Reduction in intestinal leukocyte adherence in rat experimental endotoxemia by treatment with the 21-aminosteroid U-74389G.
OBJECTIVE
To investigate leukocyte adherence in intestinal venules in experimental endotoxemia after treatment with the 21-aminosteroid U-74389G.


METHODS
Prospective, randomized, controlled animal study in an experimental laboratory.


METHODS
Twenty-one male Wistar rats weighing 190 +/- 40 g.


METHODS
The rats were divided equally into three groups: (a) control group, (b) endotoxemia (5 mg/kg lipopolysacharide from Escherichia coli O55:B5), and (c) endotoxemia and U-74389G administration 30 min before (3 mg/kg) and 60 min after endotoxin challenge (1.5 mg/ kg).


RESULTS
The distal small intestine of the animals was examined using intravital fluorescence videomicroscopy 2 h after endotoxin challenge. Leukocytes were stained in vivo by means of rhodamine 6G. In the endotoxemic animals we observed a fourfold increase in the count of firmly adherent leukocytes in submucosal post-capillary and collecting venules. Treatment with the 21-aminosteroid U-74389G significantly attenuated the count of sticking leukocytes in the collecting venules (control, 61 +/- 10 cells/mm2; lipopolysaccharide, 237 +/- 42 cells/mm2; U-74389G 125 +/- 9 cells/mm2; p < 0.05). In these venules leukocyte rolling behavior was comparable to that in the control group without endotoxin challenge.


CONCLUSIONS
Administration of U-74389G, which has radical scavenging properties, attenuates leukocyte adherence in selected populations of intestinal venules which is found increased during endotoxemia. Thus, 21-aminosteroids may have an impact in the treatment of endotoxin-induced intestinal injury.
Klinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Charité, Humboldt Universität, Berlin, Germany. christian.lehmann@rz.hu-berlin.de
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Lehmann
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Georgiew
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Weber
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Birnbaum
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Kox
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D004731:Endotoxins / Q000633:toxicity; D005609:Free Radicals / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D007421:Intestine, Small / Q000098:blood supply / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008642:Mesenteric Veins / Q000187:drug effects* / Q000276:immunology; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D011281:Pregnatrienes / Q000494:pharmacology*; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014115:Toxemia / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology
D000975:Antioxidants; D004731:Endotoxins; D005609:Free Radicals; D011281:Pregnatrienes; D017382:Reactive Oxygen Species; C074965:U 74389F