Effect of anti-inflammatory drugs on lysosomes and lysosomal enzymes from rat liver

Steroidal and nonsteroidal anti-inflammatory drugs were tested for their capacity to stabilize, in vitro, lysosomes and inhibit lysosomal enzymes. Lysosome membrane stability was measured by determining the effects of drugs on the release of aryl sulfatase and β-glucuronidase from lysosomes which were suspended in a hypo-osmotic sucrose buffer. Lysosomes obtained from a heavy mitochondrial (3500 g) rat liver fraction were found to be highly sensitive to membrane stabilization by naproxen, alclofenac, chloroquine, mefenamic acid, phenylbutazone, hydrocortisone, dexamethasone and methylprednisolone. Ibuprofen and flufenamic acid demonstrated moderate stabilizing activity, while indo-methacin, aspirin and clonixin showed only weak activity. Imuran, as well as other anti-inflammatory drugs, was inactive. In addition to their membrane-stabilizing activity, chloroquine was found to be a potent inhibitor of aryl sulfatase and phenylbutazone an inhibitor of β-glucuronidase activity. Hydrocortisone, dexamethasone and paramethasone inhibited aryl sulfatase activity, while no steroid tested was effective as an inhibitor of β-glucuronidase. The data in this report support the hypothesis that anti-inflammatory drugs inhibit the release of enzymes from lysosomes. In addition, several of these drugs may act as inhibitors of lysosomal enzyme activity.