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