Investigation of nonalcoholic fatty liver disease‐induced drug metabolism by comparative global toxicoproteomics

  title={Investigation of nonalcoholic fatty liver disease‐induced drug metabolism by comparative global toxicoproteomics},
  author={Ann-Yae Na and J. Jo and O. K. Kwon and Riya Shrestha and P. Cho and Kyu Min Kim and S. Ki and T. Lee and T. Jeon and T. Jeong and Sangkyu Lee},
  journal={Toxicology and Applied Pharmacology},
&NA; Non‐alcoholic fatty liver disease (NAFLD) includes conditions such as steatosis, non‐alcoholic steatohepatitis, and ultimately hepatocellular carcinoma. Although the pathology of NAFLD is well‐established, NAFLD‐induced drug metabolism mediated by cytochrome P450 (CYP) in the liver has remained largely unexplored. Therefore, we investigated NAFLD‐induced drug metabolism mediated by CYP by quantitative toxicoproteomics analysis. After administration of a methionine‐choline deficient (MCD… Expand
Elucidation of CYP Inducibility and Inflammatory Response via Cytokine Release in Non- Alcoholic Fatty Liver Disease
Non-alcoholic fatty liver disease (NAFLD) is an emerging global health issue that has recently reached 20% in global prevalence and is projected to be the main cause of liver morbidity in the nextExpand
Cyp2b-null male mice are susceptible to diet-induced obesity and perturbations in lipid homeostasis.
Overall the data indicates that the repression or inhibition of CYP2B may exacerbate metabolic disorders and cause obesity by perturbing fatty acid metabolism, especially in males. Expand
Studying the effects of sea cucumber ovum powder on nonalcoholic fatty liver disease by proteomics techniques in a rat model.
The results in this study provide an overview of the SCO-induced changes in the liver proteome of NAFLD, which may help to understand the molecular mechanism behind the effects of SCO on the alleviation ofNAFLD. Expand
Sexual Dimorphism in Drug Metabolism and Pharmacokinetics.
Sex and gender-based differences in the metabolism of drugs exist at various levels and it may be due to the genomic and non-genomic action of sex hormones. Expand


Drug metabolism alterations in nonalcoholic fatty liver disease
The current review is intended to present the results from both animal models and human patients, summarizing the observed alterations in the expression and activity of the phase I and II drug-metabolizing enzymes. Expand
Effects of Nonalcoholic Fatty Liver Disease on Hepatic CYP2B1 and in Vivo Bupropion Disposition in Rats Fed a High-Fat or Methionine/Choline-Deficient Diet.
This study investigated the hepatic cytochrome P450 (CYP) 2B1-modulating effect of a specific NAFLD state in dietary rat models and found that the enzyme-kinetic and pharmacokinetic parameters for CYP2 B1-mediated bupropion metabolism were considerably reduced in MCD diet-fed rats; however, they were also similar between the HF diet- fed and control rats. Expand
Proteomic Analysis of Mice Fed Methionine and Choline Deficient Diet Reveals Marker Proteins Associated with Steatohepatitis
Findings suggest that curcumin may have a protective role against MCD fed-induced oxidative stress andPeroxiredoxin (Prx) is the most interesting among the modulated proteins identified and is likely to participate in cellular defense against the development of hepatitis. Expand
Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats.
Data suggest that different stages of NAFLD result in altered hepatic uptake transporter expression that can lead to a functional impairment of xenobiotic uptake from the blood and may alter the plasma retention time of clinically relevant drugs that are reliant on these transporters and may increase the potential drug toxicity. Expand
In vivo cytochrome P450 activity alterations in diabetic nonalcoholic steatohepatitis mice
The data suggest that the diabetic NASH model only partially recapitulates the human ex vivo CYP alteration pattern, and in vivo determination of the effects of NASH on CYP activity should be conducted in human, and more appropriate models are required for future drug metabolism studies in NASH. Expand
Specific Contribution of Methionine and Choline in Nutritional Nonalcoholic Steatohepatitis
The depletion of SAM and GSH in mitochondria is an early event in the MCD model of NASH, which is determined by the lack of methionine, and therapy using permeable GSH prodrugs may be of relevance in NASH. Expand
Animal models of nonalcoholic fatty liver disease
This Review discusses the prevalent dietary and inflammation-based genetic animal models described in recent years that have been undertaken using animals to model human steatosis and NAFLD to NASH disease progression. Expand
Role of adipose triglyceride lipase (PNPLA2) in protection from hepatic inflammation in mouse models of steatohepatitis and endotoxemia
These findings unravel a novel protective role of ATGL against hepatic inflammation which could have important implications for metabolic and inflammatory liver diseases. Expand
Hepatic Cytochrome P450 Enzyme Alterations in Humans with Progressive Stages of Nonalcoholic Fatty Liver Disease The online version of this article (available at contains supplemental material.
It is suggested that significant and novel changes occur in hepatic P450 activity during progressive stages of nonalcoholic fatty liver disease and elevated CYP2C9 activity during NAFLD progression correlated with elevated hypoxia-induced factor 1α expression in the later stages ofNAFLD. Expand
Hepatic Cytochrome P 450 Enzyme Alterations in Humans with Progressive Stages of Nonalcoholic Fatty Liver Disease
Members of the cytochrome P450 (P450) enzyme families CYP1, CYP2, and CYP3 are responsible for the metabolism of approximately 75% of all clinically relevant drugs. With the increased prevalence ofExpand