Inhibition of tumor necrosis factor-alpha release in rat experimental endotoxemia by treatment with the 21-aminosteroid U-74389G.
OBJECTIVE
To determine the effect of the 21-aminosteroid U-74389G on tumor necrosis factor (TNF)-alpha release in experimental endotoxemia.


METHODS
Prospective, randomized, controlled animal study.


METHODS
Experimental laboratory.


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


METHODS
The rats were divided equally into 3 groups: a) control; b) endotoxemia (5 mg/kg lipopolysaccharide [LPS] from Escherichia coli 055:B5); and c) endotoxemia and U-74389G administration 30 mins before (3 mg/kg) and 60 mins after (1.5 mg/kg) endotoxin challenge.


RESULTS
At 0, 120, and 240 mins, serum levels of TNF-alpha were measured using a specific rat TNF-alpha ELISA kit. U-74389G-treated endotoxemic animals showed significantly reduced TNF-alpha release 120 mins after endotoxin challenge (control, 2.5+/-2.1 pg/mL; LPS, 4041+/-871 pg/mL; U-74389G, 1627+/-474 pg/mL [p < .05]). Two hundred forty minutes after LPS administration, TNF-alpha levels decreased, whereas values in the untreated LPS group remained twice as high as those in the U-74389G group (LPS, 863+/-182 pg/mL; U-74389G, 369+/-54 pg/mL [p < .05]).


CONCLUSIONS
The study demonstrated that administration of U-74389G, which has radical-scavenging and membrane-stabilizing properties, decreased TNF-alpha release during endotoxemia. Thus, 21-aminosteroids may lend themselves to evaluation in the treatment of septic states.
Lehmann
C
C
Department of Anaesthesiology and Intensive Care, University Hospital Charité, Humboldt University, Berlin, Germany.
Egerer
K
K
Georgiew
A
A
Weber
M
M
Grune
T
T
Kox
W J
WJ
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D019446:Endotoxemia / Q000188:drug therapy* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011281:Pregnatrienes / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000975:Antioxidants; D008070:Lipopolysaccharides; D011281:Pregnatrienes; D014409:Tumor Necrosis Factor-alpha; C074965:U 74389F; D008315:Malondialdehyde