Anti-endotoxin actions of methylprednisolone in the isolated perfused cat liver.
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.
D000818:Animals; D002403:Cathepsins / Q000378:metabolism; D002415:Cats; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008247:Lysosomes / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure
D004731:Endotoxins; D007770:L-Lactate Dehydrogenase; D002403:Cathepsins; D008775:Methylprednisolone