Toxicol Appl Pharmacol 1986 Jul;84(3):431-8

Effects of gentamicin on the renal uptake of endogenous and exogenous protein in
conscious rats.

Bernard A, Viau C, Ouled A, Tulkens P, Lauwerys R

To study the effect of gentamicin on the renal uptake of proteins,
Sprague-Dawley female rats were intravenously injected with solutions containing
unlabeled human beta 2-microglobulin (beta 2-m), retinol-binding protein, and
increasing amounts of gentamicin (from 0.063 up to 31.5 mg/kg). The
concentrations of human proteins and that of endogenous beta 2-m, albumin, and
IgG in the urine collected during the 2 hr following the injection were
determined by immunoassays. Gentamicin transiently increased the urinary
excretion of rat and human beta 2-m in a dose-dependent manner. The mean
relative increase of rat beta 2-m excretion ranged from 2 at a gentamicin dose
of 0.06 mg/kg up to 500 at a gentamicin dose of 31.5 mg/kg. By contrast, the
urinary excretion of other proteins was only increased by a factor of 2 to 5 at
the highest dose of gentamicin. The relative increase of the urinary excretion
of proteins was positively correlated with the fractional reabsorption of the
proteins by the rat kidney. The inhibitory effect of gentamicin on the renal
uptake of protein was very similar to that observed in rats injected with
polycationic proteins like lysozyme and cytochrome C. These observations,
combined with the fact that gentamicin, like proteins, enters the tubular cell
by adsorptive endocytosis, strongly suggest that this drug competes with
proteins for common binding sites on the apical tubular membrane and for
subsequent endocytosis. Furthermore, the iv injection of large amounts of
gentamicin and polycationic proteins induces a lysosomal enzymuria which very
likely is a manifestation of an increased exocytosis.

PMID: 3523831, UI: 86262427