DOI QR코드

DOI QR Code

Effects of Topical Tamoxifen on Wound Healing of Burned Skin in Rats

  • Mehrvarz, Shaban (Trauma Research Center, Baqiyatallah University of Medical Sciences) ;
  • Ebrahimi, Ali (Trauma Research Center, Baqiyatallah University of Medical Sciences) ;
  • Sahraei, Hedayat (Department of Physiology and Biophysics, and Behavioral Sciences Research Center, Baqiyatallah University of Medical Sciences) ;
  • Bagheri, Mohammad Hasan (Trauma Research Center, Baqiyatallah University of Medical Sciences) ;
  • Fazili, Sima (Department of Pathology, Baqiyatallah University of Medical Sciences) ;
  • Manoochehry, Shahram (Trauma Research Center, Baqiyatallah University of Medical Sciences) ;
  • Rasouli, Hamid Reza (Trauma Research Center, Baqiyatallah University of Medical Sciences)
  • Received : 2016.11.13
  • Accepted : 2017.08.29
  • Published : 2017.09.15

Abstract

Background This study aimed to assess the effects of the topical application of tamoxifen on wound healing of burned skin in Wistar rats by evaluating 3 healing characteristics: fibrotic tissue thickness (FTT), scar surface area (SSA), and angiogenesis in the healed scar tissue. Methods Eighteen male Wistar rats were used in this study. A third-degree burn wound was made on the shaved animals' back, measuring $2{\times}2{\times}2cm$. In the first group, a 2% tamoxifen ointment was applied to the wound twice daily for 8 weeks. The second group received a placebo ointment during the same period. The third group did not receive any treatment and served as the control group. Results The median (interquartile range=[Q1, Q3]) FTT was 1.35 (1.15, 1.62) mm, 1.00 (0.95, 1.02) mm, and 1.25 (0.8, 1.5) mm in the control, tamoxifen, and placebo groups, respectively (P=0.069). However, the FTT in the tamoxifen group was less than in the placebo and control groups. The median angiogenesis was 3.5 (3.00, 6.25), 8.00 (6.75, 9.25), and 7.00 (5.50, 8.25) vessels per high-power field for the control, tamoxifen, and placebo groups, respectively (P=0.067). However, the median angiogenesis was higher in the tamoxifen group than in the control group. No significant difference was observed in the mean SSA between the tamoxifen group and the control group (P=0.990). Conclusions Local application of tamoxifen increased angiogenesis and decreased the FTT, with no change in the SSA in burned skin areas. These effects are expected to expedite the wound healing process, reducing contracture and preventing hypertrophic scar and keloid formation.

Keywords

References

  1. Mustoe TA, Cooter RD, Gold MH, et al. International clinical recommendations on scar management. Plast Reconstr Surg 2002;110:560-71. https://doi.org/10.1097/00006534-200208000-00031
  2. Kuhn MA, Wang X, Payne WG, et al. Tamoxifen decreases fibroblast function and downregulates TGF (beta2) in dupuytren's affected palmar fascia. J Surg Res 2002;103:146-52. https://doi.org/10.1006/jsre.2001.6350
  3. Zhao JY, Chai JK, Song HF, et al. Effect of different concentration of tamoxifen ointment on the expression of TGF-beta2 of hypertrophic scar at rabbit ears. Zhonghua Zheng Xing Wai Ke Za Zhi 2011;27:213-7.
  4. Owens LV, Cance WG, Huth JF. Retroperitoneal fibrosis treated with tamoxifen. Am Surg 1995;61:842-4.
  5. Ruffy MB, Kunnavatana SS, Koch RJ. Effects of tamoxifen on normal human dermal fibroblasts. Arch Facial Plast Surg 2006;8:329-32. https://doi.org/10.1001/archfaci.8.5.329
  6. Mousavi SR, Raaiszadeh M, Aminseresht M, et al. Evaluating tamoxifen effect in the prevention of hypertrophic scars following surgical incisions. Dermatol Surg 2010;36:665-9. https://doi.org/10.1111/j.1524-4725.2010.01526.x
  7. Carthy JM, Sundqvist A, Heldin A, et al. Tamoxifen inhibits TGF-${\beta}$-mediated activation of myofibroblasts by blocking non-smad signaling through ERK1/2. J Cell Physio 2015;230: 3084-92. https://doi.org/10.1002/jcp.25049
  8. Berman B, Maderal A, Raphael B. Keloids and hypertrophic scars: pathophysiology, classification, and treatment. Dermatol Surg 2017;43 Suppl 1:S3-18. https://doi.org/10.1097/DSS.0000000000000819
  9. Schouten HJ, Nieuwenhuis MK, van Zuijlen PP. A review on static splinting therapy to prevent burn scar contracture: do clinical and experimental data warrant its clinical application? Burns 2012;38:19-25. https://doi.org/10.1016/j.burns.2011.06.003
  10. Hu D, Hughes MA, Cherry GW. Topical tamoxifen: a potential therapeutic regime in treating excessive dermal scarring? Br J Plast Surg 1998;51:462-9. https://doi.org/10.1054/bjps.1997.0100
  11. Hu D, Zhu X, Xu M, et al. The inhibitory effect of tamoxifen on human dermal fibroblast-populated collagen lattices. Zhonghua Zheng Xing Wai Ke Za Zhi 2002;18:160-2.
  12. Pemmaraju N, Munsell MF, Hortobagyi GN, et al. Retrospective review of male breast cancer patients: analysis of tamoxifen-related side-effects. Ann Oncol 2012;23:1471-4. https://doi.org/10.1093/annonc/mdr459
  13. Sporn MB, Lippman SM. Agents for chemoprevention and their mechanism of action. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei cancer medicine. 6th ed. Hamilton: BC Decker; 2003.
  14. Leventhal D, Furr M, Reiter D. Treatment of keloids and hypertrophic scars: a meta-analysis and review of the literature. Arch Facial Plast Surg 2006;8:362-8.
  15. Zurada JM, Kriegel D, Davis IC. Topical treatments for hypertrophic scars. J Am Acad Dermatol 2006;55:1024-31. https://doi.org/10.1016/j.jaad.2006.03.022
  16. Mikulec AA, Hanasono MM, Lum J, et al. Effect of tamoxifen on transforming growth factor beta1 production by keloid and fetal fibroblasts. Arch Facial Plast Surg 2001;3:111-4. https://doi.org/10.1001/archfaci.3.2.111
  17. Foo CW, Tristani-Firouzi P. Topical modalities for treatment and prevention of postsurgical hypertrophic scars. Facial Plast Surg Clin North Am 2011;19:551-7. https://doi.org/10.1016/j.fsc.2011.06.008

Cited by

  1. Early intervention with pulse dye and CO2 ablative fractional lasers to improve cutaneous scarring post-lumpectomy: a randomized controlled trial on the impact of intervention on final cosmesis vol.34, pp.9, 2017, https://doi.org/10.1007/s10103-019-02788-3
  2. Hepatocyte Growth Factor Secreted from Human Adipose-Derived Stem Cells Inhibits Fibrosis in Hypertrophic Scar Fibroblasts vol.20, pp.None, 2017, https://doi.org/10.2174/1566524020666200106095745
  3. Comparison of the effects of pentoxifylline, simvastatin, tamoxifen, and losartan on cavernous bodies after penile fracture in rats: a stereological study vol.32, pp.3, 2017, https://doi.org/10.1038/s41443-019-0175-2