title: Histone deacetylase inhibitor sodium butyrate attenuates gentamicin-induced hearing loss in vivo.
abstract: OBJECTIVE
  Although histone deacetylase (HDAC) inhibition has been shown to protect against gentamicin (GM)-induced hearing loss in vitro, its protective effect has not been proven in vivo. In the present study, the aim was to investigate the protective effect of sodium butyrate (NaB), a specific HDAC inhibitor, on GM-induced ototoxicity in vivo.
  
  
  METHODS
  Forty 8-week-old albino guinea pigs were divided into two experimental groups. Group 1 (n=10) underwent bilateral ear surgery to place sponges (0.3mm(3)) permeated with NaB (10μl, 100mg/ml) and physiological saline (10μl; control) in the right and left round window niches, respectively. The sponges were left in place for 15days to evaluate the effects of NaB at the applied concentration. Group 2 (n=30) underwent the same bilateral ear surgery described for Group 1, except three days after surgery, the animals received intramuscular GM injections (200mg/kg/day) for 5 consecutive days. Seven days after the final GM injection, the protective effects of NaB were examined.
  
  
  RESULTS
  After 15days of NaB treatment (10μl, 100mg/ml), an increase in histone acetylation was detected in Corti organ samples. Auditory brainstem response (ABR) threshold shifts and hair cell loss were also reduced in NaB-treated ears after GM administration. Furthermore, GM treatment increased HDAC1 expression in outer hair cells (OHCs) in vivo, and NaB blocked this action.
  
  
  CONCLUSIONS
  GM increases HDAC1 expression in OHCs, and NaB is able to block this action. Thus, it appears that the HDAC inhibitor, NaB, attenuates GM-induced hearing loss in guinea pigs.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, 17 Changle Western Road, Xi'an, China; Department of Otolaryngology-Head and Neck Surgery, Xi'an Children's Hospital, Shanxi, Xi'an, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, 17 Changle Western Road, Xi'an, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, 17 Changle Western Road, Xi'an, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, 17 Changle Western Road, Xi'an, China.
authors.forename: Peng-zhi
authors.initials: PZ
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, 17 Changle Western Road, Xi'an, China.
authors.forename: Ze-tao
authors.initials: ZT
authors.lastname: Shi
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, 17 Changle Western Road, Xi'an, China.
authors.forename: Li-ting
authors.initials: LT
authors.lastname: Wen
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, 17 Changle Western Road, Xi'an, China.
authors.forename: Jian-hua
authors.initials: JH
authors.lastname: Qiu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, 17 Changle Western Road, Xi'an, China. Electronic address: chenfq2@yahoo.com.
authors.forename: Fu-quan
authors.initials: FQ
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005839:Gentamicins / Q000494:pharmacology / Q000633:toxicity*; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects; D034381:Hearing Loss / Q000139:chemically induced* / Q000188:drug therapy*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D008297:Male; D011897:Random Allocation; D012016:Reference Values
chemical_list: D005839:Gentamicins; D056572:Histone Deacetylase Inhibitors