1,243 results match your criteria induction cyp2e1


Cytochrome P450 2E1 (CYP2E1) positively regulates lipid catabolism and induces browning in 3T3-L1 white adipocytes.

Life Sci 2021 Aug 24;278:119648. Epub 2021 May 24.

Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk 38453, Republic of Korea. Electronic address:

Aims: Browning induction (beiging) of white adipocytes is an emerging prospective strategy to defeat obesity and its related metabolic disorders. Cytochrome P450 2E1 (CYP2E1), a membrane protein which belongs to the cytochrome P450 superfamily, reportedly functions in the xenobiotic metabolism in the body, especially ethanol metabolism. Although previous studies have reported the effect of CYP2E1 on obesity in animal models, the data remains controversial. Read More

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Drug-induced-acute liver failure: A critical appraisal of the thioacetamide model for the study of hepatic encephalopathy.

Toxicol Rep 2021 30;8:962-970. Epub 2021 Apr 30.

Department of Hepatology CA-3163, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark.

Hepatic encephalopathy (HE) following acute and chronic liver failure is defined as a complex of neuropsychiatric abnormalities, such as discrete personal changes, sleep disorder, forgetfulness, confusion, and decreasing the level of consciousness to coma. The use and design of suitable animal models that represent clinical features and pathological changes of HE are valuable to map the molecular mechanisms that result in HE. Among different types of animal models, thioacetamide (TAA) has been used extensively for the induction of acute liver injury and HE. Read More

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Spatial Reconstruction of the Early Hepatic Transcriptomic Landscape after an Acetaminophen Overdose using Single-cell RNA Sequencing.

Toxicol Sci 2021 May 12. Epub 2021 May 12.

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA.

An acetaminophen (APAP) overdose is the most common cause of acute liver failure in the United States. A hallmark characteristic of APAP hepatotoxicity is centrilobular necrosis. General, innate mechanisms such as lower amounts of GSH and higher Cyp2e1 expression in pericentral (PC) hepatocytes are known to contribute to the differences in susceptibility to cell injury between periportal (PP) hepatocytes and PC hepatocytes. Read More

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PPARα agonist WY-14,643 enhances ethanol metabolism in mice: Role of catalase.

Free Radic Biol Med 2021 Jun 20;169:283-293. Epub 2021 Apr 20.

Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1700 3rd Avenue, Huntington, WV, 25755, USA; Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, 25755, USA. Electronic address:

Peroxisome proliferator-activated receptor α (PPARα), a fatty acid oxidation regulator, inhibits alcohol-induced fatty liver (AFL). PPARα agonist WY-14,643 ameliorates AFL. Nicotine enhances AFL. Read More

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Inhibition and Induction by Poziotinib of Different Rat Cytochrome P450 Enzymes and in an Cocktail Method.

Front Pharmacol 2020 5;11:593518. Epub 2021 Jan 5.

The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, China.

Poziotinib is an orally active, irreversible, pan-HER tyrosine kinase inhibitor used to treat non-small cell lung cancer, breast cancer, and gastric cancer. Poziotinib is currently under clinical investigation, and understanding its drug-drug interactions is extremely important for its future development and clinical application. The cocktail method is most suitable for evaluating the activity of cytochrome P450 enzymes (CYPs). Read More

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January 2021

5-O-Demethylnobiletin Alleviates CCl-Induced Acute Liver Injury by Equilibrating ROS-Mediated Apoptosis and Autophagy Induction.

Int J Mol Sci 2021 Jan 22;22(3). Epub 2021 Jan 22.

Advanced Bio Convergence Center (ABCC), Pohang Technopark Foundation, Pohang 37668, Korea.

Polymethoxyflavanoids (PMFs) have exhibited a vast array of therapeutic biological properties. 5-O-Demethylnobiletin (5-DN) is one such PMF having anti-inflammatory activity, yet its role in hepatoprotection has not been studied before. Results from in vitro study revealed that 5-DN did not exert a high level of cytotoxicity on HepG2 cells at 40 μM, and it was able to rescue HepG2 cell death induced by carbon tetrachloride (CCl). Read More

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January 2021

Hepatoprotection by Ginsenoside Rg1 in alcoholic liver disease.

