title: Effect of Transtympanic Injection of Melatonin on Cisplatin-Induced Ototoxicity.
abstract: OBJECTIVE
  Cisplatin is a chemotherapeutic agent that is widely used in cancer treatment. Numerous side effects have been detected, one of which is ototoxicity. Melatonin, a product of the pineal gland, has a neuroendocrinoimmunological role in vertebrates. In the present study, we investigated the effects of melatonin on cisplatin-induced ototoxicity.
  
  
  METHODS
  Twenty-four Wistar albino rats were divided into three groups. Group 1 was administered both intraperitoneal and transtympanic saline; Group 2, 12 mg/kg of intraperitoneal single-dose cisplatin and transtympanic saline; and Group 3, 12 mg/kg of intraperitoneal single-dose cisplatin and 0.1 mg/mL of transtympanic melatonin for 5 days. Before and after the procedure, distortion product otoacoustic emissions and auditory brainstem responses of all the rats were measured. At the end of the procedure, the cochleas of the rats were investigated at the microscopic level.
  
  
  RESULTS
  Group 3 had lesser threshold shift in otoacoustic emissions and auditory brainstem responses at all frequencies than Group 2 (p<0.005). The difference was not significant between Group 1 and Group 3. On the microscopic level, more epithelial loss and less TNF staining were detected in Group 2 than in Group 3.
  
  
  CONCLUSIONS
  As an antioxidant and immune modulator, melatonin is effective against cisplatin ototoxicity. Both hearing thresholds and tissue investigations supported this conclusion. Melatonin can also be used to treat cisplatin ototoxicity using transtympanic local application in lower doses.
authors.affiliation: Department of Otorhinolaryngology, Prof. Dr. Celal Ertuğ Etimesgut State Hospital, Ankara, Turkey. mgokhandemir@yahoo.com.
authors.forename: Mehmet Gökhan
authors.initials: MG
authors.lastname: Demir
authors.forename: Niyazi
authors.initials: N
authors.lastname: Altıntoprak
authors.forename: Sedat
authors.initials: S
authors.lastname: Aydın
authors.forename: Ebru
authors.initials: E
authors.lastname: Kösemihal
authors.forename: Kayhan
authors.initials: K
authors.lastname: Başak
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000008:administration & dosage*; D001309:Auditory Threshold / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D003051:Cochlea / Q000473:pathology; D004427:Ear Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004848:Epithelium / Q000473:pathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D007267:Injections; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects; D017208:Rats, Wistar; D014432:Tympanic Membrane
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D008550:Melatonin; D002945:Cisplatin