Effects of Ototoxic Diuretics (Loop Diuretics) on the Endolymphatic Sac

Abstract

The acute and chronic effects of treatment with ethacrynic acid (EA) and furosemide (FU) on the structure of the murine endolymphatic sac were studied by means of light and transmission electron microscopy. The animals were treated with loop diuretics in doses which are known to cause morphological alterations of the stria vascularis and a significant reduction of the endocochlear potential. A single intravenous injection of either EA or FU resulted in immediate morhpological changes such as an increase in cytoplasmic contents of endoplasmic reticulum and more prominent Golgi structures of the light cells. These cells developed membrane-bound granules and a smooth tubular network in the apical cytoplasm. These findings together with the appearance of a precipitate on the luminal aspect of the cell membrane suggested secretory activity. Ten days after daily intraperitoneal injections with loop diuretics in sub toxic doses, the epithelial cytoarchitecture of the endolymphatic sac was altered, with pronounced veiling of the light cells by the dark cells. It is concluded that the changes in the endolymphatic sac epithelium after treatment with ototoxic diuretics may not be a result of a primary toxic effect on the sac per se, but rather be secondary to alterations in fluid and ion homeostasis in the rest of the inner ear.

Does severe water deprivation affect the inner ear?

“…It can be suggested that their modified shape could be induced by the increased imbibition of the subepithelial tissue which, for this reason, tends to exert a pressure on the nearby-located structures. An increased looseness of the perisaccular tissue was also observed after ethacrynic acid treatment, thus confirming the results of Erwall et al (1988). Moreover, an increased concentration of an organic matrix located subepithelially was also observed.…”

Correlations between Serum Osmolality and Endolymphatic Sac Response Using Hypertonic Glycerol

“…Earlier studies have revealed similar ES changes after surgical labyrinthectomy [12] and in mice with hereditary type of cochleosaccular degeneration [13] as well as after administration of loop diuretics [14], In addition, installation of hypertonic hyaluronan in the middle ear results in an increased num ber of granular cells in the ES suggestive of an increased secretory activity [ 15]. This was interpreted as an effect of the hyperosmotic agent attracting water from the inner ear.…”