Int Immunopharmacol 2021 Mar 4;92:107327. Epub 2021 Jan 4.

Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address:

Alcoholic hepatitis (AH) has caused serious mortality to the world's population. Despite tremendous efforts to reduce disease burden, effective treatments for this disease are still lacking. Ginsenoside Rg1 (G-Rg1) has been reported to be hepatoprotective in several liver injury models. Read More

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Toxicological responses of BEAS-2B cells to repeated exposures to benzene, toluene, m-xylene, and mesitylene using air-liquid interface method.

J Appl Toxicol 2020 Dec 2. Epub 2020 Dec 2.

Unité de Chimie Environnementale et Interactions sur le Vivant, SFR Condorcet FR CNRS 3417, Université du Littoral Côte d'Opale, Dunkirk, France.

In order to reduce exposure to toxic chemicals, the European REACH regulation (1907/2006) recommends substituting toxic molecules with compounds that are less harmful to human health and the environment. Toluene is one of the most frequently used solvents in industries despite its toxicity. The objective of this study is to better understand and compare the toxicity of toluene and its homologues in a bronchial cell model. Read More

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December 2020

Genotoxicity and subchronic toxicity studies of supercritical carbon dioxide and acetone extracts of rosemary.

Regul Toxicol Pharmacol 2021 Feb 19;119:104826. Epub 2020 Nov 19.

Intertek Health Sciences Inc, Room 1036, Building A8, Cody Technology Park, Ively Road, Farnborough, Hampshire, UK.

Toxicology studies conducted with oil-soluble rosemary extracts to support authorization as a food additive (antioxidant) in the EU include an Ames test using a supercritical carbon dioxide extract (D74), a full 90-day study using D74 and an acetone extract (F62), and an investigative 90-day study with a 28-day recovery period (using D74 only). D74 was non-mutagenic in the Ames test. In the full 90-day study, where rats (20/sex/group) were either provided control diet or diets containing D74 (300, 600, or 2400 mg/kg) or F62 (3800 mg/kg), liver enlargement and hepatocellular hypertrophy were observed. Read More

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February 2021

Detection of urethane-induced genotoxicity in vitro using metabolically competent human 2D and 3D spheroid culture models.

Mutagenesis 2020 Nov 21. Epub 2020 Nov 21.

In Vitro Toxicology Group, Institute of Life Science 1, Singleton Campus, Swansea University Medical School, Swansea University, Swansea, UK.

In vitro genotoxicity studies are a quick and high throughput approach to assess the genotoxic potential of chemicals; however, the reliability of these tests and their relevance to in vivo effects depends on the choice of representative cell line and optimisation of assay conditions. For chemicals like urethane that require specific metabolic activation to cause genotoxicity, it is important that in vitro tests are conducted using cell lines exhibiting the activity and induction of CYP450 enzymes, including CYP2E1 enzyme that is important in the metabolism of urethane, at a concentration representing actual or perceived chemical exposure. We compared 2D MCL-5 cells and HepG2 cells with 3D HepG2 hanging drop spheroids to determine the genotoxicity of urethane using the micronucleus assay. Read More

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November 2020

Indoxylsulfate, a Metabolite of the Microbiome, Has Cytostatic Effects in Breast Cancer via Activation of AHR and PXR Receptors and Induction of Oxidative Stress.

Cancers (Basel) 2020 Oct 10;12(10). Epub 2020 Oct 10.

Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1., 4032 Debrecen, Hungary.

Changes to bacterial metabolite-elicited signaling, in oncobiosis associated with breast cancer, plays a role in facilitating the progression of the disease. We show that indoxyl-sulfate (IS), a tryptophan metabolite, has cytostatic properties in models of breast cancer. IS supplementation, in concentrations corresponding to the human serum reference range, suppressed tumor infiltration to the surrounding tissues and metastasis formation in a murine model of breast cancer. Read More

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October 2020

inhibition and induction of human liver cytochrome P450 enzymes by a novel anti-fibrotic drug fluorofenidone.

Xenobiotica 2021 Jul 18;51(7):745-751. Epub 2021 May 18.

School of Xiangya Pharmaceutical Sciences, Central South University, Changsha, China.

