title: Friend or foe? Effect of oral resveratrol on cisplatin ototoxicity.
abstract: OBJECTIVE
  Our objectives were to study effects of orally administered resveratrol (RV) against cisplatin (CDDP) ototoxicity in different doses and to investigate ultrastructural changes in the cochlea and brainstem.
  
  
  METHODS
  In vivo study using an animal model.
  
  
  METHODS
  Thirty-two male Wistar albino rats were divided into six groups. Baseline distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) measurements were made. In groups I, II, and III, only saline, RV, and CDDP were given, respectively. Group IV, V, and VI animals were administered 10 mg/kg/day, 1 mg/kg/day, and 0.1 mg/kg/day of RV for 10 days, respectively, before 16 mg/kg CDDP injections were administered on day 11. All animals were sacrificed after repeated DPOAEs and ABR measurements were made on day 14. Cochleas of animals were investigated with transmission electron microscopy. Apoptosis were investigated with caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in the brainstem.
  
  
  RESULTS
  In groups IV and V, DPOAEs and ABR findings revealed that oral administration of RV 10 mg/kg/day and 1 mg/kg/day doses before CDDP injection enhanced ototoxicity. In group VI, electomicroscopy revealed better ultrastructural findings than in the cisplatin group; however, these changes were not reflected in the audiological findings accordingly.
  
  
  CONCLUSIONS
  Our results implied that there were noticeable differences between different oral RV doses used for cisplatin ototoxicity. Especially in higher doses, RV was observed to enhance cisplatin ototoxicity.
authors.affiliation: Department of Otorhinolaryngology, Dokuz Eylül University School Of Medicine, Izmir, Turkey.
authors.forename: Yüksel
authors.initials: Y
authors.lastname: Olgun
authors.forename: Günay
authors.initials: G
authors.lastname: Kırkım
authors.forename: Efsun
authors.initials: E
authors.lastname: Kolatan
authors.forename: Müge
authors.initials: M
authors.lastname: Kıray
authors.forename: Alper
authors.initials: A
authors.lastname: Bagrıyanık
authors.forename: Aybüke
authors.initials: A
authors.lastname: Olgun
authors.forename: Deniz Cakır
authors.initials: DC
authors.lastname: Kızmazoglu
authors.forename: Hülya
authors.initials: H
authors.lastname: Ellıdokuz
authors.forename: Bulent
authors.initials: B
authors.lastname: Serbetcıoglu
authors.forename: Zekiye
authors.initials: Z
authors.lastname: Altun
authors.forename: Safiye
authors.initials: S
authors.lastname: Aktas
authors.forename: Osman
authors.initials: O
authors.lastname: Yılmaz
authors.forename: Enis Alpin
authors.initials: EA
authors.lastname: Günerı
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity; D000975:Antioxidants / Q000008:administration & dosage*; D001707:Biopsy, Needle; D053148:Caspase 3 / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000648:ultrastructure; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000517:prevention & control*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D046529:Microscopy, Electron, Transmission; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D013267:Stilbenes; D053148:Caspase 3; D002945:Cisplatin; D000077185:Resveratrol
keywords: Cisplatin; ototoxicity; resveratrol