1: Toxicol Lett 1994 Sep;73(3):201-8

Leupeptin and E-64, inhibitors of cysteine proteinases, prevent
gentamicin-induced lysosomal phospholipidosis in cultured rat fibroblasts.

Montenez JP, Kishore BK, Maldague P, Tulkens PM

Unite de Pharmacologie Cellulaire et Moleculaire, Universite Catholique de
Louvain, Brussels, Belgium.

Aminoglycoside antibiotics, such as gentamicin, cause an early lysosomal
phospholipidosis in the renal cortex, which is considered as a key event in the
onset of acute tubular necrosis induced by these drugs. In a model of primary
cultures of embryonic rat fibroblasts which develop typical lysosomal
phospholipidosis when incubated with gentamicin (decrease of sphingomyelinase
activity; increase in total cells lipid phosphorus; appearance of so-called
'myeloid bodies' in lysosomes), we observed a protective effect exerted by
inhibitors of cysteine proteinases (leupeptin, E-64) against this alteration on
the basis of both biochemical and morphological criteria. Actually leupeptin and
E-64 caused a marked stimulation of sphingomyelinase activity both in control
and in gentamicin-treated cells, which we suggest to be the cause of protection.

PMID: 8091428, UI: 94378233