Low-dose, long-term caroverine administration attenuates impulse noise-induced hearing loss in the rat.
CONCLUSIONS
Physiological and morphological assessments indicated that low-dose and long-term caroverine delivery might be a new approach to protect against impulse noise-induced hearing loss.


BACKGROUND
Although the exact mechanisms by which impulse noise causes hearing loss are still unclear, there is accumulating evidence that increased reactive oxygen species (ROS) production and excessive glutamate released from the inner hair cells lead to hair cell loss and consequently hearing loss. Caroverine is an antagonist of two glutamate receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the inner ear, as well as an antioxidant.


METHODS
In this study, caroverine was delivered subcutaneously using an osmotic pump. This kind of delivery has the advantage, via continuous, long-term and low dose drug administration, of avoiding systemic side effects.


RESULTS
It was shown that caroverine could significantly protect the cochlea against impulse noise trauma.
Duan
Maoli
M
Center for Hearing and Communication Research, Karolinska Hospital, SE-17 176 Stockholm, Sweden. maoli.duan@cfh.ki.se
Chen
Zhiqiang
Z
Qiu
Jianxin
J
Ulfendahl
Mats
M
Laurell
Göran
G
Borg
Erik
E
Ruan
Runsheng
R
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001305:Auditory Fatigue / Q000187:drug effects / Q000502:physiology; D001933:Brain Stem / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000502:physiology; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006317:Hearing Loss, Noise-Induced / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007279:Injections, Subcutaneous; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology
D000975:Antioxidants; D011810:Quinoxalines; D017382:Reactive Oxygen Species; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C000957:caroverine