1: J Antimicrob Chemother 1998 Dec;42(6):761-7
Lysosomal alterations induced in cultured rat fibroblasts by long-term
exposure to low concentrations of azithromycin.
Van Bambeke F, Gerbaux C, Michot JM, d'Yvoire MB, Montenez JP, Tulkens
PM
Unite de Pharmacologie Cellulaire et Moleculaire, Uinversite Catholique
de Louvain, Brussels, Belgium. vanbambeke@facm.ucl.ac.be
Computer-aided simulations suggest that the doses and schedules of administration
of azithromycin proposed in treatment and prophylaxis of Mycobacterium
avium complex (MAC) in AIDS patients will result in drug concentrations
in serum and extracellular fluids remaining for sustained periods of time
in the 0.03-0.1 mg/L range. We exposed cultured rat embryo fibroblasts
to these concentrations (and multiples up to 20 mg/L) for up to 16 days.
Electron microscopy showed that after 7 days' incubation in 0.03 mg/L azithromycin,
there was conspicuous accumulation of osmiophilic, lamellar structures
(myeloid bodies) in lysosomes, suggesting the onset of a phospholipidosis.
Assay of total cell phospholipids and cholesterol showed significant increases
in cells exposed to > or = 1 to 5 mg/L of azithromycin in association with
hyperactivity of the lysosomal enzyme cathepsin B. The data suggest that
azithromycin, at extracellular concentrations pertinent to its use for
MAC treatment, and perhaps also prophylaxis, causes limited morphological
alterations of the lysosomes in cultured cells which are of the same nature
as those developing rapidly and extensively at higher concentrations.
PMID: 10052900, UI: 99160265