Metabolism of bisphenol a in primary cultured hepatocytes from mice, rats, and humans.

@article{Pritchett2002MetabolismOB,
  title={Metabolism of bisphenol a in primary cultured hepatocytes from mice, rats, and humans.},
  author={J J Pritchett and Robert K. Kuester and I. Glenn Sipes},
  journal={Drug metabolism and disposition: the biological fate of chemicals},
  year={2002},
  volume={30 11},
  pages={
          1180-5
        }
}
Studies have shown that in the rat, bisphenol A (BPA) is metabolized and eliminated primarily as a monoglucuronide, a metabolite without estrogenic activity. The purpose of this study was to determine the extent of monoglucuronide formation in monolayers of hepatocytes from rats, mice, and humans. Noncytotoxic concentrations of BPA (10, 20, and 35 microM; 1.0 microCi), as assessed by lactate dehydrogenase leakage, were incubated with isolated hepatocytes for 0-6 h. Media were collected and… 
View on PubMed
dmd.aspetjournals.org
126 Citations
Highly Influential Citations
10
Background Citations
64
Methods Citations
7
Results Citations
5

Figures and Tables from this paper

126 Citations

Citation Type

Citation Type

Bisphenol A glucuronide/sulfate diconjugate in perfused liver of rats
TLDR
The results suggest that BPA is conjugated primarily to mono-glucuronide in rat liver; and that in males, diconjugate production occurs under conditions of high-dose exposure to BPA.
Species difference of metabolic clearance of bisphenol A using cryopreserved hepatocytes from rats, monkeys and humans.
Bis(hydroxyphenyl)methane—bisphenol F—metabolism by the HepG2 human hepatoma cell line and cryopreserved human hepatocytes
TLDR
The metabolism of BPF in both HepG2 cells and human hepatocytes suggests the existence of a detoxification pathway, and these two cell models differ in metabolic capacity.
In Vitro Glucuronidation of 2,2-Bis(bromomethyl)-1,3-propanediol by Microsomes and Hepatocytes from Rats and Humans
TLDR
The poor glucuronidation capacity of humans for BMP suggests that the pharmacokinetic profile of BMP in humans will be dramatically different from that of rodents.
Stereoselective toxicity and metabolism of lactofen in primary hepatocytes from rat.
TLDR
For the cytotoxicity research, the calculated EC50 values indicated that when being applied individually, the parent compound was less toxic than its metabolites, while the combination with metabolites enhanced its cytotoxic effects.
METABOLISM OF N-HYDROXYGUANIDINES (N-HYDROXYDEBRISOQUINE) IN HUMAN AND PORCINE HEPATOCYTES: REDUCTION AND FORMATION OF GLUCURONIDES
TLDR
The objective of the present work was to compare the N-oxidative and N-reductive metabolism of this compound using a monolayer culture system with previously described microsomal studies and to investigate the phase 2 metabolism, in particular, the glucuronidation of this class of compounds.
Direct effects of Bisphenol A on lipid homeostasis in rat hepatoma cells.
BISPHENOL A GLUCURONIDATION AND EXCRETION IN LIVER OF PREGNANT AND NONPREGNANT FEMALE RATS
TLDR
Results suggest that bisphenol A elimination by hepatic glucuronidation is slightly less in pregnancy than in non-pregnancy and that in pregnancy, more bispenol A glucuronide is eliminated to the vein because of reduced MRP2 expression.
Biotransformation and cytotoxicity of a brominated flame retardant, tetrabromobisphenol A, and its analogues in rat hepatocytes
TLDR
Mitochondria are target organelles for TBBPA, which elicits cytotoxicity through mitochondrial dysfunction related to oxidative phosphorylation at an early stage and subsequently lipid peroxidation at a later stage, and the toxicity of T BBPA and TCBPA is greater than that of BPA, suggesting the participation of halogen atoms such as bromine and chlorine in the toxicity.
Differences between Human and Rat Intestinal and Hepatic Bisphenol A Glucuronidation and the Influence of Alamethicin on In Vitro Kinetic Measurements
TLDR
The species and gender metabolic differences the authors observed between rat and human liver and intestine provide key information for delineating BPA pharmacokinetics needed for human health risk assessment.
...
...

References

SHOWING 1-10 OF 24 REFERENCES
Metabolism and cytotoxicity of bisphenol A and other bisphenols in isolated rat hepatocytes
TLDR
The results indicate that the onset of cytotoxicity caused by BPA may depend on the intracellular energy status and that mitochondria are important targets of the compound.
Comparison of the modulatory effects of human and rat liver microsomal metabolism on the estrogenicity of bisphenol A: implications for extrapolation to humans.
TLDR
Because human liver microsomes did not glucuronidate BPA as extensively as the rat livermicrosomes, estrogen target tissues in humans may be subject to greater exposure to BPA than the tissues of the immature female rats used for assessing estrogenicity of xenobiotics.
Bisphenol a glucuronide, a major metabolite in rat bile after liver perfusion.
TLDR
Most bisphenol A absorbed by the intestine is probably glucuronidated exclusively in the liver and the conjugate is excreted mainly into the bile.
Prediction of furan pharmacokinetics from hepatocyte studies: comparison of bioactivation and hepatic dosimetry in rats, mice, and humans.
TLDR
One important consequence of blood flow limitation of furan bioactivation is that the amount of toxic metabolite formed in the liver will be unaffected by increases in Vmax due to the induction of cytochrome P450 2E1.
Studies on trans-cinnamaldehyde. 1. The influence of dose size and sex on its disposition in the rat and mouse.
  • M. M. Peters, J. Caldwell
  • Biology, Chemistry
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 1994
The relative bioavailability and metabolism of bisphenol A in rats is dependent upon the route of administration.
TLDR
A route dependency of BPA bioavailability in rats is demonstrated, with oral administration resulting in the lowest bioavailability, and explanation for the apparent route differences in estrogenic potency observed for BPA is offered.
Conjugation of desmethylnaproxen in the rat--a novel acyl glucuronide-sulfate diconjugate as a major biliary metabolite.
TLDR
No evidence for a diglucuronide metabolite of DMN was found in either bile or urine of the DMN-dosed rats, and tentative identification of the two unknown peaks as the phenolic glucuronide ofDMN and a novel acyl glucuronides-sulfate diconjugate of DMn was confirmed.
Toxicokinetics of bisphenol A in female DA/Han rats after a single i.v. and oral administration
TLDR
The toxicokinetic properties of BPA in DA/Han rats are in agreement with the hypothesis of a rapid first-pass elimination by the liver and efficient metabolic clearance of low oral doses, and only excessive doses may lead to bioaccumulation if detoxification pathways are saturated.
Glucuronidation of the environmental oestrogen bisphenol A by an isoform of UDP-glucuronosyltransferase, UGT2B1, in the rat liver.
TLDR
Results indicate that bisphenol A, in male rat liver, is glucuronidated by UGT2B1, an isoform of UGT, which glucuronidates some endogenous androgens.
In Vitro and in Vivo Interactions of Bisphenol A and Its Metabolite, Bisphenol A Glucuronide, with Estrogen Receptors α and β
TLDR
Results demonstrate that BPA competes more effectively for binding to ERbeta, but induces ERalpha- and ERbeta-mediated gene expression with comparable efficacy, while BPA-G did not exhibit any in vitro estrogenic activity.
...
...