Open AccessMembrane perturbation by aminoglycosides as a simple screen of their toxicity
Author(s) -
S. Au,
Norman Weiner,
Jochen Schacht
Publication year - 1986
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.30.3.395
Subject(s) - aminoglycoside , ototoxicity , netilmicin , chemistry , toxicity , neomycin , pharmacology , phosphatidylinositol , gentamicin , tobramycin , biochemistry , biology , medicine , surgery , antibiotics , chemotherapy , organic chemistry , kinase , cisplatin
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.