Objective: We aimed to investigate the effect of curcumin on tracheal wound healing in the anastomosis model following tracheal incision in rats.
Methods: Twenty-one healthy male Wistar Albino rats were included in the study. A horizontal incision was made between the 2nd-3th rings of the rat trachea and damage was created in the inner tracheal mucosa. Tracheal incision area was sutured and anastomosis was performed. Rats were divided into three groups. Ringer was given to the first group, corticosteroids to the 2nd group, and curcumin to the 3rd group for 28 days. The rats were sacrificed on the 28th day and the tracheal anastomosis line samples were sent for histological examination. Wound healing parameters, tracheal lumen width, wall thickness, and stenosis index were evaluated.
Results: Statistically significant difference was detected in tracheal lumen width and wall thickness in the curcumin group (p<0.05). Statistically significant differences were observed in the curcumin group in parameters of inflammation, collagen production and fibrosis. (p<0.05).
Conclusion: It is important to prevent the formation of tracheal stenosis, which is difficult to treat in clinical practice. Desired results cannot be achieved in the side-effect profile of some medical drugs used in this regard. We found the positive effect of Curcumin in the prevention of stenosis following tracheal injury.
1. Rahman NA, Fruchter O, Shitrit D, Fox BD, Kramer MR. Flexible bronchoscopic management of benign tracheal stenosis: long term follow-up of 115 patients. J Cardiothorac Surg 2010; 5: 1–5.
2. Miller TL, Zhu Y, Altman AR, Dysart K, Shaffer TH. Sequential alterations of tracheal mechanical properties in the neonatal lamb: effect of mechanical ventilation. Pediatr Pulmonol 2007; 42: 141–149.
3. Mazhar K, Gunawardana M, Webster P, Hochstim C, Koempel J, Kokot N, et al. Bacterial biofilms and increased bacterial counts are associated with airway stenosis. Otolaryngol Head Neck Surg 2014; 150: 834–840.
4. Puchalski J, Musani AI. Tracheobronchial stenosis: causes and advances in management. Clin Chest Med. 2013 Sep;34(3):557-67.
5. Gelbard A, Francis DO, Sandulache VC, Simmons JC, Donovan DT, Ongkasuwan J. Causes and consequences of adult laryngotracheal stenosis. Laryngoscope 2015;125:1137–1143.
6. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008 Jan;214(2):199-210.
7. Zhou H, Beevers CS, Huang S. The targets of curcumin. Curr Drug Targets. 2011;12(3):332-347.
8. Mirapoglu SL, Guler EM, Tok OE, Aydogdu I, Cay A, Camli MF et al. Effects of Platelet Rich Plasma and Amniotic Cell Culture Medium on Wound Healing Following Experimental Animal Tracheal Injury Model: A Comparative Study. J Craniofac Surg. 2021;32(5):1937-1941.
9. Herraka L, Ahidb S, Abouqalb R, Lescotc B, Gharbic N. Tracheal stenosis after intubation and/or tracheostomy. Egyptian Journal of Chest Diseases and Tuberculosis 2014;63:233-7.
10. Richters CD, Paauw NJ, Mayen I, van Bloois L, Metselaer JM, Storm G, et al. Administration of prednisolone phosphate-liposomes reduces wound contraction in a rat partial-thickness wound model. Wound Repair Regen. 2006;14(5):602-607.
11. Birdane L, Muluk NB, Cingi C, Burukoglu D, Fidan V, Incesulu A. Evaluation of the efficacy of curcumin in experimentally induced acute otitis media in rats. Ann Otol Rhinol Laryngol. 2014;123(5):325-32.
12. Mizokami D, Araki K, Tanaka N, Suzuki H, Tomifuji M, Yamashita T et al.Tacrolimus prevents laryngotracheal stenosis in an acute-injury rat model. Laryngoscope. 2015;125(6):E210-215.
13. House JC, Noordzij JP, Murgia B, Langmore S. Laryngeal Injury From Prolonged Intubation: a prospective analysis of contributing factors. Laryngoscope 2011;121:596-600.
15. Tsai HW, Wang PH, Tsui KH. Mesenchymal stem cell in wound healing and regeneration. J Chin Med Assoc 2017; 14. pii: S1726-4901(17)30168-5.
16. Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran: Pathologic Basis of Disease, Professional Edition. 8th ed. Philadelphia, PA: Saunders Elsevier; 2010: 139– 185.
17. George M,, Lang F,, Pasche P, Monnier P. Surgical management of laryngotracheal stenosis in adults Eur. Arch. Otorhinolaryngol. 2005; 262: 609-615.
18. Gnagi SH, Howard BE, Anderson C, Lott DG. Idiopathic subglottic and tracheal stenosis: a survey of the patient experience. Ann Otol Rhinol Laryngol. 2015;124(9):734-739.
