Ototoxic Effects of Nitrogen Mustard N Oxide, Gentamicin and Ethacrynic Acid and Some Congenital Deaf Animal Cochlea

Abstract

The ototoxic action of nitrogen mustard N oxide, gentamicin and ethacrynic acid on guinea pig and mice was studied. Shaker-l-mice and Hedlund white mink cochlea were also studied with the comparison of drug intoxicated cochlea.
NM was found to be more toxic than kanamycin, streptomycin and gentamicin with regard to their dosages. Toxic reactions were mainly observed in the cochlear sensory epithelia. Degeneration appeared first in the outer hair cells in the basal turn of the cochlea starting with the formation of whorls and proliferation of smooth endoplasmic reticula and ending with the complete degeneration of the sensory cells, but the stria vascularis showed little change. Even after the disappearance of the hair cells, some efferent nerve endings were still present in the organ of Corti.
Ototoxic reactions of gentamicin were first appeared in the mitochondria in the cochlear sensory epithelia, but the stria vascularis showed little change as was observed in NM intoxication. On the other hand, severe changes of the stria vascularis were found in case of ethacrynic acid administration.
Shaker 1 mice have a fairly normal stria vascularis with normal filling of scala media but show severe degeneration of organ of Corti. This cochlea shows pathological changes somewhat similar to those of ototoxic antibiotics intoxicated cochlea. On the other hand, Hedlund white mink showed the degeneration of the organ of Corti caused by severe degeneration of the stria vascularis and collapse of scala media.
We have demonstrated similar final cochlear degeneration following different pathological pathways in five species of animals.