Induction of phase I, II and III drug metabolism/transport by xenobiotics

@article{Xu2005InductionOP,
  title={Induction of phase I, II and III drug metabolism/transport by xenobiotics},
  author={Changjiang Xu and Christina Yong-Tao Li and A N Kong},
  journal={Archives of Pharmacal Research},
  year={2005},
  volume={28},
  pages={249-268}
}
Drug metabolizing enzymes (DMEs) play central roles in the metabolism, elimination and detoxification of xenobiotics and drugs introduced into the human body. Most of the tissues and organs in our body are well equipped with diverse and various DMEs including phase I, phase II metabolizing enzymes and phase III transporters, which are present in abundance either at the basal unstimulated level, and/or are inducible at elevated level after exposure to xenobiotics. Recently, many important… Expand
Role of the nuclear pregnane X receptor in drug metabolism and the clinical response
The pregnane X receptor (PXR) is an orphan nuclear receptor that regulates the expression of phase I and phase II drug metabolizing enzymes and transporters involved in the absorption, distribution,Expand
Regulation of drug-metabolizing enzymes by xenobiotic receptors: PXR and CAR.
TLDR
Recent advances in the understanding of PXR and CAR as xenosensors are discussed with emphasis placed on the differences rather than similarities of these two xenobiotic receptors in ligand recognition and target gene regulation. Expand
Human and Murine Hepatic Sterol-12-a-Hydroxylase and Other Xenobiotic Metabolism mRNA Are Upregulated by
TLDR
Isoflavone-related induction of 12-a-hydroxylase (CYP8B1) was further studied in other in vitro and murine in vivo models and transfection studies suggest that isoflavones may act as a weak activating ligand for hepatocyte nuclear factor 4a, which in turn may activate the transcription of CYP8 B1. Expand
Induction of hepatic cytochrome P450 enzymes: methods, mechanisms, recommendations, and in vitro–in vivo correlations
TLDR
In this review, the authors’ current understanding of the mechanisms of enzyme induction and the in vitro methods for assessing the induction potential of new drugs will be discussed and relevant issues and considerations surrounding proper study design and the interpretation of in vitro results are discussed. Expand
Nuclear receptors in regulation of biotransformation enzymes and drug transporters in the placental barrier
TLDR
It is shown that the placenta constitute a unique metabolizing organ with significant overlap of exogenous and endogenous compounds metabolism controlled by nuclear receptors. Expand
Does hepatic steatosis affect drug metabolizing enzymes in the liver?
TLDR
Studies in animals, humans and in-vitro models suggesting altered expression of transcription factors, transporters and enzymes involved in drug metabolism in non-alcoholic fatty liver disease are summarized in the current review. Expand
Integration of hepatic drug transporters and phase II metabolizing enzymes: mechanisms of hepatic excretion of sulfate, glucuronide, and glutathione metabolites.
TLDR
This review summarizes sulfation, glucuronidation, and glutathione conjugation reactions, as well as recent progress in elucidating the hepatic transport mechanisms responsible for the excretion of these conjugates from the liver, and focuses on alterations of metabolism and transport by chemical modulators, and disease states. Expand
Coordinated Regulation of Hepatic Phase I and II Drug-Metabolizing Genes and Transporters using AhR-, CAR-, PXR-, PPARα-, and Nrf2-Null Mice
TLDR
Identification of genes encoding drug-metabolizing enzymes and transporters altered by chemical activators in a transcription factor-dependent manner and Pharmacological activation of each transcription factor leads to mRNA induction of drug metabolic and transport genes in livers of male and female wild-type mice reveal transcription factor specificity and overlap in regulating hepatic drug disposition genes by chemical activation. Expand
Chemical-induced coordinated and reciprocal changes in heme metabolism, cytochrome P450 synthesis and others in the liver of humans and rodents.
TLDR
A retrospective view of research works carried out in the department and current findings on chemical-induced changes in hepatic heme metabolism in many places are taken, together with current knowledge. Expand
Regulation of drug-metabolizing cytochrome P450 enzymes by glucocorticoids
The regulation of drug-metabolizing cytochrome P450 enzymes (CYP) is a complex process involving multiple mechanisms. Among them, transcriptional regulation through ligand-activated nuclear receptorsExpand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 190 REFERENCES
Pharmacogenomics, regulation and signaling pathways of phase I and II drug metabolizing enzymes.
TLDR
To better understand the pharmacogenomic/gene expression profile of DMEs and the underlying molecular mechanisms after exposure to xenobiotics or drugs, cDNA microarray or oligonucleotide-based DNA chip technology can be a powerful tool to analyze, simultaneously, the gene expression profiles that are induced or repressed by Xenobiotics. Expand
Role of Orphan Nuclear Receptors in the Regulation of Drug-Metabolising Enzymes
TLDR
Coadministration of drugs that are nuclear receptor agonists or antagonists can lead to severe toxicity, a loss of therapeutic efficacy or an imbalance in physiological substrates, providing a novel molecular mechanism for drug-drug interactions. Expand
Organ distribution of multidrug resistance proteins 1, 2, and 3 (Mrp1, 2, and 3) mRNA and hepatic induction of Mrp3 by constitutive androstane receptor activators in rats.
TLDR
It is concluded that rat hepatic Mrp3 is induced by CAR activators, thus enhancing the vectoral excretion of some phase II metabolites from the liver to the blood. Expand
Pathophysiological Factors Affecting CAR Gene Expression
TLDR
The hypothesis of a signal transduction where the activation of GR plays a critical function in CAR-mediated cellular response is proposed, and chemicals or pathophysiological factors that affect GR function should decrease CAR function is tested. Expand
P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR.
  • D. Waxman
  • Biology, Medicine
  • Archives of biochemistry and biophysics
  • 1999
TLDR
P450 induction by xenobiotics may in some cases lead to a perturbation of endogenous regulatory circuits with associated pathophysiological consequences, leading to the proposal that these receptors may primarily serve to modulate hepatic P450 activity in response to endogenous dietary or hormonal stimuli. Expand
Specific and overlapping functions of the nuclear hormone receptors CAR and PXR in xenobiotic response
TLDR
It is concluded that CAR has broad functions in xenobiotic responses, some are specific to CAR but others, including induction of the important drug metabolizing enzyme CYP3A, overlap with those of PXR. Expand
PXR-dependent induction of human CYP3A4 gene expression by organochlorine pesticides.
TLDR
The data suggest that chronic exposure to OCP could alter a major metabolite pathway in human liver and putatively modify the pharmacokinetics of drugs and pollutants. Expand
Humanized xenobiotic response in mice expressing nuclear receptor SXR
TLDR
It is shown that targeted disruption of the mouse PXR gene abolishes induction of CYP3A by prototypic inducers such as dexamethasone or pregnenolone-16α-carbonitrile, and that SXR/PXR genes encode the primary species-specific xeno-sensors that mediate the adaptive hepatic response, and may represent the critical biochemical mechanism of human xenoprotection. Expand
Overview of enzymes of drug metabolism
  • U. Meyer
  • Biology, Medicine
  • Journal of Pharmacokinetics and Biopharmaceutics
  • 2006
TLDR
Biotransformation means that a lipid-soluble xenobiotic or endobiotic compound is enzymatically transformed into polar, water- soluble, and excretable metabolites. Expand
The expression of CYP2B6, CYP2C9 and CYP3A4 genes: a tangle of networks of nuclear and steroid receptors.
TLDR
Different pathways controlling human CYP2B6, CYP 2C9 and CYP3A4 gene expression are reviewed, and the cross-talk between these pathways is focused on. Expand
...
1
2
3
4
5
...