19. Talas DU, Nayci A, Atis S, Comelekoglu U, Polat A, Bagdatoglu C et al. The effects of corticosteroids and vitamin A on the healing of tracheal anastomoses Int. J. Pediatr. Otorhinolaryngol.2003; 67 ; 109-116.
20. Talas DU, Nayci A, Polat G, Atis S, Comelekoglu U, Bagdatoglu OT et al. The effect of dexamethasone on lipid peroxidation and nitric oxide levels on the healing of tracheal anastomoses: an experimental study in rats. Pharmacol Res. 2002; 46:265–271
21. Wicke C, Halliday B, Allen D, Roche NS, Scheuenstuhl H, Spencer MM et al. Effect of steroids and retinoids on wound healing. Arch Surg.2000; 135:1265–1270
22. Shadmehr MB, Abbasidezfouli A, Farzanegan R, Pejhan S, Daneshvar A, Sheikhy K, et al. The role of systemic steroids in postintubation tracheal stenosis: a randomized clinical trial. Ann Thorac Surg 2017;103:246-53
23. Melkane AE, Matar NE, Haddad AC, Nassar MN, Almoutran HG, Rohayem Z, et al. Management of postintubation tracheal stenosis: appropriate ındications make outcome differences. Respiration 2010;79:395-401
24. Bertelsen C, Havakuk H, O’dell K, Johns M, Reder L. Serial In-Office Intralesional Steroid Injections in Airway Stenosis. JAMA Otolaryngol Head Neck Surg. 2018;144:203-210.
25. Cincik H, Gungor A, Cakmak A, Omeroglu A, Poyrazoglu E, Yildirim S et al. The effects of mitomycin C and 5-fluorouracil/triamcinolone on fibrosis/scar tissue formation secondary to subglottic trauma (experimental study). Am J Otolaryngol. 2005;26(1):45-50.
26. Pata YS, Akbaş Y, Unal M, Aydin O, Görür K, Ozcan C et al. Prevention of laryngotracheal stenosis with carnitine after tracheotomy: an experimental study on rats. Int J Pediatr Otorhinolaryngol. 2003;(8):881-8.
27. Hirshoren N, Eliashar R. Wound-healing modulation in upper airway stenosis—myths and facts. Head Neck 2009; 31: 111– 126.
28. Thangapazham RL, Sharma A, Maheshwari RK. Beneficial role of curcumin in skin diseases. Adv. Exp. Med. Biol. 2007;595:343–357.
29. Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerativee, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 2009;41:40.
30. Panchatcharam M, Miriyala S, Gayathri VS, Suguna L. curcumin improves wound healing by modulating collagen and decreasing reactive oxygen species. Mol Cell Biochem 2006;290:87-96.
31. Strimpakos AS, Sharma RA. Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal. 2008;10:511-545.
1. Rahman NA, Fruchter O, Shitrit D, Fox BD, Kramer MR. Flexible bronchoscopic management of benign tracheal stenosis: long term follow-up of 115 patients. J Cardiothorac Surg 2010; 5: 1–5.
2. Miller TL, Zhu Y, Altman AR, Dysart K, Shaffer TH. Sequential alterations of tracheal mechanical properties in the neonatal lamb: effect of mechanical ventilation. Pediatr Pulmonol 2007; 42: 141–149.
3. Mazhar K, Gunawardana M, Webster P, Hochstim C, Koempel J, Kokot N, et al. Bacterial biofilms and increased bacterial counts are associated with airway stenosis. Otolaryngol Head Neck Surg 2014; 150: 834–840.
4. Puchalski J, Musani AI. Tracheobronchial stenosis: causes and advances in management. Clin Chest Med. 2013 Sep;34(3):557-67.
5. Gelbard A, Francis DO, Sandulache VC, Simmons JC, Donovan DT, Ongkasuwan J. Causes and consequences of adult laryngotracheal stenosis. Laryngoscope 2015;125:1137–1143.
6. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008 Jan;214(2):199-210.
7. Zhou H, Beevers CS, Huang S. The targets of curcumin. Curr Drug Targets. 2011;12(3):332-347.
8. Mirapoglu SL, Guler EM, Tok OE, Aydogdu I, Cay A, Camli MF et al. Effects of Platelet Rich Plasma and Amniotic Cell Culture Medium on Wound Healing Following Experimental Animal Tracheal Injury Model: A Comparative Study. J Craniofac Surg. 2021;32(5):1937-1941.
9. Herraka L, Ahidb S, Abouqalb R, Lescotc B, Gharbic N. Tracheal stenosis after intubation and/or tracheostomy. Egyptian Journal of Chest Diseases and Tuberculosis 2014;63:233-7.
