Adenosine Amine Congener as a Cochlear Rescue Agent
| Autor: | Peter R. Thorne, Howard H.-T. Chi, R. S. Telang, Malcolm D. Tingle, Song Yee Paek, Srdjan M. Vlajkovic, Gary D. Housley, Hao Chang, Sreevalsan Sreebhavan |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Adenosine Article Subject Hearing loss Adenosine amine congener lcsh:Medicine Protective Agents General Biochemistry Genetics and Molecular Biology Noise exposure Pharmacokinetics Rescue agent Evoked Potentials Auditory Brain Stem otorhinolaryngologic diseases Medicine Animals Rats Wistar Cochlea General Immunology and Microbiology Dose-Response Relationship Drug business.industry lcsh:R General Medicine Adenosine receptor Rats Hearing Loss Noise-Induced Anesthesia Injections Intravenous medicine.symptom business Injections Intraperitoneal medicine.drug Research Article |
| Zdroj: | BioMed Research International, Vol 2014 (2014) BioMed Research International |
| ISSN: | 2314-6141 2314-6133 |
| Popis: | We have previously shown that adenosine amine congener (ADAC), a selective A1adenosine 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.Conclusion. 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. |
| Databáze: | OpenAIRE |
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