Effect of Endotoxin-Tolerance, Cortisone, and Thorotrast on Release of Enzymes from Subcellular Particles of Mouse Liver.

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Abstract
Summary Carbon tetrachloride-induced leakage of 2 acid-hydrolases from mouse liver lysosomes, in vitro, was inhibited by chronic pretreatment of the mice with endotoxin. Cortisone-pretreatment inhibited the release of one of the enzymes. Pretreatment of the mice with Thorotrast, a reticulo-endothelialblocking agent which neutralizes tolerant states, had the opposite effect and caused accelerated release of acid-hydrolases from liver lysosomes of tolerant as well as normal animals. None of the 3 agents studied produced comparable changes in the rate of leakage of soluble dehydrogenases from mouse liver mitochondria. It is suggested that stabilization of hepatic lysosomal membranes in endotoxin-tolerant animals represents a selective response of these particles to repeated small doses of the toxin and plays an important role in the development of tolerance to this agent.