Fluorofenidone (AKF-PD) is an analog of pirfenidone and shows stronger antifibrotic effect and lower toxicity compared to pirfenidone in preclinical studies. However, the inhibitory and inducible effects of AKF-PD on human CYP450s are unclear. The aim of this study was to evaluate the ability of AKF-PD to inhibit and induce CYP450s . Read More

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High-fat diet induces fibrosis in mice lacking CYP2A5 and PPARα: a new model for steatohepatitis-associated fibrosis.

Am J Physiol Gastrointest Liver Physiol 2020 11 2;319(5):G626-G635. Epub 2020 Sep 2.

Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia.

Obesity is linked to nonalcoholic steatohepatitis. Peroxisome proliferator-activated receptor-α (PPARα) regulates lipid metabolism. Cytochrome -450 2A5 (CYP2A5) is a potential antioxidant and CYP2A5 induction by ethanol is CYP2E1 dependent. Read More

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November 2020

Transcript and protein marker patterns for the identification of steatotic compounds in human HepaRG cells.

Food Chem Toxicol 2020 Nov 15;145:111690. Epub 2020 Aug 15.

German Federal Institute for Risk Assessment, Dept. Food Safety, Berlin, Germany. Electronic address:

Non-alcoholic fatty liver disease is a major health concern especially in Western countries. Animal studies suggest that certain chemicals may contribute to hepatocellular triglyceride accumulation, among them a number of hepatotoxic pesticidal active compounds. In order to improve the identification of potential liver steatosis inducers in vitro in a human cell culture system, HepaRG cells were treated with a selection of 30 steatotic or non-steatotic pesticides. Read More

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November 2020

Expression of type I collagen in response to Isoniazid exposure is indirect and is facilitated by collateral induction of cytochrome P450 2E1: An in-vitro study.

PLoS One 2020 31;15(7):e0236992. Epub 2020 Jul 31.

Centre for Liver Research, School of Digestive & Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India.

We wanted to investigate whether Isoniazid (INH) can directly stimulate activation of hepatic stellate cells (HSCs) and enhance production of collagen. Treatment of human hepatic stellate cell line LX2 with or without 5μM INH for 24 to 72 hours was performed to look into content of cytochrome P450 2E1 (CYP2E1), activity of NADPH oxidase (NOX) and intracellular oxidative stress. Protein level as well as mRNA expression of alpha smooth muscle actin (α-SMA) and collagen1A1 (COL1A1) were assessed by western blot and real time PCR. Read More

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September 2020

Cytochrome P450 2E1 should not be neglected for acetaminophen-induced liver injury in metabolic diseases with altered insulin levels or glucose homeostasis.

Clin Res Hepatol Gastroenterol 2021 Jan 19;45(1):101470. Epub 2020 Jun 19.

INSERM, Université de Rennes, INRAE, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, 35000 Rennes, France. Electronic address:

Acetaminophen (APAP) hepatotoxicity is mediated by N-acetyl-p-benzoquinone imine (NAPQI), a highly toxic metabolite generated by cytochrome P450 2E1 (CYP2E1). Thus, pathological conditions increasing CYP2E1 activity can favour APAP-induced liver injury, which is characterized by massive hepatocellular necrosis and secondary sterile inflammation. In a recent work, Wang et al. Read More

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January 2021

Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms.

J Vis Exp 2020 05 29(159). Epub 2020 May 29.

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University; Department of Pediatrics and Pathology, Johns Hopkins University;

Drug-induced autoimmune hepatitis (DIH) is the most common hepatic drug-induced hypersensitization process observed in approximately 9 to 12% of patients with autoimmune hepatitis. The overwhelming majority of patients with DIH are women. The underlying mechanisms of these sex differences in prevalence are unclear because of the paucity of animal models that mimic human disease. Read More

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Analysis of Biomarkers of DNA Damage and Mutagenicity in Mice Exposed to Acrylonitrile.

Chem Res Toxicol 2020 07 28;33(7):1623-1632. Epub 2020 Jun 28.

Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario K1A 0K9, Canada.

