The Effect of Injection of Steroid and 5-Fluorouracil on Hypertrophic Scars of Rabbit

가토의 비후성 반흔에서 스테로이드와 5-플루오르우라실 투여 효과

  • Kim, Kyung-Rak (Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University) ;
  • Ryu, Sun-Youl (Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University)
  • 김경락 (전남대학교 치의학전문대학원 구강악안면외과학교실) ;
  • 유선열 (전남대학교 치의학전문대학원 구강악안면외과학교실)
  • Received : 2011.04.05
  • Accepted : 2011.05.09
  • Published : 2011.05.31

Abstract

Purpose: This study was to evaluate the synergistic effects of combined therapy of steroid and anti-neoplastic drug injection on hypertrophic scars in a rabbit model. Methods: Adult male white rabbits weighing about 2.5 kg were used. After full thickness wounding (about 6 mm) over the ventral surface of each ear sized was made, either saline (control group), triamcinolone, 5-fluoruracil, and mixture of triamcinolone and 5-fluoruracil were injected once 16 days after the wound was made. Rabbits were sacrificed 2, 4 and 8 weeks after injection, and tissue specimens were prepared for histologic and histomorphometric examinations. Results: With the combined injection of triamcinolone and 5-fluoruracil, collagen fiber thickness was arranged in a somewhat irregular manner 2 weeks after injection. After 4 weeks, blood vessels and inflammatory cells were decreased, and collagen fibers were arranged in an almost parallel manner. By 8 weeks, almost same amount of connective tissue compared with adjacent normal tissue was observed. Conclusion: These results indicated that combined injection of triamcinolone and 5-fluoruracil reduced the amount of hypertrophic scars by inhibition of fibroblasts and inflammatory cells. Therefore, combined injection of triamcinolone and 5-fluoruracil is a more potent and effective treatment of hypertrophic scars compared with the single injection of either triamcinolone or 5-fluorouracil.

