title: Attenuation of streptomycin ototoxicity by tetramethylpyrazine in guinea pig cochlea.
abstract: OBJECTIVE
  Tetramethylpyrazine has been suggested to have a therapeutic effect on impaired hearing that is induced by aminoglycoside antibiotics. However, its effectiveness on streptomycin ototoxicity and its cellular mechanisms are relatively unknown. Here we investigate the protective effect of tetramethylpyrazine on streptomycin-induced ototoxicity in guinea pig cochlea.
  
  
  METHODS
  Prospective randomized laboratory study.
  
  
  METHODS
  Hearing Research Laboratory of China Medical University.
  
  
  METHODS
  Adult guinea pigs were randomized to 4 groups. Hearing sensitivity of guinea pigs was tested by auditory brainstem response measurements before streptomycin exposure and again 10 days later. The cochlear tissues were prepared for electron microscopy and immunohistochemical staining of heat shock protein 70 (HSP70). The effect of tetramethylpyrazine on streptomycin-induced activation of caspase-3 was evaluated by Western blotting.
  
  
  RESULTS
  Co-therapy with tetramethylpyrazine reduced a profound streptomycin-induced auditory threshold shift compared with streptomycin treatment alone (P = .0002 or P = .00008). Tetramethylpyrazine also attenuated the structural disruption in streptomycin-treated outer hair cells and marginal cells of vascular stria by transmission electronic microscopy and scanning electronic microscopy, respectively. Moreover, tetramethylpyrazine decreased the streptomycin-stimulated expressions of HSP70 and caspase-3. The correlation analysis demonstrated that HSP70 expression had a positive correlation with auditory brainstem response thresholds (|R| = 0.6-0.9, P = .0073 or P = .0169).
  
  
  CONCLUSIONS
  Our data suggest that the protective effect of tetramethylpyrazine on hearing function is associated with the reduction of stress response and inhibition of apoptosis. Tetramethylpyrazine may have therapeutic potential for patients with ototoxicity diseases.
authors.affiliation: Hearing Research Laboratory, China Medical University, Shenyang, Liaoning, China Department of Physiology, China Medical University, Shenyang, Liaoning, China chengcui_999@yahoo.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cui
authors.affiliation: Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Dajun
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Physiology, China Medical University, Shenyang, Liaoning, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Qin
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001309:Auditory Threshold; D003051:Cochlea / Q000187:drug effects; D006168:Guinea Pigs; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism; D006309:Hearing / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D011446:Prospective Studies; D011719:Pyrazines / Q000627:therapeutic use*; D013307:Streptomycin / Q000009:adverse effects*
chemical_list: D000900:Anti-Bacterial Agents; D018840:HSP70 Heat-Shock Proteins; D011719:Pyrazines; C017953:tetramethylpyrazine; D013307:Streptomycin
keywords: caspase-3; electronic microscope; heat shock protein 70; ototoxicity; tetramethylpyrazine