In vitro inhibition of lysosomal phospholipases by aminoglycoside antibiotics: a comparative study

Aminoglycosides induce an early and characteristic phospholipidosis in the lysosomes of kidney tubular cells. Inhibition of lysosomal phospholipase activity by gentamicin has been demonstrated in vivo and in vitro. Ten aminoglycosides have been examined for their potency in inhibiting phospholipases A1 and A2. Similar IC50's and IC90's (concentrations causing 50 and 90% inhibition) were found for sisomicin, dibekacin, gentamicin, tobramycin, kanamycin B and netilmicin. Kanamycin A, HABA-dibekacin and amikacin showed increasingly higher IC's. Thus, both the number and the position of amino groups are important. Streptomycin had little effect on phosphatidylcholine hydrolysis. Kinetic studies with gentamicin suggest a competitive type of inhibition. This approach may help for the in vitro screening of less toxic aminoglycosides.