Özlem ÇELEBİ ERDİVANLI, Sedat AYDIN, Emin AYDURAN, Zeynep Alev SARISOY, Mustafa PAKSOY, Arif ŞANLI

Th e protective eff ect of dexamethasone and lactate against cisplatin-induced ototoxicity

Amaç: Sisplatin ototoksisitesinde intratimpanik deksametazon ve laktatın koruyucu etkinlikleri karşılaştırıldı. Yöntem ve gereç: Otuz Wistar cinsi sıçan rastgele dört guruba ayrıldı. Sıçanlar intraperitonal ketamine hydrochloride (50 mg/kg) ve xylazine (7.5 mg/kg) ile sedatize edildikten sonra, Bütün hayvanların uygulamalar öncesinde ABR (Auditory brainstem response) ile 4, 8, 12 ve 16 kHz’de klik ve “tone-pips” uyaranlarla bazal işitme eşikleri saptandı. Oditör eşikler saptandıktan sonra, sıçanlara aşağıdaki sırayla ilaçlar uygulandı: 1. Grup (n: 6) intratimpanik % 0,9 salin(NaCl) solusyonu; 2. Grup (n: 8), yalnızca intraperitoneal sisplatin (20 mg/kg); 3. Grup (n: 8) intraperitoneal sisplatin ile birlikte intratimpanik dekzametazon (0.1-0.3 mL) ve 4. Grup (n: 8) 20 mg/kg sisplatin uygulamasından 30 dakika sonra intratimpanik Ringer laktat (RL) solusyonu (0.1-0.3 mL) uygulandı Dekzametazon, RL solusyonu ve % 0,9 salin uygulamasına üç gün boyunca devam edildi. Çalışmanın sonunda, ABR testi uygulandı ve eşik değişimleri ölçüldü. Bulgular: 2. Grup taki sıçanlar uygulama öncesi ve sonrası işitme eşikleri arası ortalama fark 39,6 dB olup 4 kHz de 7,2 dB, 8 kHz de 8,4 dB,12 kHz de 71,1 dB ve 16 kHz de 71,8 dB lik eşik farkları saptandı. 3. grupta belirgin işitme kaybı gözlenmedi. Klik ve “tone-pips” uyaranlara karşı işitme eşikleri arası ortalama fark 4, 8, 12 ve 16 kHz frekansları için sırasıyla 1,60 dB, 4,75 dB, 8,70 dB, ve 4,26 dB olarak ölçüldü. Benzer bulgular 4. gruptada saptandı. Bu grupta klik ve “tone-pips” uyaranlara karşı işitme eşikleri arası ortalama fark 4, 8, 12 ve 16 kHz frekansları için sırasıyla 3,56 dB, 6,87 dB, 11,34 dB, ve 15,29 dB olarak ölçüldü. 2. gruba kıyasla 3. ve 4. grup sıçanlarda belirgin olarak işitmenin korunduğu saptandı. Ayrıca işitme fonksiyonları üzerine intratimpanik RL ve dekzametazonun herhangi bir yan etkisinin olmadığı ve bu iki ajanın sisplatin ototoksisitesinde kolay uygulanabilir, güvenli ve koruyucu olduklarını söyleyebiliriz. Sonuç: İntratimpanik RL solusyonu ve dekzametazon kolay uygulanabilen ve güvenli ajanlardır. kemoterapi protokollerinin ototoksik yan etkilerini azaltmak için klinik uygulamalara bu ajanların dahil edilmesi uygun olacaktır.

Sisplatin ototoksisitesinde dekzametazon ve laktat’ın koruyucu etkinliği

Aim: To compare the protective eff ect of dexamethasone and lactate against cisplatin-induced ototoxicity. Materials and methods: Th irty Wistar rats were randomly divided into 4 groups. Aft er the rats were sedated with intraperitoneal (IP) ketamine hydrochloride (50 mg/kg) and xylazine (7.5 mg/kg), baseline ABRs (auditory brainstem evoked responses) were measured in response to clicks and tone pips of 4, 8, 12, and 16 kHz. Aft er auditory thresholds were determined, the animals received drug administration as follows: Group 1 (n: 6) received intratympanic (IT) saline (0.9% NaCl) solution, Group 2 (n: 8) IP cisplatin (20 mg/kg) alone, Group 3 (n: 8) IT dexamethasone (0.1-0.3 mL), and Group 4 (n: 8) IT lactated Ringer’s (LR) solution (0.1-0.3 mL) followed aft er 30 min by 20 mg/kg cisplatin. Dexamethasone, LR solution, and saline application were continued for 3 days. At the end of the study, ABR testing was performed and threshold changes were recorded. Results: Group 2 animals showed marked hearing loss with average threshold shift s of 39,6 dB for clicks, 7.2 dB at 4 kHz, 8.4 dB at 8 kHz, 71.1 dB at 12 kHz and 71.8 dB at 16 kHz. No signifi cant loss was observed in Group 3 with average threshold shift s of 1.6 dB, 4.7 dB, 8.7 dB, and 4.2 dB for clicks and tone pips at 4, 8, 12, and 16 kHz, respectively. Similar fi ndings were observed in Group 4 with shift s of 3.5 dB, 6.8 dB, 11.3 dB, and 15.2 dB for clicks and tone pips at 4, 8, 12, and 16 kHz, respectively. Signifi cant protection was seen in Group 3 and 4 animals compared with Group 2 animals. Th ere was no side eff ect in IT administration of LR solution and dexamethasone for hearing functions. Both of these appear to be easier and safer to apply and have a usable protective eff ect against cisplatin ototoxicity. Conclusion: IT administration of LR solution and dexamethasone appear to be easy and safe to apply and have a useful protective eff ect. Clinical applications including these agents could be considered for use in order to reduce the side eff ects of ototoxic chemotherapy protocols.

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