Amelioration of aminoglycosideototoxicity by polyanion given through specific routes

通过特定途径给予聚阴离子改善氨基糖苷毒性

• 批准号: 61480356
• 负责人: SAITO Hitoshi
• 金额: $ 1.98万
• 依托单位: Fukui Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-61480356/
• 关键词: Aminoglycoside antibiotics; Ototoxicity; Phophatidylinositol diphosphate; Polyanion; Intratympanic application; Stylomastoid foramen application; 軽減効果; アミノ配糖体; フォスフォイノシトール; 試験管内予知法

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

1.通过与磷脂酰肌醇二磷酸(PIP_2)的结合活性评价氨基糖苷(AG)的耳毒性。根据AGs与PIP_2的结合活性，AGs的新产物如阿司米星等与动物实验的结合活性和耳毒性程度有很好的一致性。然而，除了妥布霉素和核糖胺霉素之外，也没有什么例外。这些结果表明，从AGs与PIP_2结合能力的角度来评价AGs有一定的局限性，但对于耳毒性来说是重要的。多聚阴离子鼓室给药对AGs耳毒性的改善耳蜗电测定的动作电位N_1阈值升高在肝素(HP)和卡那霉素(KM)同时给药组略有保护。KM鼓室内Hp治疗后KM耳毒性明显改善(P&lt；0.001，t检验)。这些结果也被扫描…的形态研究所证实更多的是电子显微镜(SEM)。扫描电子显微镜观察KM耳毒性在KM和HP同时给药组明显减轻(P&lt；0.05)。通过茎乳孔给予多聚阴离子对耳蜗毛细胞损伤的改善作用比较GM(0.4 mg)组、GM(0.4 mg)+HP(50U)组、GM(0.4 mg)+HP(50U)组和GM(0.4 mg)+HP(50U)组耳蜗毛细胞损伤程度。三组间差异无统计学意义。这表明HP不能干扰耳蜗内AGs与PIP_2较强的结合亲和力。结论如下：(1)作为耳毒性的第一步，AGs与耳蜗毛细胞的结合能力是重要的。(2)HP作为聚阴离子可轻微阻断它们的结合，并在一定程度上降低耳毒性。(3)由于PIP_2与AGs的结合能力强于Hp，因此Hp对AGs耳毒性的改善作用有限。较少

项目成果

斎藤武久: Ear Research Japan. 19. (1988)

Takehisa Saito：日本耳朵研究 19。（1988）

Takehisa,Saito: "An experimental study on reduction of aminoglycoside ototoxicity by heparin given through specific routes" Ear Research Japan. 19. (1988)

Takehisa，Saito：“通过特定途径给予肝素降低氨基糖苷类耳毒性的实验研究”日本耳研究。

斎藤武久: Ear Research Japan. 18. 16-20 (1987)

Takehisa Saito：日本耳朵研究。18. 16-20 (1987)

Hitoshi,Saito: "In vitro prediction of aminglycoside ototoxicity" Archives of Oto-Rhino-Laryngology. 243. 246-249 (1986)

Hitoshi，Saito：“氨基糖苷耳毒性的体外预测”耳鼻喉学档案。

Hitoshi SAITO: Auris Nasus Larynx. 14. 139-145 (1987)

斋藤仁：Auris Nasus 喉。