title: Dynamic distribution of ototoxic gentamicin entry into inner hair cells of mice.
abstract: CONCLUSIONS
  Dynamic distribution of ototoxic gentamicin entry into inner hair cells (IHCs) may cause an interruption of cochlear ribbon synapse.
  
  
  OBJECTIVE
  To explore the pattern of uptake of gentamicin into IHCs, as well as its possible contribution to hearing loss.
  
  
  METHODS
  Adult C57 mice were injected intraperitoneally with gentamicin (100 mg/kg, conjugated with Texas Red ester) continuously for 14 days. The hearing thresholds were detected by auditory brainstem response (ABR) examinations. Immunostaining and confocal microscopy were utilized to trace gentamicin distribution, as well as the expression of RIBEYE/CtBP2 in mouse IHCs. Scanning electron microscopy (SEM) observation was used to find possible alterations of stereocilia.
  
  
  RESULTS
  The distribution of gentamicin in IHCs was first found on the 4th day and the accumulation of gentamicin was increased significantly on the 7th day after treatment, corresponding to the maximal elevation of the hearing threshold. However, the accumulation of gentamicin on the 14th day did not show significant differences compared with the level found on the 7th day. In addition, the uptake of gentamicin was excessively identified at or near the synaptic ribbons of IHCs throughout the 4th, 7th, and 14th days after the treatment, suggesting that cochlear ribbon synapses could be affected by ototoxic gentamicin exposure.
authors: Department of Otolaryngology, Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital , Beijing.
authors: Ke
authors: K
authors: Liu
authors: Chuang
authors: C
authors: Shi
authors: Yuhan
authors: Y
authors: Sun
authors: Yice
authors: Y
authors: Xu
authors: Lei
authors: L
authors: Shi
authors: Lin
authors: L
authors: Shi
authors: Xiaoyu
authors: X
authors: Wang
authors: Fei
authors: F
authors: Ji
authors: Zhaohui
authors: Z
authors: Hou
authors: Shiming
authors: S
authors: Yang
mesh_terms: D000429:Alcohol Oxidoreductases; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000633:toxicity; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000187:drug effects; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005500:Follow-Up Studies; D005839:Gentamicins / Q000493:pharmacokinetics* / Q000633:toxicity; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D034381:Hearing Loss / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D005839:Gentamicins; D010750:Phosphoproteins; D000429:Alcohol Oxidoreductases; C111341:Ctbp2 protein, mouse