10. Richters CD, Paauw NJ, Mayen I, van Bloois L, Metselaer JM, Storm G, et al. Administration of prednisolone phosphate-liposomes reduces wound contraction in a rat partial-thickness wound model. Wound Repair Regen. 2006;14(5):602-607.
11. Birdane L, Muluk NB, Cingi C, Burukoglu D, Fidan V, Incesulu A. Evaluation of the efficacy of curcumin in experimentally induced acute otitis media in rats. Ann Otol Rhinol Laryngol. 2014;123(5):325-32.
12. Mizokami D, Araki K, Tanaka N, Suzuki H, Tomifuji M, Yamashita T et al.Tacrolimus prevents laryngotracheal stenosis in an acute-injury rat model. Laryngoscope. 2015;125(6):E210-215.
13. House JC, Noordzij JP, Murgia B, Langmore S. Laryngeal Injury From Prolonged Intubation: a prospective analysis of contributing factors. Laryngoscope 2011;121:596-600.
15. Tsai HW, Wang PH, Tsui KH. Mesenchymal stem cell in wound healing and regeneration. J Chin Med Assoc 2017; 14. pii: S1726-4901(17)30168-5.
16. Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran: Pathologic Basis of Disease, Professional Edition. 8th ed. Philadelphia, PA: Saunders Elsevier; 2010: 139– 185.
17. George M,, Lang F,, Pasche P, Monnier P. Surgical management of laryngotracheal stenosis in adults Eur. Arch. Otorhinolaryngol. 2005; 262: 609-615.
18. Gnagi SH, Howard BE, Anderson C, Lott DG. Idiopathic subglottic and tracheal stenosis: a survey of the patient experience. Ann Otol Rhinol Laryngol. 2015;124(9):734-739.
19. Talas DU, Nayci A, Atis S, Comelekoglu U, Polat A, Bagdatoglu C et al. The effects of corticosteroids and vitamin A on the healing of tracheal anastomoses Int. J. Pediatr. Otorhinolaryngol.2003; 67 ; 109-116.
20. Talas DU, Nayci A, Polat G, Atis S, Comelekoglu U, Bagdatoglu OT et al. The effect of dexamethasone on lipid peroxidation and nitric oxide levels on the healing of tracheal anastomoses: an experimental study in rats. Pharmacol Res. 2002; 46:265–271
21. Wicke C, Halliday B, Allen D, Roche NS, Scheuenstuhl H, Spencer MM et al. Effect of steroids and retinoids on wound healing. Arch Surg.2000; 135:1265–1270
22. Shadmehr MB, Abbasidezfouli A, Farzanegan R, Pejhan S, Daneshvar A, Sheikhy K, et al. The role of systemic steroids in postintubation tracheal stenosis: a randomized clinical trial. Ann Thorac Surg 2017;103:246-53
23. Melkane AE, Matar NE, Haddad AC, Nassar MN, Almoutran HG, Rohayem Z, et al. Management of postintubation tracheal stenosis: appropriate ındications make outcome differences. Respiration 2010;79:395-401
24. Bertelsen C, Havakuk H, O’dell K, Johns M, Reder L. Serial In-Office Intralesional Steroid Injections in Airway Stenosis. JAMA Otolaryngol Head Neck Surg. 2018;144:203-210.
25. Cincik H, Gungor A, Cakmak A, Omeroglu A, Poyrazoglu E, Yildirim S et al. The effects of mitomycin C and 5-fluorouracil/triamcinolone on fibrosis/scar tissue formation secondary to subglottic trauma (experimental study). Am J Otolaryngol. 2005;26(1):45-50.
26. Pata YS, Akbaş Y, Unal M, Aydin O, Görür K, Ozcan C et al. Prevention of laryngotracheal stenosis with carnitine after tracheotomy: an experimental study on rats. Int J Pediatr Otorhinolaryngol. 2003;(8):881-8.
27. Hirshoren N, Eliashar R. Wound-healing modulation in upper airway stenosis—myths and facts. Head Neck 2009; 31: 111– 126.
28. Thangapazham RL, Sharma A, Maheshwari RK. Beneficial role of curcumin in skin diseases. Adv. Exp. Med. Biol. 2007;595:343–357.
29. Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerativee, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 2009;41:40.
30. Panchatcharam M, Miriyala S, Gayathri VS, Suguna L. curcumin improves wound healing by modulating collagen and decreasing reactive oxygen species. Mol Cell Biochem 2006;290:87-96.
31. Strimpakos AS, Sharma RA. Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal. 2008;10:511-545.
Yıldız MG, Kılınç E, Yalçın N, Çakan D, Orhan İ, Kara İ, Yoldaş A, Doğaner A. Effectıveness of Curcumın on Tracheal Anastomosıs Created in the Rat Model. Mid Blac Sea J Health Sci. 2023;9(2):363-75.