title: Rapamycin alleviates cisplatin-induced ototoxicity in vivo.
abstract: BACKGROUND
  Cisplatin-induced ototoxicity affects a high percentage of new cancer patients worldwide. The detailed mechanism of cisplatin-induced ototoxicity is not completely understood. We investigated whether rapamycin could protect rats from cisplatin-induced ototoxicity.
  
  
  METHODS
  Forty-eight male Wistar rats were randomly divided into six groups. Three groups were intraperitoneally (IP) infused with cisplatin at a dose of 16 mg/kg and immediately injected with either dimethylsulfoxide (DMSO), rapamycin, or chloroquine (CQ). The remaining three groups were treated with rapamycin, CQ, or saline alone. The auditory brainstem response (ABR) test was performed to detect the rats' hearing status. Serum was isolated to measure the level of the oxidative marker malondialdehyde (MDA), the basilar membrane was prepared to count the outer hair cell loss, and soft tissue samples extracted from the cochleae were lysed to analyze the microtubule-associated protein light chain 3 (LC3) and Beclin-1.
  
  
  RESULTS
  The rapamycin treatment significantly attenuated cisplatin-induced hearing loss, decreased oxidative stress, and alleviated the hair cell damage that was associated with the upregulation of the LC3-II/GAPDH ratio and increased Beclin-1 expression.
  
  
  CONCLUSIONS
  Our results demonstrated that rapamycin has an otoprotective effect; it attenuates cisplatin-induced ototoxicity, probably by attenuating oxidative damage and inducing autophagy.
authors.affiliation: Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Fang
authors.affiliation: Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: xhjent@163.com.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Xiao
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D002945:Cisplatin; D008315:Malondialdehyde; D008869:Microtubule-Associated Proteins; D020123:Sirolimus; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat
keywords: Autophagy; Cisplatin ototoxicity; Inner Ear; Oxidative stress; Rapamycin