Amelioration of aminoglycosideototoxicity by polyanion given through specific routes

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1. Evaluation of aminoglycoside(AG) ototoxicity by binding activities with phosphatidylinositol diphosphate(PIP_2)According to the binding activities between AGs and PIP_2, new products of AGs such as astromicin showed a good coincidence with the binding activities and ototoxic degrees from animal experiments. However, there were few exceptions such as tobramycin and ribostamycin. These results suggested that an evaluation from a viewpoint of binding abilities of AGs with PIP_2 has some limits but important for ototoxicity.2. Ameliorative effect on AGs ototoxicity by polyanion given through the tympanic cavityElevation of the N_1 threshold of action potential measured by the electro-cochleogram was slightly protected in the group given heparin(Hp) and Kanamycin(KM) at the same time. KM ototoxicity was significantly ameliorated in the group of KM application after intratympanic Hp treatment (p<0.001 by t-test). These results were also confirmed by a morphological investigation of a scan … More ning electron microscopy(SEM). KM ototoxicity observed by SEM was significantly reduced in the group given KM and Hp at the same time(p<0.05).3. Ameliorative effect on AGs ototoxicity by polyanion given through the stylomastoid foramenThe cochlear hair cell damages were quantitatively compared in the three different goups, GM(0.4 mg) only group, GM(0.4 mg)and Hp(50 U)at the same group, and GM(0.4 mg) after Hp(50 U) group. there were no significant differences among these three groups. This indicated that stronger binding affinity of AGs wit PIP_2 in the cochlea could not interfered by Hp. Therefore, AGs ototoxicity could not ameliorated.Conclusions were as follows: (1) The binding ability of AGs to the cochlear hair cell is important as a first step of ototoxicity. (2) hp as polyanion could slightly block the binding of them and reduced ototoxicity to some extent. (3) Ameliorative effect on AGs ototoxicity by Hp showed some limits because of the stronger binding ability of PIP_2 than Hp with AGs. Less