In vitro response of hepatic lysosomes to endogenous and exogenous cationic compounds

An investigation of the effect of four cationic compounds on rat liver lysosomes was carried out. Lysosomes from homogenized rat liver were isolated by differential centrifugation at 0-5 degrees C in 0.3 M sucrose. These lysosomes were then incubated for 1 hr at 37 degrees C in 0.25 M glycine solution containing widely varied concentrations of the test agent. The lysosomes were resedimented and the N-acetyl-beta-glucosaminidase (NAG) activity was measured in the supernatant and in the remaining pellet after disruption. Spermine, ferric ion, mepacrine, and gentamicin all produced dose-dependent effects on these lysosomes. Low concentrations of these compounds inhibited the release of NAG into the supernatant while high concentrations enhanced the release of NAG. This effect of these cationic compounds on the lysosomal membrane may be a mechanism by which they produce cellular toxicity with the organ or tissue selectivity being related to the distribution of the cation.