Jp. Montenez et al., LEUPEPTIN AND E-64, INHIBITORS OF CYSTEINE PROTEINASES, PREVENT GENTAMICIN-INDUCED LYSOSOMAL PHOSPHOLIPIDOSIS IN CULTURED RAT FIBROBLASTS, Toxicology letters, 73(3), 1994, pp. 201-208
Aminoglycoside antibiotics, such as gentamicin, cause an early lysosom
al phospholipidosis in the renal cortex, which is considered as a key
event in the onset of acute tubular necrosis induced by these drugs. I
n a model of primary cultures of embryonic rat fibroblasts which devel
op typical lysosomal phospholipidosis when incubated with gentamicin (
decrease of sphingomyelinase activity; increase in total cells lipid p
hosphorus; appearance of so-called 'myeloid bodies' in lysosomes), we
observed a protective effect exerted by inhibitors of cysteine protein
ases (leupeptin, E-64) against this alteration on the basis of both bi
ochemical and morphological criteria. Actually leupeptin and E-64 caus
ed a marked stimulation of sphingomyelinase activity both in control a
nd in gentamicin-treated cells, which we suggest to be the cause of pr
otection.