Endotoxin-induced changes of endothelial cell viability and permeability: protective effect of a 21-aminosteroid.
Endotoxic shock results in endothelial cell dysfunction and oedema formation. Endotoxin decreased in a concentration-dependent fashion endothelial cell viability with maximum effects by adding 10 micrograms/ml lipopolysaccharide for 48 h (47 +/- 15% and 22 +/- 2.6% of control cells in the presence or absence of foetal calf serum, respectively). Furthermore, incubation (10 h) with lower concentrations of lipopolysaccharide (1 microgram/ml) significantly increased endothelial cell permeability to 250% compared to control values. The 21-aminosteroid U-74389G (10 microM) prevented the cytotoxic effect of lipopolysaccharide as well as the lipopolysaccharide-induced increase in endothelial cell permeability. By contrast, the glucocorticoid methylprednisolone was less effective even at higher concentrations (100 microM). The effect of lipopolysaccharide is possibly due to oxidative stress and/or membrane destabilization rather than to the induction of inflammatory mediators, because of the reduced efficacy of the glucocorticoid.
Dimmeler
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S
Department of Surgery, University of Cologne, Germany.
Brinkmann
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S
Neugebauer
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E
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D004731:Endotoxins / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000633:toxicity; D008775:Methylprednisolone / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology; D011281:Pregnatrienes / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine; D014810:Vitamin E / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D004731:Endotoxins; D008070:Lipopolysaccharides; D011281:Pregnatrienes; C074965:U 74389F; D014810:Vitamin E; D000493:Allopurinol; D001205:Ascorbic Acid; D008775:Methylprednisolone