A role of glutamate in drug-induced ototoxicity: in vivo microdialysis study combined with on-line enzyme fluorometric detection of glutamate in the guinea pig cochlea

The time course of the changes in perilymphatic glutamate was determined du ring the application of kanamycin and ethacrynic acid, which are known to d amage the hair cells in the inner ear. For the continuous recording of glut amate, the microdialysis technique combined with an enzyme-linked fluoromet ric assay was used. In guinea pigs receiving a loading dose of 800 mg/kg of kanamycin subcutaneously followed 3 h later by an i.v. injection of 40 mg/ kg of ethacrynic acid, a marked glutamate release was clearly found about 2 h after the injection of ethacrynic acid. Injection of kanamycin or ethacr ynic acid alone did not produce any change in the perilymphatic glutamate. The morphological changes induced by the administration of both drugs indic ated that the collapsing hair cells might release glutamate into the perily mphatic space. The present findings provide additional evidence that glutam ate acts as an aggravating factor in aminoglycoside-induced ototoxicity. (C ) 2000 Elsevier Science B.V. All rights reserved.