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Role of peptide leukotrienes and their hepatobiliary elimination in endotoxin action.
Circ Shock. 1984; 14(4):223-35.CS

Abstract

The lethal action of endotoxin was studied in mice sensitized against the lipopolysaccharide by D-galactosamine. Protection was obtained by FPL 55712, a selective antagonist of sulfidopeptide leukotrienes, by diethylcarbamazine, an inhibitor of leukotriene biosynthesis, by BW 755C, a dual lipoxygenase and cyclooxygenase inhibitor, and by dexamethasone, which inhibits arachidonate release. Indomethacin incompletely antagonized endotoxin lethality; indoprofen did not protect at all. Leukotriene generation induced by endotoxin in vivo could be demonstrated in rats by employing a radioimmunoassay on bile extracts since intravascular sulfidopeptide leukotrienes were rapidly eliminated into bile. Additionally, however, endotoxin affected the hepatobiliary elimination of sulfidopeptide leukotrienes. From intravenously injected tracer [3H]leukotriene D4, 67% appeared only partially metabolized in bile within 30 min in control rats. Endotoxin and lipid A reduced the biliary [3H]leukotriene D4 secretion by up to 80% while enhancing the hepatic [3H]leukotriene D4 content up to twofold. This inhibition of hepatobiliary elimination was stronger than endotoxin-induced reductions of bile flow or of biliary [14C]taurocholate secretion. Endotoxin, as an activator of the arachidonate cascade, thus potentiates its action in vivo by interfering with the rapid hepatobiliary clearance of sulfidopeptide leukotrienes in addition to stimulating leukotriene and prostanoid formation.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

6096038

Citation

Hagmann, W, et al. "Role of Peptide Leukotrienes and Their Hepatobiliary Elimination in Endotoxin Action." Circulatory Shock, vol. 14, no. 4, 1984, pp. 223-35.
Hagmann W, Denzlinger C, Keppler D. Role of peptide leukotrienes and their hepatobiliary elimination in endotoxin action. Circ Shock. 1984;14(4):223-35.
Hagmann, W., Denzlinger, C., & Keppler, D. (1984). Role of peptide leukotrienes and their hepatobiliary elimination in endotoxin action. Circulatory Shock, 14(4), 223-35.
Hagmann W, Denzlinger C, Keppler D. Role of Peptide Leukotrienes and Their Hepatobiliary Elimination in Endotoxin Action. Circ Shock. 1984;14(4):223-35. PubMed PMID: 6096038.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of peptide leukotrienes and their hepatobiliary elimination in endotoxin action. AU - Hagmann,W, AU - Denzlinger,C, AU - Keppler,D, PY - 1984/1/1/pubmed PY - 1984/1/1/medline PY - 1984/1/1/entrez SP - 223 EP - 35 JF - Circulatory shock JO - Circ Shock VL - 14 IS - 4 N2 - The lethal action of endotoxin was studied in mice sensitized against the lipopolysaccharide by D-galactosamine. Protection was obtained by FPL 55712, a selective antagonist of sulfidopeptide leukotrienes, by diethylcarbamazine, an inhibitor of leukotriene biosynthesis, by BW 755C, a dual lipoxygenase and cyclooxygenase inhibitor, and by dexamethasone, which inhibits arachidonate release. Indomethacin incompletely antagonized endotoxin lethality; indoprofen did not protect at all. Leukotriene generation induced by endotoxin in vivo could be demonstrated in rats by employing a radioimmunoassay on bile extracts since intravascular sulfidopeptide leukotrienes were rapidly eliminated into bile. Additionally, however, endotoxin affected the hepatobiliary elimination of sulfidopeptide leukotrienes. From intravenously injected tracer [3H]leukotriene D4, 67% appeared only partially metabolized in bile within 30 min in control rats. Endotoxin and lipid A reduced the biliary [3H]leukotriene D4 secretion by up to 80% while enhancing the hepatic [3H]leukotriene D4 content up to twofold. This inhibition of hepatobiliary elimination was stronger than endotoxin-induced reductions of bile flow or of biliary [14C]taurocholate secretion. Endotoxin, as an activator of the arachidonate cascade, thus potentiates its action in vivo by interfering with the rapid hepatobiliary clearance of sulfidopeptide leukotrienes in addition to stimulating leukotriene and prostanoid formation. SN - 0092-6213 UR - https://www.unboundmedicine.com/medline/citation/6096038/Role_of_peptide_leukotrienes_and_their_hepatobiliary_elimination_in_endotoxin_action_ DB - PRIME DP - Unbound Medicine ER -