Eur Arch Otorhinolaryngol (2012) 269:45–52 DOI 10.1007/s00405-011-1582-2 123 OTOLOGY Reduction of cisplatin ototoxicity in rats by oral administration of pomegranate extract Zahide Mine Yazici · Aysenur Meric · Ahmet Midi · Yasar Volkan ArÂnc · Volkan Kahya · Gunter HafÂz Received: 4 January 2011 / Accepted: 14 March 2011 / Published online: 27 March 2011  Springer-Verlag 2011 Abstract The aim of this study was to investigate the eVec- tiveness of the oral administration of pomegranate extract (PE) as a protective agent against cisplatin-induced ototoxicity. The study included a prospective, controlled animal study Group 1 (n = 6), received no cisplatin or PE, and group 2 (n = 6) received cisplatin at 8 mg/kg/day for 3 consecutive days. Group 3 (n = 6) received not only cisplatin at 8 mg/kg/day for 3 consecutive days, but also received PE (100 L/day) via gav- age for 5 days prior to the cisplatin injection and for 3 days concomitantly with the cisplatin injections. To measure cis- platin ototoxic eVects, “distortion product otoacoustic emis- sions” (DPOAE) were analyzed 3 days before and after the cisplatin injections. Histological changes in the cochleas were observed by light microscopy. Compared with group 3, the DPOAE amplitudes of group 2 decreased signiWcantly. Among the groups, there was a statistically signiWcant diVer- ence in basal and mid turn external ciliated cells (ECC) num- ber, but there was no statistically signiWcant diVerence in apical turn. DiVerences in stria vascularis (SV) changes were statisti- cally signiWcant between the groups, and the median score for SV injury was signiWcantly greater in group 2 than in group 3. DiVerences in the median scores for SGC changes being sig- niWcantly greater in group 2 than in group 3. In conclusion, these results indicated that oral administration of PE aVorded statistically signiWcant protection to the cochlea in rats from cisplatin toxicity, and thus, oral experimental dose of PE administration may have a protective eVect against cisplatin ototoxicity in rats. Keywords Cisplatin · Ototoxicity · Pomegranate · Histopathology Introduction Cisplatin (cis-diamminedichloroplatinum II) is commonly used to treat a variety of neoplasms, especially those of the head and neck. The anticancer eVect of cisplatin is due to several mechanisms, including the formation of DNA adducts and the production of reactive oxygen species (ROS) [1]. Side eVects include ototoxicity, nephrotoxicity, marrow suppression, and gastrointestinal disorders [2], with ototoxicity observed in up to 36% of patients receiving cisplatin [3]. Ototoxicity may occur within hours to days after treatment with cisplatin [4]. Hearing loss appears to be dose-related, cumulative, bilateral, usually permanent, and occurs initially at higher frequencies. Z. M. Yazici Clinic of Otorhinolaryngology, Head and Neck Surgery, BakÂrköy Research and Training Hospital, Istanbul, Turkey A. Meric · V. Kahya Department of Otorhinolaryngology, Head and Neck Surgery, Bezm-i Alem VakÂf Gureba University, Istanbul, Turkey A. Midi Department of Pathology, Maltepe University School of Medicine, Istanbul, Turkey Y. V. ArÂnc Department of Chemistry Engineering, Istanbul Technical University, Istanbul, Turkey G. HafÂz Department of Otorhinolaryngology, Head and Neck Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey Z. M. Yazici (&) Bakirköy Efitim ve AraotÂrma Hastanesi, Kulak Burun Bogaz ABD, TevWk Saflam cad., No: 13 Zuhuratbaba, 34147 Istanbul, Turkey e-mail: minealmaz@yahoo.com