title: Comparison of the effects of lipoic acid and glutathione against cisplatin-induced ototoxicity in auditory cells.
abstract: OBJECTIVE
  The aims of this study were to examine lipoic acid (LA)- or glutathione (GSH)-mediated protection against cytotoxicity following cisplatin exposure in HEI-OC1 auditory cells and measure the potential of LA and GSH to scavenge reactive oxygen species (ROS). This study also compares their protective effects and discusses the determination of a preventive or therapeutic dose.
  
  
  METHODS
  HEI-OC1 cells were pretreated with LA or GSH for 24 h and then exposed to 15 μM cisplatin for 48 h. The resulting cytotoxicity was measured using a cell counting kit-8, and intracellular ROS level was measured using flow cytometry. The protective or anti-ROS effects of LA and GSH were compared. Measurement of caspase 3, 8, 9 activity and Western blot analysis of PARP were performed.
  
  
  RESULTS
  Pretreatment with LA at 300 μM and GSH at 3 mM protected HEI-OC1 cells against cisplatin-induced cytotoxicity and significantly reduced the cisplatin-induced increase in ROS. LA showed a significantly more effective protection against cisplatin-induced ototoxicity compared to that shown by GSH (85.4% vs. 73.1% cell viability). Both LA and GSH showed the maximal protective effect at different concentrations in normal or cisplatin-induced cytotoxic conditions. The preventive or therapeutic dose for harmful conditions is quite different for the two drugs and needs careful adjustments.
  
  
  CONCLUSIONS
  This comparative study on the protective effects of LA and GSH against cisplatin-induced ototoxicity in an auditory cell line posed many challenges. Although LA and GSH showed a significant protective effect against cisplatin, the LA's effect was superior. The concentration at which the maximal protective effect of LA or GSH was noted was 3 times higher in cytotoxic conditions than in normal conditions, which suggests the need for drug dose adjustments based on the purpose (preventive or therapeutic).
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Korea University College of Medicine, South Korea. Electronic address: jams9098@daum.net.
authors.forename: Doo Yeob
authors.initials: DY
authors.lastname: Koo
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Korea University College of Medicine, South Korea. Electronic address: lshe5@naver.com.
authors.forename: Se Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Korea University College of Medicine, South Korea. Electronic address: ratm1017@naver.com.
authors.forename: SungHo
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Hallym University, College of Medicine, Inchon-ro 73, Seongbuk-Gu KR02841, Seoul, South Korea. Electronic address: brune77@naver.com.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Korea University College of Medicine, South Korea. Electronic address: ranccoon@naver.com.
authors.forename: Hak Hyun
authors.initials: HH
authors.lastname: Jung
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Korea University College of Medicine, South Korea. Electronic address: logopas@korea.ac.kr.
authors.forename: Gi Jung
authors.initials: GJ
authors.lastname: Im
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D019610:Cytoprotection; D005434:Flow Cytometry; D005978:Glutathione / Q000494:pharmacology*; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D008063:Thioctic Acid; D020169:Caspases; D005978:Glutathione; D002945:Cisplatin
keywords: Cisplatin; Glutathione; Lipoic acid; Ototoxicity; Reactive oxygen species