In vitro formation of ω-oxidized metabolites of leukotriene C4 in the rat

Örning, Lars; Keppler, Andrea; Midtvedt, Tore; Hammarström, Sven

doi:10.1016/0090-6980(88)90025-1

Cited by 13 publications

(3 citation statements)

References 11 publications

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“…There is ample information on the metabolism and systemic elimination of cysteinyl LTs in vivo, which occurs predominantly via the hepatobiliary system [15][16][17][18][19][20][21][22][23][24][25][26][27][28]. In contrast, corresponding evidence on the metabolic fate of LTB4 in vivo is scarce [29], and the impact of any hepatobiliary contribution to LTB4 elimination is unknown.…”

Section: Introductionmentioning

confidence: 99%

Hepatic uptake and metabolic disposition of leukotriene B4 in rats

Hagmann

Körte

1990

Biochemical Journal

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1. In isolated perfused rat liver and in vivo, up to 25 % of [3H]leukotriene B4 was eliminated from the circulation via hepatic uptake and biliary excretion within 1 h. Total body recovery of 3H amounted to about 60 % of infused [3H]leukotriene B4. 2. Hepatobiliary excretion of leukotriene B4 and its metabolites exceeded renal elimination by about 4-fold and depended, in contrast with excretion of cysteinyl leukotriene E4, upon continuous taurocholate supply. 3. Analyses of bile, liver and recirculated perfusate using h.p.l.c. indicated that the liver metabolized leukotriene B4 extensively to wocarboxyleukotriene B4 and its f-oxidized derivatives, and no unmetabolized leukotriene B4 appeared in bile. These results substantiate the important contribution of the hepatobiliary system with respect to the metabolic fate of leukotriene B4.

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Section: Introductionmentioning

confidence: 99%

Hepatic uptake and metabolic disposition of leukotriene B4 in rats

Hagmann

Körte

1990

Biochemical Journal

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“…Metabolism of cysteinyl LTs in the liver includes intravascular formation of LTD4 and LTE4 [24] and proceeds in rat hepatocytes to LTE4NAc [2,19,27] and its wo-oxidation products, w-hydroxy-LTE4NAc and co-carboxy-LTE4NAc [4,24,28,[44][45][46][47]. While LTC4 [24] and LTD4 can pass from the circulation via hepatocytes into bile partially unmetabolized (Figs.…”

Section: Discussionmentioning

confidence: 99%

“…The contribution of the liver to cysteinyl LT uptake and metabolism has been studied in rats in vivo, mainly with LTC4 [1,13,14,[17][18][19]27,28], using hepatocytes and hepatoma cells in vitro [29,30], and recently also in the isolated perfused liver [24]. Therefore, the first objective of the present study was to monitor the distribution and metabolic pathways of LTC4 as compared with its metabolites LTD4, LTE4 and N-acetyl- LTE4 (LTE4NAc) in the isolated perfused liver.…”

Section: Introductionmentioning

confidence: 99%

Uptake, production and metabolism of cysteinyl leukotrienes in the isolated perfused rat liver. Inhibition of leukotriene uptake by cyclosporine

Hagmann

Parthé

Kaiser

1989

Biochemical Journal

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1. The isolated perfused rat liver efficiently takes up cysteinyl leukotrienes (LTs) C4, D4, E4 and N-acetyl-LTE4 from circulation. More than 70% of these cysteinyl LTs are excreted from liver into bile within 1 h of onset of a 5 min infusion, while about 5% remain in the liver. About 20% of infused N-acetyl-LTE4 escapes hepatic first-pass extraction under our conditions. 2. Metabolites of LTC4 appearing in bile within 20 min of the onset of infusion include mainly LTD4 and N-acetyl-LTE4, but also omega-hydroxy-N-acetyl-LTE4 and omega-carboxy-N-acetyl-LTE4. Metabolites generated from omega-carboxy-N-acetyl-LTE4 by beta-oxidation from the omega-end represent the major biliary LTs secreted at later times. 3. Stimulation of the isolated perfused liver by the combined infusion of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and the Ca2+ ionophore A23187 results in a transient increase of endogenous cysteinyl LT production, which is independent of extrahepatic cells. 4. The immunosuppressive drug cyclosporine causes a dose-dependent inhibition of hepatobiliary cysteinyl LT excretion, probably by interference with the sinusoidal uptake system for cysteinyl LTs.

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