Effects of phenytoin injection on vocal cord healing after mechanical trauma: An experimental study
Effects of phenytoin injection on vocal cord healing after mechanical trauma: An experimental study
Background/aim: Phenytoin is an anticonvulsant drug which causes fibroblast proliferation, collagen synthesis, and an increase inepidermal growth factor. Therefore, the aim of the present study is to evaluate the effect of phenytoin injection on the wound healingprocess in rats with vocal cord injury by histopathological methods.Materials and methods: The vocal cords of 10 albino Wistar rats were damaged bilaterally; the left vocal cord was kept as the controlgroup. Phenytoin was injected in the right vocal cord. Ten rats were sacrificed. The thickness of the lamina propria and density of thefibroblast and collagen were evaluated histopathologically.Results: Thickness of the lamina propria was 18.0 ± 7.1 µm in the control group, 65.5 ± 10.7 µm in the phenytoin group. The density offibroblast and collagen were statistically lower in the control group compared the phenytoin group (P < 0.05).Conclusion: Phenytoin injection in rats after vocal cord injury significantly increased the thickness of the lamina propria and density offibroblast and regular and mature collagen in the lamina propria. The findings in our study provide a feasible scientific view for addingphenytoin treatment to vocal cord surgeries in otolaryngology practice, but further studies are needed in order to evaluate the use ofphenytoin in preventing the formation of scar tissue and possible effects on vocal cord vibration in humans after vocal cord injury.
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- 1. Ohno S, Hirano S, Kanemaru S, Kitani Y, Kojima T et al.
Transforming growth factor β3 for the prevention of vocal
fold scarring. Laryngoscope 2012; 122: 583-589. doi: 10.1002/
lary.22389
- 2. Wingstrand VL, Grønhøj Larsen C, Jensen DH, Bork K,
Sebbesen L et al. Mesenchymal stem cell therapy for the
treatment of vocal fold scarring: a systematic review of
preclinical studies. PLoS One 2016 15; 11: e0162349. doi:
10.1371/journal.pone.0162349
- 3. Cedervall J, Ahrlund-Richter L, Svensson B, Forsgren K,
Maurer FH et al. Injection of embryonic stem cells into
scarred rabbit vocal folds enhances healing and improves
viscoelasticity: short-term results. Laryngoscope 2007; 117:
2075-2081. doi: 10.1097/MLG.0b013e3181379c7c
- 4. Hertegård S, Cedervall J, Svensson B, Forsberg K, Maurer FH et
al. Viscoelastic and histologic properties in scarred rabbit vocal
folds after mesenchymal stem cell injection. Laryngoscope
2006; 116: 1248-1254
- 5. Hu R, Xu W, Ling W, Wang Q, Wu Y et al. Characterization
of extracellular matrix proteins during wound healing in the
lamina propria of vocal fold in a canine model: A long-term
and consecutive study. Acta Histochemica 2014; 116: 730-735.
doi: 10.1016/j.acthis.2013.12.014
- 6. Tateya T, Tateya I, Sohn JH, Bless DM. Histological study
of acute vocal fold injury in a rat model. Annals of Otology,
Rhinology, and Laryngology. 2006; 115: 285-292. doi:
10.1177/000348940611500406
- 7. Sataloff RT. Autologous fat implantation for vocal cord scar.
Current Opinion in Otolaryngology & Head and Neck Surgery
2010; 18: 503-506
- 8. Hirano S, Bless DM, Rousseau B, Wlham N, Montequin D
et al. Prevention of vocal fold scarring by topical injection of
hepatocyte growth factor in a rabbit model. Laryngoscope
2004 114: 548-556. doi: 10.1097/00005537-200403000-00030
- 9. Bless DM, Welham NV. Characterization of vocal fold scar
formation, prophylaxis, and treatment using animal models.
Current Opinion in Otolaryngology & Head and Neck Surgery.
2010; 18: 481-486. doi: 10.1097/MOO.0b013e3283407d87
- 10. Woo SH, Jeong HS, Kim JP, Koh EH, Lee SU et al. Favorable
vocal fold wound healing induced by platelet-rich plasma
injection. Clinical and Experimental Otorhinolaryngology
2014; 7: 47-52. doi: 10.3342/ceo.2014.7.1.47.
