title: Assessment of D-methionine protecting cisplatin-induced otolith toxicity by vestibular-evoked myogenic potential tests, ATPase activities and oxidative state in guinea pigs.
abstract: To date, inadequate study has been devoted to the toxic vestibular effects caused by cisplatin. In addition, no electrophysiological examination has been conducted to assess cisplatin-induced otolith toxicity. The purposes of this study are thus two-fold: 1) to determine whether cervical vestibular-evoked myogenic potentials (VEMPs) and ocular VEMPs are practical electrophysiological methods of testing for cisplatin-induced otolith toxicity and 2) to examine if D-methionine (D-met) pre-injection would protect the otolith organs against cisplatin-induced changes in enzyme activities and/or oxidative status. Guinea pigs were intraperitoneally treated once daily with the following injections for seven consecutive days: sterile 0.9% saline control, cisplatin (5 mg/kg) only, D-met (300 mg/kg) only, or a combination of d-met (300 mg/kg) and cisplatin (5 mg/kg), respectively, with a 30 minute window in between. Each animal underwent the oVEMP and cVEMP tests before and after treatment. The changes in the biochemistry of the otolith organs, including membranous Na(+), K(+)-ATPase and Ca(2+)-ATPase, lipid peroxidation (LPO) levels and nitric oxide (NO) levels, were also evaluated. In the cisplatin-only treated guinea pigs, the mean amplitudes of the oVEMP tests were significantly (p<0.05) decreased when compared to the other three groups. In guinea pigs receiving both D-met and cisplatin, the amplitudes of their oVEMP tests were significantly larger (p<0.05) than those of the cisplatin-only group, but smaller (p<0.05) than those of the saline control or D-met-only group. However, no significant difference of the amplitudes of cVEMP tests was noted among the four groups. In comparison with the other three groups, the cisplatin-only group had the lowest (ps<0.05) mean Na(+), K(+)-ATPase and Ca(2+)-ATPase, and the highest (ps<0.05) LPO and NO levels. The oVEMP tests were feasible for the evaluation of cisplatin-related otolith dysfunction. D-Met attenuated the reduced ATPase activities and increased oxidative stress induced by cisplatin toxicity in the otolith organs.
authors.affiliation: Department and Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan; Oriental Institute of Technology, Taipei, Taiwan.
authors.forename: Wu-Chia
authors.initials: WC
authors.lastname: Lo
authors.affiliation: Department of Otolaryngology, Far Eastern Memorial Hospital, Taipei, Taiwan.
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Chang
authors.affiliation: Department of Otolaryngology, Far Eastern Memorial Hospital, Taipei, Taiwan.
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Liao
authors.affiliation: Department of Otolaryngology, Far Eastern Memorial Hospital, Taipei, Taiwan.
authors.forename: Chi-Te
authors.initials: CT
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yi-Ho
authors.initials: YH
authors.lastname: Young
authors.affiliation: Department and Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: ipohdamu@gmail.com.
authors.forename: Yih-Leong
authors.initials: YL
authors.lastname: Chang
authors.affiliation: Department of Otolaryngology, Far Eastern Memorial Hospital, Taipei, Taiwan; Oriental Institute of Technology, Taipei, Taiwan. Electronic address: pwchengpw@gmail.com.
authors.forename: Po-Wen
authors.initials: PW
authors.lastname: Cheng
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D006168:Guinea Pigs; D006851:Hydrochloric Acid / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008715:Methionine / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D010037:Otolithic Membrane / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D015837:Vestibular Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D058585:Vestibular Evoked Myogenic Potentials / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D009569:Nitric Oxide; D008315:Malondialdehyde; D008715:Methionine; D000251:Adenosine Triphosphatases; D002945:Cisplatin; D006851:Hydrochloric Acid
keywords: Bone-conducted vibration; Lipid peroxidation; Nitric oxide; Vestibular-evoked myogenic potential; d-Methionine