[en] The binding of aminoglycoside antibiotics to acidic phospholipids of membranes is
an essential step in the development of both their renal and auditory toxicities,
which could be associated with critical modifications of the membrane properties.
This work examines the capacity of aminoglycosides to induce membrane aggregation
and fusion. Three techniques were used in parallel: (i) measurement of the
dequenching rate of a lipid-soluble fluorescent probe (octadecylrhodamine B)
incorporated at self-quenched concentration in membranes; (ii) measurement of the
increase in the energy transfer between two fluorescent derivatives of
phospholipids; and (iii) electron microscopy of negatively-stained replicas. The
results were compared with those obtained with spermine (an aggregating
polycation) and melittin (a fusogenic peptide). The three approaches indicate
that aminoglycosides induce liposomes aggregation, but not fusion. Aggregation is
related to the capacity of each drug studied to bind phosphatidylinositol, as
evaluated by its energy of interaction with this acidic phospholipid, and to its
toxic potential. Membrane aggregation occurring in vivo could therefore
contribute to, or be a determinant of this toxicity, which could rationally be
screened for new derivatives by the methods applied here.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Vanbambeke, F.
Tulkens, Pm.
Brasseur, Robert ; Université de Liège - ULiège > Gembloux Agro-Bio Tech
Mingeot-Leclercq, Marie-Paule
Language :
English
Title :
Aminoglycoside Antibiotics Induce Aggregation But Not Fusion Of Negatively-Charged Liposomes
Publication date :
1995
Journal title :
European Journal of Pharmacology. Molecular Pharmacology Section
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