Otomikoz Tedavisinde Kullanılan Ciclopiroxolamine'in Ototoksisitesini Distortion Product Otoacoustic Emissions (Dpoae) Yardımıyla Değerlendirilmesi

Abstract

Ama~: Bu yah~ma; klinikle ili~kili mantar ve mayalann tumline yakmml inhibe eden, azolgrubu ilaylara rezistan mantarlara, gram negatif ve pozitif bakterilere de kar~l etkili olan veantiinflamatuar ozelligi olan ciclopiroxolamine ' in orta kulaga tatbik edildiginde ototoksiketkisinin ara~tmlmasl amaclyla yapIlml~tIr.Dizayn: Deneysel hayvan yah~maSlMateryal & Metot: Kulak muayene bulgularl ve Distortion Product Otoacoustic Emissions(DPOAE) olyumleri normal toplam 18 di~i Wistar cinsi albino rat, randomize olarak 6'~arh 3gruba aynldl ve gruplann DPOAE ortalamalan hesaplandl. Butlin frekanslarda her uy gruparasmda istatiksel ayldan fark olmadlgl tespit edildi. Butun ratlann sag kulak zarl arka kadramperfore edildi, tekrar DPOAE olyumleri ahndl ve ortalamalarda anlamh fark olmadlgl tespitedi ldi. Yapllan perforasyondan bir klsml dl~ kulak yolunda bir klsml orta kulakta yuvarlakpeIlcere lokalizasyonuna yakm bir ~ekilde gel foam yerlqtirildi. Grup l ' e %0,9' luk serumfiz}'olojik (negatif kontrol), grup 2' ye 40mg/ml gentamisin (pozitif kontrol) ve grup 3' e 10mg/ml ciclopiroxolamine (yah~ma grubu) 2 hafta sureyle gunde 2xO,1 ml gel foam yoluylaorta kulaga tatbik edildi. Son ilay tatbikinden bir ay sonra ratlar tekrar muayene edildi vekontrol DPOAE olyumleri yapIldl.Bulgular: Serum fizyolojik (SF) tatbik edilen grup l ' in ortalamasl deney oncesi DPOAEortalamalanna gore deney sonraSl 3 ve 8 kHz' de; gentamisin tatbik edilen grup 2' ninortalamasl 3, 4, 6 ve 8 kHz' de; ciclopiroxolamine tatbik edilen grup 3'un ortalamasl 3, 6 ve 8kHz' de anlamh olarak du~uk bulunmu~tur. Ciclopiroxolamine DPOAE degerlerini 3, 6 ve 8kHz frekanslarmda hem SF' ten hem de gentamisinden daha belirgin olarak dii~urmu~tur.Ancak veriler incelendiginde ciclopiroxolamine' nin neden oldugu du~ii~; 3 kHz' de SF' egore, 6 ve 8 khz' de ise hem SF hem de gentamisine gore istatistiksel olarak anlamhbulunmu~tur. Ciclopiroxolamine verilen grup 3' teki biitlin ratlar genel durum bozuklugu,takipne, sol unum zorlugu ve motor hareketlerde yava~lama geli~tirdi ve 18 numarah rat 7. gunexitus oldu.Sonu~: Ciclopiroxolamine orta kulaga tatbik edildiginde koklear fonksiyonlar etkilenmi~ vesistemik veya norotoksik etkiler izlenmi~tir.Dizin terimleri: Ciclopiroxolamine, ototoksisite, DPOAE, orta kulak, rat

Objective: Ciclopiroxolamine inhibits nearly all of the clinically relevant dermatophytes,yeasts and moulds. It has an effect on some azole-resistant moulds species, gram negative/positive bacterias and has an anti-inflammatory feature. The aim of this study is to evaluatethe ototoxic effect of ciclopiroxolamine administration in to the middle ear.Design: Experimental animal studyMaterial & Method: Eighteen female Wistar albino rats, have normal ear examinationfindings and Distortion Product Otoacoustic Emissions (DPOAE) measurements, randomlydivided into 3 groups. DPOAE results were calculated for each grups, no statisticallysignificant difference were found. The posterior dial of the right tympanic membrane wasperforated in all rats. After the perforation, DPOAE values was measured again and there wasno significant difference between the groups. Gel foam was placed through the perforationand located from outer ear to close to round window. The solutions were applied via the gelfoam to middle ear, [group 1 saline 0.9% (negative control), group 2 gentamicin 40mg/ml(positive control), group 3 ciclopiroxolan1ine 10mg/ml (study group)] two times a day (2xO,1ml) for 2 weeks. Rats ears reexan1inated after one mounth from last application and DPOAEmeasuraments were repeated.Results: DPOAE results were compared between before and after application. Afterapplication DPOAE averages were found significantly lower in the 3 and 8 kHz in group 1; 3,4, 6 and 8 kHz in group 2 and 3, 6 and 8 kHz in group 3 than before examination.Ciclopiroxolamine was decreased DPOAE's numeric values more than salin and gentamicinein 3, 6, and 8 kHz frequencies. However, data analysis decline that the decrease DPOAEval lles caused by ciclopiroxolamine were statistically significant in 3 kHz according to salineand statistically significant in 6 and 8 kHz according to the both SF and gentamicine. All ratsin group 3 developed tachypnea, respiratory distress and deceleration of motor movements.One rat died in seventh day.COl1clusions: When ciclopiroxolamine was applied to the middle ear, cochlear functionsinfluenced and systemic or neurotoxic side effects observed.Key words: Ciciopiroxoiamine, ototoxicity, DPOAE, middle ear, rat