Leupeptin and E-64, inhibitors of cysteine proteinases, prevent gentamicin-induced lysosomal phospholipidosis in cultured rat fibroblasts.
(1994) Toxicology Letters — Vol. 73, n° 3, p. 201-208 (1994)
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- 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.
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Montenez, J. P., Maldague, P., Kishore, B. K., & Tulkens, P. M. (1994). Leupeptin and E-64, inhibitors of cysteine proteinases, prevent gentamicin-induced lysosomal phospholipidosis in cultured rat fibroblasts. Toxicology Letters, 73(3), 201-208. https://hdl.handle.net/2078.5/79593 (Original work published 1994)