Acrylonitrile (ACN), which is a widely used industrial chemical, induces cancers in the mouse via unresolved mechanisms. For this report, complementary and previously described methods were used to assess in vivo genotoxicity and/or mutagenicity of ACN in several mouse models, including (i) female mice devoid of cytochrome P450 2E1 (CYP2E1), which yields the epoxide intermediate cyanoethylene oxide (CEO), (ii) male transgenic mice, and (iii) female (wild-type) B6C3F1 mice. Exposures of wild-type mice and CYP2E1-null mice to ACN at 0, 2. Read More

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β-Naphthoflavone and Ethanol Reverse Mitochondrial Dysfunction in A Parkinsonian Model of Neurodegeneration.

Int J Mol Sci 2020 May 31;21(11). Epub 2020 May 31.

Dipartimento di Scienze della Vita, Università di Siena, 53100 Siena, Italy.

The 1-methyl-4-phenylpyridinium (MPP) is a parkinsonian-inducing toxin that promotes neurodegeneration of dopaminergic cells by directly targeting complex I of mitochondria. Recently, it was reported that some Cytochrome P450 (CYP) isoforms, such as CYP 2D6 or 2E1, may be involved in the development of this neurodegenerative disease. In order to study a possible role for CYP induction in neurorepair, we designed an in vitro model where undifferentiated neuroblastoma SH-SY5Y cells were treated with the CYP inducers β-naphthoflavone (βNF) and ethanol (EtOH) before and during exposure to the parkinsonian neurotoxin, MPP. Read More

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Cross talk between alcohol-induced oxidative stress and HCV replication.

Arch Microbiol 2020 Sep 24;202(7):1889-1898. Epub 2020 May 24.

Department of Virology, Pasteur Institute of Iran, No. 69, Pasteur Ave, 1316943551, Tehran, Iran.

Alcohol consumption exacerbates the pathogenesis of hepatitis C virus (HCV) infection and aggravates disease consequences in alcohol-abusing patients. Although the exact reasons by which alcohol consumption affects several cellular pathways in liver cells are not clear, they might be partially attributed to the ability of alcohol to further suppress the innate immunity, modulation of autophagy and also its relationship with reactive oxygen species (ROS) generation. To evaluate these issues, Huh7 cells harboring HCV replicon and Cytochrome p450 (CYP2E1) plasmid were exposed to ethanol and mRNA expression of Beclin-1, interferon-stimulated gene15 (ISG15) genes and HCV NS5B for two different times were relatively quantitated. Read More

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September 2020

Apoptotic and cell cycle response to homoharringtonine and harringtonine in wild and mutant p53 hepatocarcinoma cells.

Hum Exp Toxicol 2020 Oct 20;39(10):1405-1416. Epub 2020 May 20.

Laboratório de Genética Toxicológica, Departamento de Biologia Geral, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.

This study aimed to evaluate the modes of action of harringtonine (HT) and homoharringtonine (HHT) alkaloids in cell with wild (HepG2/C3A) and mutant p53 (HuH-7.5). We performed assays for cytotoxicity, genotoxicity, induction of apoptosis, cell cycle phase, and membrane integrity. Read More

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October 2020

Human CYP2E1-dependent mutagenicity of benzene and its hydroxylated metabolites in V79-derived cells: Suppression and enhancement by ethanol pretreatment.

Environ Mol Mutagen 2020 07 25;61(6):622-634. Epub 2020 Apr 25.

Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou, China.

Benzene is a human carcinogen that requires metabolic activation. We previously observed that benzene and its hydroxylated metabolites induce micronuclei in mammalian cells expressing human CYP2E1. This study was initially aimed to study another endpoint, the induction of gene mutations by those compounds in the same cell models. Read More

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Non-oxidative ethanol metabolism in human hepatic cells in vitro: Involvement of uridine diphospho-glucuronosyltransferase 1A9 in ethylglucuronide production.

Toxicol In Vitro 2020 Aug 10;66:104842. Epub 2020 Apr 10.

