Efflux of Bilirubin into Plasma following Hepatic Degradation of Exogenous Heme

Farrell, Geoffrey C.; Gollan, John L.; Schmid, Rudi

doi:10.3181/00379727-163-40805

Cited by 9 publications

(3 citation statements)

References 5 publications

(7 reference statements)

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“…The findings are in agreement with those reported in humans (6,8,13) and are consistent with the prevailing concept that transport of bilirubin across the liver plasma membrane is a bidirectional process (8,48). Experimental evidence that unconjugated bilirubin refluxes from liver to plasma has recently been obtained in studies using the radiolabeled pigment precursors 8-aminolevulinic acid (12,13,22), heme (49), and biliverdin (50). In the present animal experiments, an average of 20% of bilirubin entering the liver refluxed back into plasma, whereas in humans a value of 37% has been reported (8).…”

Section: Discussionsupporting

confidence: 82%

Bilirubin kinetics in intact rats and isolated perfused liver. Evidence for hepatic deconjugation of bilirubin glucuronides.

Gollan¹,

Hammaker²,

Ličko³

et al. 1981

J. Clin. Invest.

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Section: Discussionsupporting

confidence: 82%

Bilirubin kinetics in intact rats and isolated perfused liver. Evidence for hepatic deconjugation of bilirubin glucuronides.

Gollan¹,

Hammaker²,

Ličko³

et al. 1981

J. Clin. Invest.

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“…Acute As 3+ administration results in profound alterations of heme metabolism and elevations of the biliary excretion of bilirubin [29]. Work in rats injected with radiolabelled heme showed that the majority of the bilirubin formed from hepatic heme passes to the plasma before its biliary excretion [35]. Consistent with this, we found that acute As 3+ treatment led to increased HO-1 activity and large increases in total bilirubin serum concentrations within 24 h in the rat.…”

Section: Discussionsupporting

confidence: 83%

Acute sodium arsenite administration induces pulmonary CYP1A1 mRNA, protein and activity in the rat

Seubert

Sinal

Bend

2002

J Biochem & Molecular Tox

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Modulation of the cytochrome P450 (CYP) monooxygenase system (P450) by arsenite was investigated in male, adult Sprague-Dawley rats treated with a single dose (75 micromol/kg, sc) of sodium arsenite (As3+). Total CYP content and P450-dependent 7-pentoxyresorufin O-pentylation (PROD) and 7-ethoxyresorufin O-deethylation (EROD) activities of liver microsomes decreased maximally (33, 35, and 50% of control, respectively) 1 day after As3+ treatment. Maximum decreases of CYP content and P450 catalytic activities corresponded with maximum increases of microsomal heme oxygenase (HO) activity and with increased total plasma bilirubin concentrations. EROD activity increased maximally in lung (300%) 5 days after a single dose of As3+. Lung CYP1A1 mRNA and protein levels also increased maximally 5 days after treatment. A small but significant increase in EROD activity (65%) was observed in lung microsomes 24 h following a 1 h infusion of bilirubin (7.5 mg/kg) into rats. However, administration of bilirubin to the lung via intratracheal injection (0.25 and 2.5 mg/kg) did not increase CYP1A1 monooxygenase activity or mRNA. This study demonstrates that P450 is modulated in an isozyme (CYP1A1 vs CYP2B1/2) selective manner in rat lung after acute As3+ administration. Administration of bilirubin, a potential aryl hydrocarbon receptor (AHR) ligand, by infusion or intratracheal instillation did not upregulate pulmonary CYP1A1 at the mRNA level under our treatment conditions.

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“…Experiments in normal rats have shown that exogenously administered hematin is converted in the liver to bilirubin with an efficiency of 50 to 70%, with a substantial efflux of the bilirubin into plasma before its ultimate biliary excretion (26,27). The serum bilirubin level also increases transiently in normal human subjects and some patients with biliary obstruction after hematin injections (28).…”

Section: Discussionmentioning

confidence: 99%

Effect of hematin administration to patients with protoporphyria and liver disease

Bloomer¹,

Pierach²

1982

Hepatology

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Hepatic damage in protoporphyria appears to be caused by a toxic effect of excess protoporphyrin. Therapy which reduces the formation of excess protoporphyrin may, therefore, be helpful. We examined the effects of hematin administered i.v. to two patients with protoporphyria and decompensated cirrhosis. Neither patient had side effects from the compound or manifested signs of toxicity. The vascular disappearance of hematin in one patient was similar to that in patients with porphyria who do not have structural liver disease. In both patients, biochemical changes occurred that were compatible with a reduced rate of protoporphyrin formation. Thus, hematin administration may be useful in treating patients with protoporphyria who develop liver disease.

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Efflux of Bilirubin into Plasma following Hepatic Degradation of Exogenous Heme

Cited by 9 publications

References 5 publications

Bilirubin kinetics in intact rats and isolated perfused liver. Evidence for hepatic deconjugation of bilirubin glucuronides.

Bilirubin kinetics in intact rats and isolated perfused liver. Evidence for hepatic deconjugation of bilirubin glucuronides.

Acute sodium arsenite administration induces pulmonary CYP1A1 mRNA, protein and activity in the rat

Effect of hematin administration to patients with protoporphyria and liver disease

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