Kemoradyoterapıye bağlı ototoksısıte ve darbepoetının etkısı


Tezin Türü: Doktora

Tezin Yürütüldüğü Kurum: Dokuz Eylül Üniversitesi, Sağlık Bilimleri Enstitüsü, Türkiye

Tezin Onay Tarihi: 2021

Tezin Dili: Türkçe

Öğrenci: ASUMAN FEDA BAYRAK

Danışman: Zekiye Sultan Altun

Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu

Özet:

This study aims to determine and evaluate whether the administration of Darbepoetin (DPO) has a preventive effect against ototoxic effects due to cisplatin on Wistar rats. DPO’s potential protective effect against ototoxicity will be examined through nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and target genes.

In the study; 28 wistar albino rats were used to form, control, cisplatin (16mg/kg IP ), DPO (25 ug/kg, IP), DPO administered before cisplatin groups, Apoptotic cell death was determined by TUNEL analysis by in situ hybridization in ear tissue; caspase 3, 8, 9 levels immunohistochemical methods, Nrf-2 and Nrf-2 associated with NrQ2 antioxidant and iNOS, nNOS, protein expressions will be studied by tissue immunohistochemical methods. Each group will be evaluated in comparison. 

With cisplatin application, hearing loss was detected in all frequencies showing ototoxic effects compared to the control group. In the examinations performed at the level of immunohistochemical tissue, structural changes in the inner ear, necrosis and necroptosis in the brain and nerve tissues were detected in the ciplatin group. Effects of darbopeotin on nitric oxide system while cisplatin prevented the inner ear and brain damage, both apoptotic protein expressions and nrf-2, associated with oxidative stress, on NQO1 was also detected.

In this study, ototoxicity, which consists of cisplatin has been shown at functional level. Darbopoetin has been shown to protect against inner ear and brain damage due to cisplatin reducing apoptosis, increasing anti-oxidant protein levels, preventing oxidative stress.