- 11. Bhatia A, Prakash S. Topical phenytoin for wound healing.
Dermatol Online Journal. 2004 15;10: 5.
- 12. Mirnezami M, Rahimi H, Fakhar HE, Rezaei K. The role of
topical estrogen, phenytoin, and silver sulfadiazine in time to
wound healing in rats. Ostomy Wound Management 2018; 64:
30-34.
- 13. Pereira CA, Alchorne Ade O. Assessment of the effect of
phenytoin on cutaneous healing from excision of melanocytic
nevi on the face and on the back. BMC Dermatology 2010;
24(10): 7. doi: 10.1186/1471-5945-10-7
- 14. Tateya T, Tateya I, Sohn JH, Bless DM. Histologic
characterization of rat vocal fold scarring. Annals of Otology,
Rhinology, and Laryngology 2005 Mar; 114: 183-191. doi
10.1177/000348940511400303
- 15. Yildiz M, Yigit O, Sünter AV, Edizer DT, Dursun N et al.
Effects of intracordal estradiol and dexamethasone injection
on wound healing in vocal fold injuries. Journal of Voice 2018.
doi: 10. 1016/j.jvoice.2018.01.020
- 16. Suzuki R, Kawai Y, Tsuji T, Hiwatashi N, Kishimoto Y et al.
Prevention of vocal fold scarring by local application of basic
fibroblast growth factor in a rat vocal fold injury model.
Laryngoscope 2017; 127: 67-74. doi: 10.1002/lary.26138
- 17. Shaw J, Hughes CM, Lagan KM, Bell PM. The clinical effect
of topical phenytoin on wound healing: a systematic review.
British Journal of Dermatology 2007; 157: 997-1004. doi:
10.1111/j.1365-2133.2007.08160.x
- 18. Turan M, Saraydyn SU, Bulut HE, Elagöz S, Cetinkaya O et
al. Do vascular endothelial growth factor and basic fibroblast
growth factor promote phenytoin’s wound healing effect in
rat? An immunohistochemical and histopathologic study.
Dermatologic Surgery 2004; 30: 1303-1309. doi: 10.1111/j.1524-
4725.2004.30404.x
- 19. Şimşek G, Ciftci O, Karadag N, Karatas E, Kizilay A. Effects
of topical phenytoin on nasal wound healing after mechanical
trauma: An experimental study. Laryngoscope 2014; 124: 449-
454. doi: 10.1002/lary.24811
- 20. Inchingolo F, Vermesan D, Inchingolo AD, Malcangi G,
Santacroce L et al. Bedsores successfully treated with topical
phenytoin. Acta Biomedica 2017; 88: 45-48. doi: 10.23750/
abm.v88i1.5794
- 21. Hao XY, Li HL, Su H, Cai H, Guo TK et al. Topical phenytoin
for treating pressure ulcers. Cochrane Database Systematic
Review 2017; 2: CD008251. doi: 10.1002/14651858.CD008251.
pub2
- 22. Habibipour S, Oswald TM, Zhang F, Joshi P, Zhou XC et al.
Effect of sodium diphenylhydantoin on skin wound healing
in rats. Plastic and Reconstructive Surgery 2003; 112: 1620-
1627. doi: 10.1097/01.PRS.0000086773.96319.DA
- 23. Valerie A, Vassiliki K, Irini M, Nikolaos P, Karampela E et al.
Adipose-derived mesenchymal stem cells in the regeneration
of vocal folds: a study on a chronic vocal fold scar. Stem Cells
International. 2016; 9010279. doi: 10.1155/2016/9010279
- 24. Svensson B, Nagubothu SR, Cedervall J, Chan RW, Le Blanc
K et al. Injection of human mesenchymal stem cells improves
healing of vocal folds after scar excision: a xenograft analysis.
Laryngoscope 2011; 121: 2185-2190. doi: 10.1002/lary.22143