Protective effect of calcineurin inhibitors on acoustic injury of the cochlea.
This study examined the effect of immunosuppressants, cyclosporin A, FK506 and rapamycin on functional recovery of the cochlea after acoustic overexposure, in guinea pigs and mice. Thirty guinea pigs were exposed to a 2 kHz pure tone at 120 dB SPL for 10 min. The compound action potential threshold shift induced by acoustic overexposure was examined. Twenty-five mice were exposed to a 4 kHz pure tone at 128 dB SPL for 4h. Auditory brainstem response was used to examine the hearing threshold shift. In both the guinea pig and mouse experiments, cyclosporin A and FK506, intraperitonally given just before acoustic overexposure, significantly decreased the hearing threshold shift one or two weeks after acoustic overexposure. However, neither rapamycin nor the FK506 and rapamycin combined treatment groups showed improvement of the threshold shift. The present findings suggest that these two calcineurin inhibitors have a protective effect against acoustic injury of the cochlea, whereas the non-calcineurin inhibitor, rapamycin, not only has no effect against acoustic injury, but rather blocked the effect of FK506. This indicated a possible role of calcineurin against acoustic injury.
Uemaetomari
Isao
I
Department of Otolaryngology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Tabuchi
Keiji
K
Hoshino
Tomofumi
T
Hara
Akira
A
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001301:Audiometry, Pure-Tone / Q000379:methods; D001933:Brain Stem / Q000502:physiology; D065095:Calcineurin Inhibitors; D003051:Cochlea / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D016572:Cyclosporine / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000473:pathology; D006317:Hearing Loss, Noise-Induced / Q000473:pathology / Q000503:physiopathology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D020011:Protective Agents / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology; D013045:Species Specificity; D016559:Tacrolimus / Q000037:antagonists & inhibitors / Q000494:pharmacology
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020011:Protective Agents; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus