The effects of the glucocorticoid receptor antagonist RU486 and phospholipase A2 inhibitor quinacrine on acoustic injury of the mouse cochlea.
Glucocorticoids are used clinically for the treatment of acoustic injury. However, the protective mechanism of glucocorticoid in acoustic injury has not been completely clarified. Also, the effects of phospholipase A2 (PLA2) on acoustic injury have not been examined to the best of our knowledge. The purpose of the present study was to examine the effects of methylprednisolone, a glucocorticoid receptor inhibitor (RU486) and a phospholipase A2 inhibitor (quinacrine) on cochlear injury induced by acoustic overexposure. Seventy-eight mice were exposed to a 4kHz pure tone at 128dB SPL for 4h. The auditory brainstem response (ABR) was used to examine the hearing thresholds. Cochlear morphology was examined to estimate the outer hair cell loss induced by acoustic overexposure. Methylprednisolone and quinacrine significantly alleviated the hearing threshold shift and hair cell loss induced by acoustic overexposure. RU486 antagonized the protective effect of methylprednisolone. The present findings suggest firstly that glucocorticoids exert protective effects against acoustic injury; secondly, that the protective effect of methylprednisolone was exerted by binding glucocorticoid receptors, and finally that activation of PLA2 may be involved in acoustic injury.
Hirose
Yuki
Y
Department of Otolaryngology, Graduate School of Comprehensive Human Sciences, Majors of Functional and Regulatory Medical Sciences, University of Tsukuba, Tsukuba, Japan.
Tabuchi
Keiji
K
Oikawa
Keiko
K
Murashita
Hidekazu
H
Sakai
Shuhei
S
Hara
Akira
A
D000161:Acoustic Stimulation / Q000009:adverse effects / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D015834:Cochlear Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004347:Drug Interactions; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects; D008775:Methylprednisolone / Q000008:administration & dosage*; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011796:Quinacrine / Q000008:administration & dosage*
D018696:Neuroprotective Agents; D011796:Quinacrine; D008775:Methylprednisolone