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1 Research department, Pharmaceutical Division, CIBA-GEIGY Corporation, Ardsley, New York
A variety of steroidal and nonsteroidal anti-inflammatory drugs and other therapeutic agents were tested for their capacity to alter in vivo the integrity of rat liver lysosomes. Drugs were administered, either p.o. or i.p. in two doses to fasted rats. The integrity of liver lysosomes was assessed by determining their relative mechanical and osmotic fragility. The degree of redistribution of lysosomal marker enzymes from the sedimentable or bound fraction to the unsedimentable or free fraction, under controlled conditions, was measured. Hydrocortisone, paramethasone, phenylbutazone, oxyphenbutazone, acetylsalicylic acid, indomethacin and flufenamic acid reduced, whereas vitamin A, chlorpromazine and chlorpheniramine accelerated, the redistribution of enzymes to the free fraction. No appreciable action was exhibited by mefenamic acid, cyclophosphamide or dextropropoxyphene. The in vivo data presented in this report support further the hypothesis, heretofore based on in vitro data, that anti-inflammatory drugs inhibit the extrusion of enzymes from lysosomes.
Submitted on December 28, 1971
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