Investigation of Ototoxicity of Intratympanic 5-fluorouracil in Rats

Year 2022, , 115 - 120, 24.01.2023

Meltem Demirdağ Çevikkan , Asım Aslan , Elgin Türköz Uluer , Damla Demirkaya Tas

https://doi.org/10.26650/Tr-ENT.2022.1216068

Abstract

Objective: Although 5-fluorouracil is beneficial in treating cholesteatoma in people, it is unknown if this drug harms the inner ear. We are planning to contribute to the literature by investigating the effects of the intratympanic administration of 5-fluorouracil solution form to the middle ear on the inner ear in rats. Materials and Methods: The study was conducted on 11 Wistar albino male rats: a positive control group was treated with amikacin, a study group was treated with 5-FU, and a negative control group received no treatment. One week after intratympanic drug administration, the rats were sacrificed, and ototoxicity was histopathologically examined by light microscopy and TUNEL (Terminal deoxynucleotidyl transferasemediated dUTP Nick End Labeling) method. Results: There was a significant difference between the two groups treated with amikacin and 5-fluorouracil in terms of apoptosis (p<0.05). The difference in stria vascularis thicknesses was significant between the amikacin group and the 5-fluorouracil group and the negative control group (p<0.05). Conclusion: The intratympanic administration of 5-fluorouracil to rats did not have any ototoxic effects, according to the results of the histological analysis that looked at apoptosis.

Keywords

5-fluorouracil, ototoxicity, intratympanic injection, animal model

Supporting Institution

Scientific Research Projects Coordination Unit of Manisa Celal Bayar University

Project Number

109-2009

Thanks

The authors would like to thank the people that work at experimental animals laboratory.

References

• 1. Olszewska E, Chodynicki S, Chyczewski L. Apoptosis in the pathogenesis of cholesteatoma in adults. Eur Arch Otorhinolaryngol 2006; 263:409-13. google scholar
• 2. Sheehy JL, Brackmann DE, Graham MD. Cholesteatoma Surgery: Residual and Recurrent Disease. Ann Otol Rhinol Laryngol 1977;86(4):451-62 google scholar
• 3. Tomlin J, Chang D, McCutcheon B, and Harris J. Surgical technique and recurrence in cholesteatoma: a meta-analysis. Audiol Neurotol 2013;18(3):135-42. google scholar
• 4. Smith MF. The topikal use of 5-fluorouracil in the ear in the management of cholesteatoma and excessive mucous secretion. Laryngoscope 1985;95(10):1202-3. google scholar
• 5. Iwanaga T, Tanaka F, Tsukasaki N, Terakado M, Kaieda S, Takasaki K, et al. Does topical application of 5-fluorouracil ointment influence inner ear function? Otolaryngol Head Neck Surg 2006:134;961-5. google scholar
• 6. Ceilley RI. Mechanisms of action of topical 5-fluorouracil: Review and implications for the treatment of dermatological disorders. J Dermatolog Treat 2010;23(2):83-9. google scholar
• 7. Erlanger M, Martz G, Ott F, Storck H, Rieder J, Kessler S. Cutaneous absorption and urinary excretion of 5-fluorouracil ointment applicated in an ointment to healthy and diseased human skin. Dermatologica 1970;140 (suppl I):7-14. google scholar
• 8. Takahashi H, Funabiki K, Hasebe S, Yamamoto TF, Kaieda S, Iwanaga T, et al. Clinical efficacy of 5-fluorouracil (5-FU) topical cream for treatment of cholesteatoma. Auris Nasus Larynx 2005:32(4);353-7. google scholar
• 9. Sala DT. Topical applications of 5-fluorouracil in the medical treatment of cholesteatoma of the middle ear. Ear Nose Throat J 1994;73(6):412-4. google scholar
• 10. Salt AN, Plontke SK. Principles of local drug delivery to the inner ear. Audiol Neurootol 2009;14:350-60. google scholar
• 11. Morizono T, Paparella MM, Juhn SK. Ototoxicity of propylene glycol in experimental animals. Am J Otolaryngol 1980;1(5):393-9. google scholar
• 12. Wright CG, Bird LL, Meyerhoff WL. Effect of 5-fluorouracil in cholesteatoma development in an animal model. Am J Otolaryngol 1991;12(3):133-8. google scholar
• 13. Elmore S. Apoptosis: A Review of Programmed Cell Death. Toxicol Pathol 2007;35(4):495-516. google scholar
• 14. Salcan İ, Dilber M, Bayram R, Süleyman E, Yazıcı GN, Çoban A, Süleyman H. Effect of Rutin on Gentamicin-Induced Ototoxicity in Rats: A Biochemical and Histopathological Examination. ENTUpdates 2021;11(1):8-13. google scholar
• 15. Ganesan P, Schmiedge J, Manchaiah V, Swapna S, Dhandayutham S, Kothandaraman P P. Ototoxicity: A Challenge in Diagnosis and Treatment. J Audiol Otol 2018;22(2):59-68. google scholar