Fatmanur UYSAL, Selim ERBEK, Seyra ERBEK, Belde ÇULHAOĞLU

Ratlarda takrolimusun iç kulak üzerindeki etkisi

Amaç: İmmünosupresif bir ajan olan takrolimus, özellikle organ nakli sonrası kullanılmaktadır. Takrolimusun bazı çalışmalarda işitsel sistem üzerinde koruyucu, bazı çalışmalarda ise olumsuz etkileri olduğu ileri sürülmüştür. Çalışmamızın amacı ratlarda takrolimusun iç kulağa etkisini araştırmaktır. Gereç ve Yöntem: Çalışmamıza 20 adet, ortalama 250-350gram ağırlığında, sağlıklı Spraquey Downey erkek ratlar dahil edildi. Birinci grup 1mg/kg takrolimus (n=7), ikinci grup 0.1mg/kg takrolimus (n=7) verilen ratlar ve üçüncü grup ise (n=6) ilaç verilmeyen kontrol grubudur. Deneye başlamadan önce DPOAE ile tüm ratların ilk ölçümleri yapıldı. Daha sonra 30 gün boyunca 1. ve 2. gruba belirlenen dozda takrolimus ilacı gavaj yöntemi günde bir kez uygulandı. Son ölçüm ise 30. günde tekrarlandı. Bulgular: İlk ölçüm sonuçlarına göre tüm ratlarda emisyon elde edilmiş ve yanıtların benzer özelliklere sahip olduğu saptanmıştır. Aynı şekilde gruplara yapılan son ölçümlerdeki SNR değerleri arasındaki fark istatistiksel olarak anlamlılık göstermedi. Sonuç: Yapılan tüm DPOAE ölçümlerinden yola çıkarak takrolimusun en azından verilen doz ve sürede ratlarda işitme sistemi üzerinde toksik bir etkisinin olmadığı söylenebilir. Bu çalışma farklı doz ve sürelerde verilen takrolimus ile başka çalışmalara öncü olabilir

Anahtar Kelimeler:

Ototoksisite, distorsiyon ürünü ototakustik emisyon, takrolimus, işitme kaybı

Effect of tacrolimus in the inner ear of rats

Purpose: Tacrolimus, an immunosuppressive agent, is used especially after organ transplantation. It has been asserted that tacrolimus has protective effects on the auditory system in some studies while it has negative effects in other studies. The purpose of our study is to investigate the effect of tacrolimus on the inner ear of the rats. Materials and Methods: 20 healthy Sprague Downey male rats weighing 250-350 grams were included in our study. The first group of rats were given 1mg/kg tacrolimus (n:7), the second group of rats were given 0.1 mg/kg tacrolimus (n:7), and the third group (n:6) was the non-administered control group. The first measurements of all rats were taken with distortion-product otoacoustic emission before starting the experiment. Then, tacrolimus drug was administered by gavage method to the 1st and 2nd groups along 30 days. The last measurement was repeated on the 30th day. Results: According to the results of the first measurements, emission was obtained in all rats and the responses were found to have similar characteristics. Similarly, the difference between the signal noise rate values in the last measurements taken from the groups did not show any statistical significance. Conclusions: Based on the distortion-product otoacoustic emission measurements, it can be said that Tacrolimus does not have ototoxic effects on the auditory system of rats considering the administered dosage and time.

Keywords:

Distortion-product otoacoustic emission, hearing loss, ototoxicity, tacrolimus,

PDF

___

1. Bisht M, Bist S. Ototoxicity: the hidden menace. Indian J Otolaryngol Head Neck Surg. 2011;63:255-9.
2. Hatzopoulos S, Di Stefano M, Albertin A, Martini A. Evaluation of cisplatin ototoxicity in a rat animal model. Ann N Y Acad Sci. 1999;884:211-5.
3. Akbaba D. Evaluation of immunosuppressive blood drug level monitoring and the relationship between the test results obtained and biochemical parameters (Master thesis). İstanbul, Sağlık Bilimleri University. 2009.
4. Mok CC, Tong KH, To CH, Siu YP, Au TC. Tacrolimus for induction therapy of diffuse proliferative lupus nephritis: an open-labeled pilot study. Kidney Int. 2005;68:813-7.
5. Yarosh DB, Pena AV, Nay SL, Canning MT, Brown DA. Calcineurin inhibitors decrease DNA repair and apoptosis in human keratinocytes following ultraviolet B irradiation. J Invest Dermatol. 2005;125:1020-5.
6. Bas E, Martinez-Soriano F, Láinez JM, Marco J. An experimental comparative study of dexamethasone, melatonin and tacrolimus in noise-induced hearing loss. Acta Otolaryngol. 2009;129:385-9.
7. Delmas J, Varoquaux A, Troude L, Salburgo F, Lavieille J-P, Montava M. Incidental effect of longterm tacrolimus treatment on sporadic vestibular schwannoma volume shrinkage and clinical improvement. Otol Neurotol. 2020;41:89-3.
8. Gulleroglu K, Baskin E, Aydin E, Ozluoglu L, Moray G, Haberal M. Hearing status in pediatric renal transplant recipients. Exp Clin Transplant. 2015;13:324-8.
9. Minami SB, Yamashita D, Schacht J, Miller JM. Calcineurin activation contributes to noise‐induced hearing loss. J Neurosci Res. 2004;78:383-2.
10. Norman K, Bonatti H, Dickson RC, Aranda‐Michel J. Sudden hearing loss associated with tacrolimus in a liver transplant recipient. Transplant International. 2006;19:601-3.
11. Rifai K, Klempnauer J, Manns M, Strassburg CP. Sudden hearing loss associated with high levels of calcineurin inhibitors after liver transplantation. Transplantationsmedizin. 2006;18:33-5.
12. Rifai K, Kirchner GI, Bahr MJ, Cantz T, Rosenau J, Nashan B et al. A new side effect of immunosuppression: high incidence of hearing impairment after liver transplantation. Liver Transpl. 2006;12:411-5.
13. Rifai K, Bahr M, Cantz T, Klempnauer J, Manns M, Strassburg C et al. Severe hearing loss after liver transplantation. Transplantation Proc. 2005;37,1918- 9.
14. Fortes ME, Marroni CA, Coser PL, de los Santos CA. Audiometric changes in patients undergoing liver transplantation using distinct immunosuppressive protocols. Liver Transpl. 2008;14:509-1.
15. Uemaetomari I, Tabuchi K, Hoshino T, Hara A. Protective effect of calcineurin inhibitors on acoustic injury of the cochlea. Hearing Res. 2005;209:86-0.
16. Lakshmi B, Vidya B, Reddy M, Kumar A, Ram R, Kumar V. Sensorineural deafness following tacrolimus use. Exp Clin Transplant. 2020;18:110-1.