Akbarnejad, Zeinab

Cisplatin is an imperative drug in the treatment of a wide range of cancers. However, it has various side effects including ototoxicity causing bilateral sensorineural hearing loss. Despite lacking a clearly defined mechanism, Reactive Oxygen Species (ROS) production and damage to Outer Hair Cells (OHCs) have been implicated as possible culprits. The ideal otoprotective drug would target inflammation and oxidative stress without compromising cisplatin’s efficacy. This study aimed to scrutinize whether intratympanic Epigallocatechin-3-Gallate (EGCG) exhibits a protective effect against cisplatin-related ototoxicity. Twenty-four adult male Wistar rats (8–10 weeks, 200–250 g) were randomly divided into four groups (n=6 per group): Cisplatin, EGCG, Cisplatin+EGCG, and Control. Cisplatin (15 mg/kg) was administered intraperitoneally, and/or EGCG (10 mg/mL, 200 μL) was injected transtympanically into the right ear, depending on group assignment. Control rats received intratympanic distilled water. After 72 h, auditory function was assessed by Auditory Brain Response (ABR), followed by histopathological and Signal Transducer and Activator of Transcription-1 (STAT1) immunohistochemistry evaluation of cochlear sections. All animals underwent baseline otoscopy and ABR to rule out pre-existing hearing impairment. Data were analyzed using repeated measures of Analysis of Variance (ANOVA) and paired t-tests for ABR thresholds, and Kruskal–Wallis/Mann–Whitney tests for histopathological and Immunohistochemistry (IHC) scoring. Statistical significance was defined as p <0.05. EGCG injections failed to prevent hearing threshold increases in the Cisplatin group. According to histopathologic and STAT-1 IHC evaluation in the treatment group, reduced OHC damage, apoptosis, and cochlear hyperemia were observed. Administration of EGCG alleviated apoptosis and prevented OHCs damage in animals. However, it could not prevent hearing loss significantly.