title: Drug-mediated ototoxicity and tinnitus: alleviation with melatonin.
abstract: This review evaluates the published basic science and clinical reports related to the role of melatonin in reducing the side effects of aminoglycosides and the cancer chemotherapeutic agent cisplatin, in the cochlea and vestibule of the inner ear. A thorough search of the literature was performed using available databases for the purpose of uncovering articles applicable to the current review. Cochlear function was most frequently evaluated by measuring otoacoustic emissions and their distortion products after animals were treated with cytotoxic drugs alone or in combination with melatonin. Vestibular damage due to aminoglycosides was evaluated by estimating hair cell loss in explanted utricles of newborn rats. Tinnitus was assessed in patients who received melatonin using a visual analogue scale or the Tinnitus Handicap Inventory. Compared to a mixture of antioxidants which included tocopherol, ascorbate, glutathione and N-acetyl-cysteine, melatonin, also a documented antioxidant, was estimated to be up to 150 times more effective in limiting the cochlear side effects, evaluated using otoacoustic emission distortion products, of gentamicin, tobramycin and cisplatin. In a dose-response manner, melatonin also reduced vestibular hair cell loss due to gentamicin treatment in explanted utricles of newborn rats. Finally, melatonin (3 mg daily) limited subjective tinnitus in patients. These findings suggest the potential use of melatonin to combat the ototoxicity of aminoglycosides and cancer chemotherapeutic agents. Additional studies at both the experimental and clinical levels should be performed to further document the actions of melatonin at the cochlear and vestibular levels to further clarify the protective mechanisms of action of this ubiquitously-acting molecule. Melatonin's low cost and minimal toxicity profile supports its use to protect the inner ear from drug-mediated damage.
authors.affiliation: Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio, TX 78229, USA. reiter@uthscsa.edu
authors.forename: R J
authors.initials: RJ
authors.lastname: Reiter
authors.forename: D-X
authors.initials: DX
authors.lastname: Tan
authors.forename: A
authors.initials: A
authors.lastname: Korkmaz
authors.forename: L
authors.initials: L
authors.lastname: Fuentes-Broto
mesh_terms: D000617:Aminoglycosides / Q000009:adverse effects; D000818:Animals; D002945:Cisplatin / Q000009:adverse effects; D018849:Controlled Clinical Trials as Topic / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007759:Labyrinth Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D008550:Melatonin / Q000627:therapeutic use*; D014012:Tinnitus / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000617:Aminoglycosides; D008550:Melatonin; D002945:Cisplatin