MAK 195F, in patients with sepsis and septic shock: a multicenter, randomized, placebo-controlled, dose-ranging study. Crit Care Med 1996; 24:733-42
- 21. Faunce DE, Gregory MS, Kovacs EJ. Acute ethanol exposure prior to thermal injury results in decreased T-cell responses mediated in part by increased production of IL-6. Shock 1998; 10:135-40
- 22. Bellomo R. The cytokine network in the critically ill. Anaesth Intensive Care 1992; 20:288-302
- 23. de Bandt JP, Chollet-Martin S, Hernvann A, Lioret N, du Roure LD, Lim SK, Vaubourdolle M, Guechot J, Saizy R, Giboudeau J. Cytokine response to burn injury: relationship with protein metabolism. J Trauma 1994; 36:624-8
- 24. Ueyama M, Maruyama I, Osame M, Sawada Y. Marked increase in plasma interleukin-6 in burn patients. J Lab Clin Med 1992; 120:693-8
- 25. Endo S, Inada K, Yamada Y, Kasai T, Takakuwa T, Nakae H, Kikuchi M, Hoshi S, Suzuki M, Yamashita H, Yoshida M. Plasma tumour necrosis factor-alpha (TNF-alpha) levels in patients with burns. Burns 1993; 19:124-7
- 26. Agay D, Andriollo-Sanchez M, Claeyssen R, Touvard L, Denis J, Roussel AM, Chancerelle Y. Interleukin-6, TNF-alpha and interleukin-1 beta levels in blood and tissue in severely burned rats. Eur Cytokine Netw 2008; 19:1-7
- 27. Gauglitz GG, Song J, Herndon DN, Finnerty CC, Boehning D, Barral JM, Jeschke MG. Characterization of the inflammatory response during acute and post-acute phases after severe burn. Shock 2008; 30:503-7
- 28. Mester M, Carter EA, Tompkins RG, Gelfand JA, Dinarello CA, Burke JF, Clark BD. Thermal injury induces very early production of interleukin-1 alpha in the rat by mechanisms other than endotoxemia. Surgery 1994; 115:588-96
- 29. Deveci M, Eski M, Sengezer M, Kisa U. Effects of cerium nitrate bathing and prompt burn wound excision on IL-6 and TNF-alpha levels in burned rats. Burns 2000; 26:41-5
- 30. Peter FW, Schuschke DA, Barker JH, Fleishcher-Peter B, Pierangeli S, Vogt PM, Steinau HU. The effect of severe burn injury on proinflammatory cytokines and leukocyte behavior: its modulation with granulocyte colony-stimulating factor. Burns 1999; 25:477-86
- 31. Reyes R, Jr., Wu Y, Lai Q, Mrizek M, Berger J, Jimenez DF, Barone CM, Ding Y. Early inflammatory response in rat brain after peripheral thermal injury. Neurosci Lett 2006; 407:11-5
- 32. Joneidi-Jafari H, Daigeler A, Hauser J, Steinau HU, Klatte W, Fischer U, Lehnhardt M. A qualitative and quantitative analysis of protein substitution in human burn wounds. Eplasty 2009; 9:e42
- 33. Serini G, Bochaton-Piallat ML, Ropraz P, Geinoz A, Borsi L, Zardi L, Gabbiani G. The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-beta1. J Cell Biol 1998; 142:873-81
- 34. Deno DC, McCafferty MH, Saba TM, Blumenstock FA. Mechanism of acute depletion of plasma fibronectin following thermal injury in rats. Appearance of a gelatinlike ligand in plasma. J Clin Invest 1984; 73:20-34
- 35. Kwon AH, Qiu Z, Hiraon Y. Effect of plasma fibronectin on the incisional wound healing in rats. Surgery 2007; 141:254-61
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Klinik Tıp Bilimleri |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Proje Numarası | BAP-TFCTB (ÇAÇ) 2009-4 TU |
| Erken Görünüm Tarihi | 15 Ocak 2024 |
| Yayımlanma Tarihi | 1 Ocak 2024 |
| Gönderilme Tarihi | 15 Mart 2022 |
| Yayımlandığı Sayı | Yıl 2024 Cilt: 10 Sayı: 1 |
