Aminoglycoside antibiotics inhibit lysosomal phospholipase A and C from rat liver in vitro

Accumulation of aminoglycoside antibiotics and phospholipids in lysosomes is a prominent feature of aminoglycoside nephrotoxicity, suggesting the possibility that these agents may inhibit the activity of lysosomal phospholipases. We examined the effect of four aminoglycoside antibiotics, amikacin, dibekacin gentamicin and tobramycin, on the hydrolysis of [3H]dioleoylphosphatidylcholine by a lysosomal protein fraction obtained from rat liver which contains phospholipase A and C. Phospholipase A was inhibited strongly by these agents. Phospholipase C was also inhibited, especially by amikacin and tobramycin. These results suggest that the accumulation of phospholipids in the kidney cortex in aminoglycoside nephrotoxicity may be due to inhibition of lysosomal phospholipase action.