Anti-Endotoxin Actions of Methylprednisolone in the Isolated Perfused Cat Liver

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Abstract
The efficacy of the synthetic glucocorticoid, methylprednisolone, was examined in vitro using an isolated cat liver perfused with a blood-free medium. Addition of endotoxin (75 .mu.g/g tissue) to the perfusate did not change perfusion or total O2 consumption. Cellular integrity was severely compromised, as reflected by increases in perfusate lactate dehydrogenase and cathepsin D activities, increases in tissue lysosomal fragility, and enlargement and vacuolization of lysosomes. Addition of methylprednisolone (1 .times. 10-3 M) to the perfusion medium prevented the endotoxin-induced changes in hepatocyte integrity. A major action of endotoxin in the liver may be to increase lysosomal fragility and the protective action of methylprednisolone appears to be related to its lysosomal stabilizing action. The potent anti-endotoxin action of glucocorticoids in vivo may be due in part to the stabilization of lysosomal membranes in tissues such as the liver.