The roles of glucocorticosteroid and of fibrinolytic activity in the development of bilateral renal cortical necrosis in cycloheximide-treated mice challenged with a submicrogram dose of endotoxin.
Mice given cycloheximide and 0.2 microgram of endotoxin simultaneously developed ischaemic bilateral renal cortical necrosis as part of a fatal syndrome. Endotoxin given 2 h after cycloheximide, although fatal, failed to produce renal cortical necrosis. Investigation suggested that, following endotoxin challenge in cycloheximide-treated mice, the occurrence or non-occurrence of bilateral renal cortical necrosis was determined by the concentration of circulating glucocorticoids at the time of endotoxin challenge. Thus, below a certain, as yet undefined, glucocorticoid concentration, endotoxin does not cause renal cortical necrosis in cycloheximide-treated mice. Inhibition of the fibrinolytic system by epsilonaminocaproic acid (EACA) indicated that protection against renal cortical necrosis was directly mediated by increased fibrinolytic activity. Since this increased activity occurred during a period of profound cycloheximide-mediated inhibition of protein synthesis, it was postulated that pre-existing plasminogen activator was released from inhibition, and that this release could only occur when the glucocorticoid concentration fell below a certain critical value.
Department of Human Anatomy and Cell Biology, The University, Liverpool, U.K.
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Parry
D015119:Aminocaproic Acid / Q000494:pharmacology; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology*; D004731:Endotoxins / Q000633:toxicity*; D005342:Fibrinolysis; D006854:Hydrocortisone / Q000494:pharmacology*; D007672:Kidney Cortex / Q000098:blood supply / Q000473:pathology; D007673:Kidney Cortex Necrosis / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D013997:Time Factors
D004731:Endotoxins; D003513:Cycloheximide; D015119:Aminocaproic Acid; D006854:Hydrocortisone