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

Authors:
  • MGMichael J. Galvin
    Michael J. Galvin
  • KSKathleen Shupe
    Kathleen Shupe
  • ALAllan M. Lefer
    Allan M. Lefer
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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 microgram/g tissue) to the perfusate did not change perfusion pressure or total oxygen consumption. However, 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 x 10(-3) M) to the perfusion medium prevented the endotoxin-induced changes in hepatocyte integrity. It is suggested that a major action of endotoxin in the liver is 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.

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