Abstract
Noise-induced hearing loss (NIHL) is a global health problem affecting over 5% of the population worldwide. We have shown previously that acute noise-induced cochlear injury can be ameliorated by administration of drugs acting on adenosine receptors in the inner ear, and a selective A1 adenosine receptor agonist adenosine amine congener (ADAC) has emerged as a potentially effective treatment for cochlear injury and resulting hearing loss. This study investigated pharmacokinetic properties of ADAC in rat perilymph after systemic (intravenous) administration using a newly developed liquid chromatography-tandem mass spectrometry detection method. The method was developed and validated in accordance with the USA FDA guidelines including accuracy, precision, specificity, and linearity. Perilymph was sampled from the apical turn of the cochlea to prevent contamination with the cerebrospinal fluid. ADAC was detected in cochlear perilymph within two minutes following intravenous administration and remained in perilymph above its minimal effective concentration for at least two hours. The pharmacokinetic pattern of ADAC was significantly altered by exposure to noise, suggesting transient changes in permeability of the blood-labyrinth barrier and/or cochlear blood flow. This study supports ADAC development as a potential clinical otological treatment for acute sensorineural hearing loss caused by exposure to traumatic noise.
Highlights
Hearing loss is a growing health problem affecting 360 million people worldwide
In 2010, we demonstrated for the first time that the postexposure administration of selective A1 adenosine receptors (A1AR) agonists (2-chloro-N6cyclopentyladenosine and adenosine amine congener) could ameliorate Noise-induced hearing loss (NIHL) in rats [8, 10]
The present study demonstrates that the concentration of adenosine amine congener (ADAC) in the cochlea after 2 hours is still higher than minimum effective concentration (MEC) for this drug, suggesting that the cochlea can maintain the therapeutic concentrations of ADAC for at least 2 h after intravenous administration
Summary
Hearing loss is a growing health problem affecting 360 million people worldwide. Disabling hearing loss refers to hearing loss greater than 40 dB in the better hearing ear in adults and a hearing loss greater than 30 dB in the better hearing ear in children [1]. Noise-induced hearing loss (NIHL) is caused by exposure to high intensity impulse noise or prolonged exposure to moderate or high levels of noise. Hearing loss (measured as auditory threshold shift) may be temporary (TTS), if a repair mechanism is able to restore the organ of Corti or permanent (PTS) when the sensory hair cells or auditory neurons die. Exposure to continuous or impulse noise can cause mechanical damage and metabolic disruptions in the cochlea of the inner ear [4, 5]. Other mechanisms of NIHL include glutamate excitotoxicity, Ca2+ overload in sensory hair cells, inflammation, ischemia/reper fusion injury, and cochlear synaptopathy [5, 7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
