Abstract
Certain steroidal and nonsteroidal anti-inflammatory drugs were found to stabilize in vitro lysosomes obtained from a heavy mitochondrial rat liver fraction. Membrane stabilization was measured by determining the effects of drugs on the release of acid phosphatase and β-glucuronidase from lysosomes. Specific experimental conditions were necessary for the measurement of drug-induced stabilization. The 3500 g liver fraction, prepared in a Ten Broeck tissue grinder and incubated at 37° in sucrosetris acetate buffer (pH 7.4) free of sodium ion, was found to be the most suitable source of lysosomes in these studies. Chloroquine, hydrocortisone, acetylsalieylic acid, phenylbutazone, flufenamic acid and niflumic acid exhibited good lysosome membrane-stabilizing activity, while indomethacin showed only moderate activity. Mefenamic acid, ibufenac, gold, Imuran and Cytoxan as well as dozens of drugs from other therapeutic classes were inactive. When lysosomes were incubated in a buffer containing sodium acetate rather than tris acetate or at 45° rather than 37°, anti-inflammatory drugs no longer stabilized but actually enhanced the labilization of lysosomes. The results of these studies indicate that considerable caution must be exercised in the preparation, handling and incubation of lysosomes in order to reveal the stabilizing capacity in vitro of anti-inflammatory drugs.
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