Akademik Veri Yönetim Sistemi
Dokuz Eylül Üniversitesi Tıp Fakültesi Dergisi, cilt.36, sa.3, ss.309-320, 2022 (Hakemli Dergi)
Aim: It was aimed to evaluate in-vivo whether darbepoetin-alpha (DPO)
application has a preventive role in the cisplatin-induced ototoxic effect.
Materials and Methods: In the study, four groups were formed using 28 Wistar
albino rats. Group 1 (intraperitoneal) IP saline given control group, Group 2
cisplatin (16mg/kg IP single dose), Group 3 DPO (25 μg/kg IP), and Group 4
is the group in which a single dose of 25 μg/kg IP DPO was administered 24
hours before and half an hour after cisplatin administration. Distortion product
otoacoustic emission (DPOAE) and brainstem auditory evoked potentials
(BAEP) were performed on rats before agent administration and on the 7th day
of the experiment. After hearing measurements, the rats were sacrificed.
Apoptotic cell death in ear tissue, caspase-3, -8, -9 expression, Inducible Nitric
Oxide Synthase (iNOS), Neuronal Nitric Oxide Synthase (nNOS) expression
levels, antioxidant Nrf2 (Nuclear factor (erythroid-derived 2)) - like 2) and
related Heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1
(NQQ1) were studied by immunohistochemical method. Serum glutathione
(GSH) and anti-inflammatory TNF-α and IL-1β protein levels were determined
using ELISA kits.
Results: The hearing loss was detected at all frequencies showing ototoxic
effects compared to control in hearing measurements with cisplatin
application. In the examinations performed at the immunohistochemical tissue
level, structural changes in the inner ear, necrosis, and necroptosis in the brain
and nerve tissues were detected in the cisplatin-administered group. The
preventive effects of darbepoetin on the inner ear and brain damage induced
by cisplatin are detected by apoptotic protein expressions and oxidative stressrelated markers, iNOS and nNOS,