Au S, Weiner N, Schacht J
Antimicrob Agents Chemother. 1986 Sep;30(3):395-7. doi: 10.1128/AAC.30.3.395.
A simple test to assess the toxicity of aminoglycosides was designed based on the interaction of these drugs with phosphatidylinositol bisphosphate. The fluorescent probe 1-anilino-8-naphthalene sulfonate was incorporated into liposomes composed of L-alpha-phosphatidylcholine and phosphatidylinositol bisphosphate (4:1 molar ratio), and changes in fluorescence induced by the aminoglycosides were measured. The magnitude of these changes correlated well with the intrinsic ototoxicity of the drugs previously established in cochlear perfusions: neomycin greater than gentamicin approximately equal to tobramycin greater than amikacin approximately equal to kanamycin approximately equal to netilmicin greater than neamine approximately equal to spectinomycin. Correlations were not accurate when other phospholipids were substituted for phosphatidylinositol bisphosphate. An alternative in vitro test, measurement of the zeta potential of liposomes, ranked the drugs according to their electrostatic charge but not their toxicity. These results suggest that: a simple screen for aminoglycoside toxicity can be established and perturbation of membranes containing phosphatidylinositol bisphosphate is a key step in aminoglycoside ototoxicity.
基于氨基糖苷类药物与磷脂酰肌醇二磷酸的相互作用，设计了一种评估其毒性的简单测试。将荧光探针1-苯胺基-8-萘磺酸盐掺入由L-α-磷脂酰胆碱和磷脂酰肌醇二磷酸（摩尔比4:1）组成的脂质体中，并测量氨基糖苷类药物诱导的荧光变化。这些变化的幅度与先前在耳蜗灌注中确定的药物内在耳毒性密切相关：新霉素大于庆大霉素约等于妥布霉素大于阿米卡星约等于卡那霉素约等于奈替米星大于新霉素B约等于壮观霉素。当用其他磷脂替代磷脂酰肌醇二磷酸时，相关性不准确。另一种体外测试，即测量脂质体的ζ电位，根据药物的静电荷而非毒性对药物进行排名。这些结果表明：可以建立一种简单的氨基糖苷类毒性筛选方法，含有磷脂酰肌醇二磷酸的膜的扰动是氨基糖苷类耳毒性的关键步骤。
