1: Eur J Pharmacol 1995 Apr 28;289(2):321-33
Aminoglycoside antibiotics induce aggregation but not fusion of negatively-charged
liposomes.
Van Bambeke F, Tulkens PM, Brasseur R, Mingeot-Leclercq MP
Unite de Pharmacologie Cellulaire et Moleculaire, Universite Catholique
de Louvain, Brussels, Belgium.
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.
PMID: 7621906, UI: 95347440