Keywords

References

  1. Ladin DA, Garner WL, Smith DJ Jr. Excessive scarring as a consequence of healing. Wound Repair Regen 1995;3:6-14. https://doi.org/10.1046/j.1524-475X.1995.30106.x
  2. Niessen FB, Spauwen PH, Schalkwijk J, Kon M. On the nature of hypertrophic scars and keloids: a review. Plast Reconstr Surg 1999;104:1435-58. https://doi.org/10.1097/00006534-199910000-00031
  3. Haurani MJ, Foreman K, Yang JJ, Siddiqui A. 5-Fluorouracil treatment of problematic scars. Plast Reconstr Surg 2009;123:139-48; discussion 149-51. https://doi.org/10.1097/PRS.0b013e3181904d1b
  4. Huang JS, Wang YH, Ling TY, Chuang SS, Johnson FE, Huang SS. Synthetic TGF-beta antagonist accelerates wound healing and reduces scarring. FASEB J 2002;16:1269-70.
  5. Muir IF. On the nature of keloid and hypertrophic scars. Br J Plast Surg 1990;43:61-9. https://doi.org/10.1016/0007-1226(90)90046-3
  6. Thomas DW, Hopkinson I, Harding KG, Shepherd JP. The pathogenesis of hypertrophic/keloid scarring. Int J Oral Maxillofac Surg 1994;23:232-6. https://doi.org/10.1016/S0901-5027(05)80377-7
  7. Sherris DA, Larrabee WF Jr, Murakami CS. Management of scar contractures, hypertrophic scars, and keloids. Otolaryngol Clin North Am 1995;28:1057-68.
  8. Baker BL, Whitaker WL. Interference with wound healing by the local action of adrenocortical steroids. Endocrinology 1950;46:544-51. https://doi.org/10.1210/endo-46-6-544
  9. Griswold ML Jr. Effects of adrenal cortical preparations on scar hypertrophy. Plast Reconstr Surg (1946) 1954;13:454-61. https://doi.org/10.1097/00006534-195406000-00005
  10. Murray RD. Kenalog and the treatment of hypertrophied scars and keloids in Negroes and whites. Plast Reconstr Surg 1963;31:275-80. https://doi.org/10.1097/00006534-196303000-00007
  11. Ketchum LD, Smith J, Robinson DW, Masters FW. The treatment of hypertrophic scar, keloid and scar contracture by triamcinolone acetonide. Plast Reconstr Surg 1966;38:209-18. https://doi.org/10.1097/00006534-196609000-00005
  12. Bouchard J, May RM. Stathmokinetic test applied to the study of the physiology of mitosis in normal, cicatricial or cancerous epidermis. Arch Sci Physiolo 1967;21:153-83.
  13. Shridharani SM, Magarakis M, Manson PN, Singh NK, Basdag B, Rosson GD. The emerging role of antineoplastic agents in the treatment of keloids and hypertrophic scars: a review. Ann Plast Surg 2010;64:355-61. https://doi.org/10.1097/SAP.0b013e3181afaab0
  14. Manuskiatti W, Fitzpatrick RE. Treatment response of keloidal and hypertrophic sternotomy scars: comparison among intralesional corticosteroid, 5-fluorouracil, and 585-nm flashlamp-pumped pulsed-dye laser treatments. Arch Dermatol 2002;138:1149-55. https://doi.org/10.1001/archderm.138.9.1149
  15. Morris DE, Wu L, Zhao LL, et al. Acute and chronic animal models for excessive dermal scarring: quantitative studies. Plast Reconstr Surg 1997;100:674-81. https://doi.org/10.1097/00006534-199709000-00021
  16. Goldan O, Weissman O, Regev E, Haik J, Winkler E. Treatment of postdermabrasion facial hypertrophic and keloid scars with intralesional 5-Fluorouracil injections. Aesthetic Plast Surg 2008;32:389-92. https://doi.org/10.1007/s00266-007-9109-3
  17. Reid RR, Roy N, Mogford JE, Zimmerman H, Lee C, Mustoe TA. Reduction of hypertrophic scar via retroviral delivery of a dominant negative TGF-beta receptor II. J Plast Reconstr Aesthet Surg 2007;60:64-72; discussion 73-4. https://doi.org/10.1016/j.bjps.2005.12.026
  18. Dockery GL. Hypertrophic and keloid scars. J Am Podiatr Med Assoc 1995;85:57-60.
  19. Grieco MH, Cushman P Jr. Adrenal glucocorticoids after twenty years: a review of their slinically relevant consequences. J Chronic Dis 1970;22:637-41. https://doi.org/10.1016/0021-9681(70)90078-0
  20. Robb EC, Waymack JP, Warden GD, Nathan P, Alexander JW. A new model for studying the development of human hypertrophic burn scar formation. J Burn Care Rehabil 1987;8:371-5. https://doi.org/10.1097/00004630-198709000-00006
  21. Kischer CW, Pindur J, Shetlar MR, Shetlar CL. Implants of hypertrophic scars and keloids into the nude (athymic) mouse: viability and morphology. J Trauma 1989;29:672-7. https://doi.org/10.1097/00005373-198905000-00023
  22. Goss RJ, Grimes LN. Epidermal downgrowths in regenerating rabbit ear holes. J Morphol 1975;146:533-42. https://doi.org/10.1002/jmor.1051460408
  23. Mustoe TA, Pierce GF, Morishima C, Deuel TF. Growth factor-induced acceleration of tissue repair through direct and inductive activities in a rabbit dermal ulcer model. J Clin Invest 1991;87:694-703. https://doi.org/10.1172/JCI115048
  24. Fitzpatrick RE. Treatment of inflamed hypertrophic scars using intralesional 5-FU. Dermatol Surg 1999;25:224-32. https://doi.org/10.1046/j.1524-4725.1999.08165.x
  25. Apikian M, Goodman G. Intralesional 5-fluorouracil in the treatment of keloid scars. Australas J Dermatol 2004;45:140-3. https://doi.org/10.1111/j.1440-0960.2004.00072.x