Characterization of aminoglycoside-lipid interactions and development of a refined model for ototoxicity testing
dc.contributor.author | Wang, Barbara M. | en_US |
dc.contributor.author | Weiner, Norman D. | en_US |
dc.contributor.author | Takada, Akira | en_US |
dc.contributor.author | Schacht, Jochen | en_US |
dc.date.accessioned | 2006-04-07T18:18:24Z | |
dc.date.available | 2006-04-07T18:18:24Z | |
dc.date.issued | 1984-10-15 | en_US |
dc.identifier.citation | Wang, Barbara M., Weiner, Norman D., Takada, Akira, Schacht, Jochen (1984/10/15)."Characterization of aminoglycoside-lipid interactions and development of a refined model for ototoxicity testing." Biochemical Pharmacology 33(20): 3257-3262. <http://hdl.handle.net/2027.42/24664> | en_US |
dc.identifier.uri | http://www.sciencedirect.com/science/article/B6T4P-477GFMY-3K/2/7ab707f21d46c6ce68cbcf190e75888e | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/24664 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=6487373&dopt=citation | en_US |
dc.description.abstract | Aminoglycoside interactions with various phospholipids were measured in three model systems and compared with the ototoxicities of the drugs: (a) competition for [14C]neomycin binding; (b) competition for 45Ca2+ binding; and (c) effect on surface pressure of monomolecular lipid films. The efficacies of the antibiotics in displacing neomycin from phosphatidylserine, phosphatidylinositol or phosphatidylinositol bisphosphate were netilmicin > neomycin [ges] gentamicin; the efficacies in displacing calcium from phosphatidylinositol, phosphatidylinositol phosphate or phosphatidylinositol bisphosphate were netilmicin > gentamicin > neomycin > kanamycin > spectinomycin. Neither measure correlated well with the ototoxicities of the drugs which were quantitated at equimolar drug concentrations in cochlear perfusions: neomycin > gentamicin >= tobramycin > netilmicin >= amikacin. When monomolecular films of phosphatidylcholine with phosphatidylserine, cardiolipin, phosphatidylinositol, or phosphatidylinositol phosphate or bisphosphate were challenged with neomycin, the phosphatidylinositol bisphosphate film showed a unique dose-dependent increase in surface pressure while the others showed a decrease or no significant effect. The abilities of aminoglycosides to increase the surface pressure of a film of phosphatidycholine : phosphatidylinositol bisphosphate (1:1 molar ratio) in the presence of 3 mM CaCl2 correlated well with their toxicities. Non-ototoxic cations increased the film pressure or left it unaffected. The results confirm the unique interactions between aminoglycosides and phosphatidylinositol bisphosphate as a possible basis of a mechanism of toxicity and development of a drug-screening system. | en_US |
dc.format.extent | 714755 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.title | Characterization of aminoglycoside-lipid interactions and development of a refined model for ototoxicity testing | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.identifier.pmid | 6487373 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/24664/1/0000077.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1016/0006-2952(84)90087-X | en_US |
dc.identifier.source | Biochemical Pharmacology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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