Prediction of several new aminoglycosides ototoxicity in vitro

Abstract

First step of aminoglycosides ototoxicity is considered to be electronic binding of basic aminoglycosides (AGs) to acidic phosphatidyl inositol diphosphate. Therefore, competitive binding ability of AGs against basic dyes to acidic glycosaminoglycans was investigated as a predictive method of ototoxicity. The totoluidine blue (TB) method was best among several methods examined so far. Neutral red and alcian blue were employed as new dyes at this experiment, but they were not so good as TB. Furthermore, ototoxicity of the new AGs such as fortimicin, netilmicin, sisomicin, micramicin and habekacin, was predicted by the TB method. However, their predicted ototoxicities were much higher than their results obtained from experimental animals. This indicates that ototoxicity is not produced only by their basicities.