Combined Effect of Aminoglycoside Antibiotic and Potent Diuretics on the Cochlea

Abstract

The study was designed to examine the combined toxic effect of DKB, a new semi-synthetic aminoglycoside antibiotic, and diuretics, ethacrynic acid or furosemide, on the cochlea in three groups of guinea pigs and mice. One group received DKB alone, one received ethacrynic acid or furosemide alone, and one received DKB with either of ethacrynic acid or furosemide. DKB was found as much toxic as kanamycin A, but less toxic than gentamicin with regard to toxicity /g/ body weight. Degeneration appeared first in the outer hair cells in the basal turn of the cochlea starting with the increasing of lyosomes, degeneration of mitochondria and resulting in the complete loss of hair cells, but stria vascularis showed little change.
No change in the cochlea were observed in 2 days after single administration of DKB, ethacrynic acid or furosemide in both guinea pigs and mice. Mice receiving both DKB and diuretics did not show any change in the cochlea.
The harmful effects were shown in guinea pigs, when DKB and ethacrynic acid were combined, more significantly than predicted by simple addition of the effect of each drug. The sever disintegration and loss of outer and inner hair cells and nerve fibers in all turns were observed in this condition. Therefore, it was suggested that a care must be taken when amino glycoside antibiotics and ethacrynic acid are given together in a patient. The toxic mechanism of the interaction of these drugs to the cochlea were discussed from the morphological point of view.