Quantitative approaches to the ototoxicity problem^{1, 2}

This paper describes some of the possible approaches to quantitative evaluation of the biochemical effects of ototoxic agents upon fluids and tissues of the internal ear. Major emphasis is placed upon the ultramicrochemical techniques of Lowry, which offer adequate sensitivity for the quantitative determination of metabolites and enzymes in minutes fluid samples and in microscopic tissue elements and single cells. As specific examples, the effects of ethacrynic acid and of salicylate upon the levels of high energy phosphates in stria vascularis, spiral organ and other internal ear structures are described. In most instances, chemical analyses were preceded by electrophysiological evaluations. Results are compared with those obtained in ischemia and following local application of toxic agents, such as cyanide and dinitrophenol. In respect to the ototoxic effects of aminoglycoside antibiotics, only pilot experiments have been performed to date. Methodological problems are extremely complex in this area. In order to obtain meaningful data, analyses should be performed at a stage when chemical changes are already present, but structural damage is still minimal.