title: Adenosine amine congener as a cochlear rescue agent.
abstract: We have previously shown that adenosine amine congener (ADAC), a selective A1 adenosine receptor agonist, can ameliorate noise- and cisplatin-induced cochlear injury. Here we demonstrate the dose-dependent rescue effects of ADAC on noise-induced cochlear injury in a rat model and establish the time window for treatment.
  
  
  METHODS
  ADAC (25-300 μg/kg) was administered intraperitoneally to Wistar rats (8-10 weeks old) at intervals (6-72 hours) after exposure to traumatic noise (8-16 kHz, 110 dB sound pressure level, 2 hours). Hearing sensitivity was assessed using auditory brainstem responses (ABR) before and 12 days after noise exposure. Pharmacokinetic studies investigated ADAC concentrations in plasma after systemic (intravenous) administration.
  
  
  RESULTS
  ADAC was most effective in the first 24 hours after noise exposure at doses >50 μg/kg, providing up to 21 dB protection (averaged across 8-28 kHz). Pharmacokinetic studies demonstrated a short (5 min) half-life of ADAC in plasma after intravenous administration without detection of degradation products.
  
  
  CONCLUSIONS
  Our data show that ADAC mitigates noise-induced hearing loss in a dose- and time-dependent manner, but further studies are required to establish its translation as a clinical otological treatment.
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand ; Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Srdjan M
authors.initials: SM
authors.lastname: Vlajkovic
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Hao
authors.initials: H
authors.lastname: Chang
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Song Yee
authors.initials: SY
authors.lastname: Paek
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand ; Section of Audiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Howard H-T
authors.initials: HH
authors.lastname: Chi
authors.affiliation: Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Sreevalsan
authors.initials: S
authors.lastname: Sreebhavan
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand ; Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Ravindra S
authors.initials: RS
authors.lastname: Telang
authors.affiliation: Department of Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Tingle
authors.affiliation: Translational Neuroscience Facility and Department of Physiology, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Housley
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand ; Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand ; Section of Audiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Thorne
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003051:Cochlea / Q000187:drug effects / Q000293:injuries; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy* / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D020011:Protective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020011:Protective Agents; C106045:adenosine amine congener; D000241:Adenosine