Stimulation of bilirubin catabolism in jaundiced Gunn rats by an inducer of microsomal mixed-function monooxygenases

Kapitulnik, Jaime; Ostrow, J. Donald

doi:10.1073/pnas.75.2.682

Cited by 53 publications

(26 citation statements)

References 20 publications

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“…The production rates of UCB in the organ and the permeability to UCB of the blood-organ barriers (10) determine the supply of UCB. Because Gunn (jj) rats cannot conjugate bilirubin, the cellular export of UCB (15,16,18,19) and UCB oxidation (12,14,(26)(27)(28) might play a role in UCB removal from the brain of these animals.…”

Section: Discussionmentioning

confidence: 99%

Bilirubin accumulation and Cyp mRNA expression in selected brain regions of jaundiced Gunn rat pups

et al. 2012

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Section: Discussionmentioning

confidence: 99%

Bilirubin accumulation and Cyp mRNA expression in selected brain regions of jaundiced Gunn rat pups

et al. 2012

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“…Another possibility is that there are heme degradation pathways not mediated by heme oxygenase (25) and that unconjugated bilirubin may be catabolized by mixed-function monooxygenases (26). We cannot exclude an effect of SnPP to stimulate these pathways and accelerate the reduction of serum bilirubin.…”

Section: Resultsmentioning

confidence: 89%

Pharmacological and Biological Effects of Tin-Protoporphyrin on Neonatal Hyperbilirubinemic Gunn Rats

et al. 1988

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ABSTRACT. Our study was undertaken to examine the pharmacological and biological effects of tin-protoporphyrin, a competitive inhibitor of heme oxygenase, on 5-or 6-day-old homozygous Cjlj) Gunn rats with hereditary unconjugated hyperbilirubinemia. When j / j neonates were injected subcutaneously with 20 pmol of tin-protoporphyrintkg of body weight, hepatic heme oxygenase activity decreased to 30% of the initial level 2 h after administration and remained low during the next 46 h. However, the reduction of serum bilirubin was more rapid and transient, reaching the minimum value (40% of the initial level) at 1 h and increasing thereafter at a rate almost comparable to that in nontreated j/j rats. The mortality rate of j / j rats was strikingly reduced by the administration of 1 to 100 pmol of tin-protoporphyrin/kg; the most effective dose was 5 pmol/kg (8% compared with 80% in non-treated j/j rats). However, the protective effect of tin-protoporphyrin on bilirubin cerebellopathy (cerebellar hypoplasia) was less marked than expected. Possible implications of our results are discussed. (Pediatr Res 24: 209-912, 1988)

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“…Evidence for the possible involvement of CYP2A5 in BR metabolism was first reported by Berry et al (1972) that a fraction of BR is excreted as hydroxylated products in jaundiced Gunn rats, by the action of cytochrome P450 microsomes (Berryl et al, 1972;Kapitulnik and Ostrow, 1978). Later, Matteis et al (1989) established an in vitro BR disappearance activity assay using the microsomal fraction of liver homogenates after treatment with powerful inducer of CYPs,2,3,7, in vivo (Matteis et al, 1989).…”

Section: Cyp2a5 In Bilirubin Metabolismmentioning

confidence: 99%

Cytochrome P450 2A5 and bilirubin: Mechanisms of gene regulation and cytoprotection

Kim

Antenos

Squires

et al. 2013

Toxicology and Applied Pharmacology

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Murine cytochrome P450 2A5 (CYP2A5) is an interesting enzyme for its unique regulation and its involvement in liver injury caused by various well-known pathological conditions or hepatotoxins. It has been reported that CYP2A5 is upregulated following exposure to chemical hepatotoxins and during pathophysiological conditions in which the levels of most Cytochrome P450s are either unchanged or down-regulated. Recently bilirubin has been identified as the first endogenous substrate for CYP2A5 and it has been suggested that CYP2A5 plays a major role in bilirubin clearance as an alternative mechanism to BR conjugation by UGT1A1. This study investigated the mechanisms of gene regulation and cytoprotective role of CYP2A5 in response to bilirubin treatment in liver. Our results demonstrate that bilirubin induces CYP2A5 expression at the mRNA and protein levels by increasing CYP2A5 transcription via a mechanism that involves Nrf2 activation. Furthermore, our results suggest that induced CYP2A5 plays a cytoprotective role against bilirubin toxicity by directly lowering the cellular levels of bilirubin and by inhibiting caspase-3 activation.iii ACKNOWLEDGEMENTS

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Stimulation of bilirubin catabolism in jaundiced Gunn rats by an inducer of microsomal mixed-function monooxygenases

Cited by 53 publications

References 20 publications

Bilirubin accumulation and Cyp mRNA expression in selected brain regions of jaundiced Gunn rat pups

Bilirubin accumulation and Cyp mRNA expression in selected brain regions of jaundiced Gunn rat pups

Pharmacological and Biological Effects of Tin-Protoporphyrin on Neonatal Hyperbilirubinemic Gunn Rats

Cytochrome P450 2A5 and bilirubin: Mechanisms of gene regulation and cytoprotection

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