Comparative assessment of poly-L-aspartic and poly-L-glutamic acids as protectants against gentamicin-induced renal lysosomal phospholipidosis, phospholipiduria and cell proliferation in rats.

Coadministration of poly-L-aspartic acid (poly-L-Asp) protects rats against all measured signs of aminoglycoside nephrotoxicity. Based on in vitro and acute in vivo models, previously we hypothesized that poly-L-Asp protects by forming complexes with the drug in lysomes of proximal tubular cells. However, another closely related peptide, poly-L-glutamic acid (poly-L-Glu), could not protect against gentamicin-induced phospholipidosis and nephrotoxicity, presumably because it is susceptible to rapid hydrolysis in sysosomes in vivo.

Distribution of epidermal growth factor in the kidneys of rats exposed to amikacin.

The distribution of epidermal growth factor (EGF) was examined by immunocytochemistry in the kidneys of rats exposed to amikacin, an aminoglycoside antibiotic causing tubular necrosis at high dose. Five-animal groups were treated for 4 or 10 days with amikacin at daily doses of 15, 40, 80 or 200 mg/kg. The drug was delivered i.

Redistribution of epidermal growth factor immunoreactivity in renal tissue after nephrotoxin-induced tubular injury.

Tubular necrosis elicits a process of renal tissue repair characterized by an increase of cell turnover in tubular epithelium. The present study was undertaken to examine the distribution of epidermal growth factor (EGF) and/or of its larger precursor proEGF in the kidney undergoing tubular regeneration. Sprague-Dawley rats were exposed to various drugs (aminoglycosides or platinum-based anticancer agents) known to induce tubular necrosis.

Mechanism of protection afforded by polyaspartic acid against gentamicin-induced phospholipidosis. I. Polyaspartic acid binds gentamicin and displaces it from negatively charged phospholipid layers in vitro.

Coadministration of polyaspartic acid protects rats against aminoglycoside-induced nephrotoxicity, with respect to functional and pathological changes as well as to early signs of renal alterations (lysosomal phospholipidosis of proximal tubular cells, increased proliferation of proximal tubular and peritubular cells), without reduction, but actually by increasing the drug cortical content (Williams et al., J. Pharmacol.