Increase in a specific cytochrome <i>P</i>-450 isoenzyme in the liver of congenitally jaundiced Gunn rats

Kapitulnik, Jaime; Hardwick, James P.; Ostrow, J. Donald; Webster, Cecile; Park, Sangshin; Gelboin, Harry V.

doi:10.1042/bj2420297

Cited by 24 publications

(10 citation statements)

References 25 publications

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“…This difference suggests that as UCB accumulates, an increasingly smaller fraction of the UCB load resides extravascularly. This phenomenon may result from increased activity of facilitated and active transport mechanisms for extravascular efflux of UCB (28 ), nonconjugating pathways for UCB catabolism (31,32 ), and increasing saturation of non-CNS extravascular UCB reservoirs such as fatty tissue (Ͻ1% of the extravascular UCB resides in the CNS in animal models) (33 ). Fig.…”

Section: Abe B T and B F : The Rationale For Measuring B F In Jaunmentioning

confidence: 99%

Unbound (Free) Bilirubin: Improving the Paradigm for Evaluating Neonatal Jaundice

et al. 2009

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Background: The serum or plasma total bilirubin concentration (BT) has long been the standard clinical laboratory test for evaluating neonatal jaundice, despite studies showing that BT correlates poorly with acute bilirubin encephalopathy (ABE) and its sequelae including death, classical kernicterus, or bilirubin-induced neurological dysfunction (BIND). The poor correlation between BT and ABE is commonly attributed to the confounding effects of comorbidities such as hemolytic diseases, prematurity, asphyxia, or infection. Mounting evidence suggests, however, that BT inherently performs poorly because it is the plasma non–protein-bound (unbound or free) bilirubin concentration (Bf), rather than BT, that is more closely associated with central nervous system bilirubin concentrations and therefore ABE and its sequelae. Content: This article reviews (a) the complex relationship between serum or plasma bilirubin measurements and ABE, (b) the history underlying the limited use of Bf in the clinical setting, (c) the peroxidase method for measuring Bf and technical and other issues involved in adapting the measurement to routine clinical use, (d) clinical experience using Bf in the management of newborn jaundice, and (e) the value of Bf measurements in research investigating bilirubin pathochemistry. Summary: Increasing evidence from clinical studies, clinical experience, and basic research investigating bilirubin neurotoxicity supports efforts to incorporate Bf expeditiously into the routine evaluation of newborn jaundice. .

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Section: Abe B T and B F : The Rationale For Measuring B F In Jaunmentioning

confidence: 99%

Unbound (Free) Bilirubin: Improving the Paradigm for Evaluating Neonatal Jaundice

et al. 2009

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“…UCB induced cytochrome P4501A1 in jaundiced Gunn rats (Kapitulnik et al, 1987;Kapitulnik and Gonzalez, 1993), thus enabling the elimination of UCB in these glucuronidation-deficient animals (Kapitulnik and Ostrow, 1978). Relatively low concentrations of UCB (10 M) activated the AhR in cultured hepatoma cells (Sinal and Bend, 1997;Phelan et al, 1998).…”

Section: Cytoprotective Effects Of Bilirubinmentioning

confidence: 99%

Bilirubin: An Endogenous Product of Heme Degradation with Both Cytotoxic and Cytoprotective Properties: Fig. 1

Kapitulnik¹

2004

Mol Pharmacol

219

180

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“…An additional facet of the protective role of UCB is manifested by its capacity to induce CYP1A1 (cytochrome P450 1A1) in jaundiced Gunn rats [78,79], thus enabling the elimination of UCB in these glucuronidation-deficient animals [80]. Low concentrations of UCB (10-50 μmol/l) induced CYP1A1 expression via AhR (aryl hydrocarbon receptor)-mediated transcriptional gene activation [81,82].…”

Section: Cytoprotective Properties Of Bilirubin Resulting From Its Anmentioning

confidence: 99%

Complement activation and disease: protective effects of hyperbilirubinaemia

et al. 2009

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Complement, an important effector mechanism of the immune system, is an enzymatic cascade of approx. 30 serum proteins leading to the amplification of a specific humoral response. It can be activated through the classical or alternative pathways, or through the mannose-binding lectin pathway. The activation of the classical pathway is initiated by the binding of the C1 component to antigen-bound antibodies, known as immunocomplexes. C1 is a complex of one molecule of C1q, two molecules of C1r and two molecules of C1s. C1q contains three copies of a Y-shaped fundamental unit with globular heads included in its structure, which play a major role in the interaction with the Fc portion of immunoglobulins. Deficient or exacerbated activation of the complement system leads to diseases of variable severity, and pharmacological inhibition of the complement system is considered as a therapeutic strategy to ameliorate the inflammatory effects of exacerbated complement activation. Bilirubin is a product of haem degradation by the concerted action of haem oxygenase, which converts haem into biliverdin, and biliverdin reductase, which reduces biliverdin to UCB (unconjugated bilirubin). UCB exerts both cytoprotective and cytotoxic effects in a variety of tissues and cells, acting either as an antioxidant at low concentrations or as an oxidant at high concentrations. In the present review, we describe in detail the anti-complement properties of bilirubin, occurring at levels above the UCB concentrations found in normal human serum, as a beneficial effect of potential clinical relevance. We provide evidence that UCB interferes with the interaction between C1q and immunoglobulins, thus inhibiting the initial step in the activation of complement through the classical pathway. A molecular model is proposed for the interaction between UCB and C1q.

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Increase in a specific cytochrome P-450 isoenzyme in the liver of congenitally jaundiced Gunn rats

Cited by 24 publications

References 25 publications

Unbound (Free) Bilirubin: Improving the Paradigm for Evaluating Neonatal Jaundice

Unbound (Free) Bilirubin: Improving the Paradigm for Evaluating Neonatal Jaundice

Bilirubin: An Endogenous Product of Heme Degradation with Both Cytotoxic and Cytoprotective Properties: Fig. 1

Complement activation and disease: protective effects of hyperbilirubinaemia

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