Univ Rennes, INSERM, INRAE, Institut NuMeCan (Nutrition, Metabolisms and Cancer) UMR-A 1341, UMR-S 1241, F-35000 Rennes, France; CHU Rennes, Laboratoire de toxicologie médico-légale, F-35000 Rennes, France. Electronic address:

Ethanol is the most frequently psychoactive substance used in the world, leading to major public health problems with several millions of deaths attributed to alcohol consumption each year. Metabolism of ethanol occurs mainly in the liver via the predominant oxidative metabolism pathway involving phase I enzymes including alcohol dehydrogenases (ADH), cytochrome P450 (CYP) 2E1 and catalase. In a lesser extent, an alternative non-oxidative pathway also contributes to the metabolism of ethanol, which involves the uridine diphospho-glucuronosyltransferase (UGT) and sulfotransferase (SULT) phase II enzymes. Read More

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Role of Alcohol Drinking in Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis.

Int J Mol Sci 2020 Mar 27;21(7). Epub 2020 Mar 27.

Departments of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), increase as the population ages around the world. Environmental factors also play an important role in most cases. Alcohol consumption exists extensively and it acts as one of the environmental factors that promotes these neurodegenerative diseases. Read More

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Induction of SIRT1 by melatonin improves alcohol-mediated oxidative liver injury by disrupting the CRBN-YY1-CYP2E1 signaling pathway.

J Pineal Res 2020 Apr 28;68(3):e12638. Epub 2020 Feb 28.

School of Applied Biosciences, Kyungpook National University, Daegu, Korea.

Alcoholic liver disease is the most prevalent chronic liver disease. Melatonin is known to control many vital processes. Here, we explored a novel molecular mechanism by which melatonin-induced SIRT1 signaling protects against alcohol-mediated oxidative stress and liver injury. Read More

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Irbesartan mitigates acute liver injury, oxidative stress, and apoptosis induced by acetaminophen in mice.

J Biochem Mol Toxicol 2020 Dec 22;34(12):e22447. Epub 2020 Jan 22.

Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.

Hepatotoxicity induced by acetaminophen (APAP)-overdose is a major concern in clinical practice. In the present work, the detoxifying effect of irbesartan (Irb) on the APAP-induced acute liver injury was evaluated in mice. Induction of acute liver injury in mice was established by a single intraperitoneal (IP) injection of APAP (0. Read More

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December 2020

2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside alleviated the acute hepatotoxicity and DNA damage in diethylnitrosamine-contaminated mice.

Life Sci 2020 Feb 9;243:117274. Epub 2020 Jan 9.

Department of Toxicology, Shanxi Provincial Key Lab of Free radical biology and medicine, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address:

Aims: 2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside (TSG) is the key bioactive ingredient extracted from Polygonum multiflorum Thumb. Pharmacological studies suggest that it exerts numerous biological effects, including anti-oxidant, anti-aging, and anti-inflammation. This study aimed at investigating the effect of TSG on diethylnitrosamine (DEN)-induced acute hepatotoxicity and DNA damage. Read More

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February 2020

Kinetic study of the expression of genes related to hepatic steatosis, glucose and lipid metabolism, and cellular stress during overfeeding in mule ducks.

Am J Physiol Regul Integr Comp Physiol 2020 02 8;318(2):R453-R467. Epub 2020 Jan 8.

Institut National de la Recherche Agronomique, Univ Pau & Pays Adour, Energy and Environment Solutions initiative, Nutrition, Métabolisme, Aquaculture, Saint-Pée-sur-Nivelle, France.

Induced by overfeeding, hepatic steatosis is a process exploited for the "foie gras" production in mule ducks. To better understand the mechanisms underlying its development, the physiological responses of mule ducks overfed with corn for a duration of 11 days were analyzed. A kinetic analysis of glucose and lipid metabolism and cell protection mechanisms was performed on 96 male mule ducks during overfeeding with three sampling times (after the 4th, the 12th, and the 22nd meal). Read More

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February 2020

CYPs-mediated drug-drug interactions on psoralidin, isobavachalcone, neobavaisoflavone and daidzein in rats liver microsomes.

Food Chem Toxicol 2020 Feb 21;136:111027. Epub 2019 Dec 21.

National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng, 475004, China; Joint International Research Laboratory of Food & Medicine, Henan Province, Henan University, Kaifeng, 475004, China. Electronic address:

The incubation system of CYP2E1 and CYP3A4 enzymes in rat liver microsomes was established to investigate the effects of psoralidin, isobavachalcone, neobavaisoflavone and daidzein from Fructus Psoraleae in vitro. The relevant metabolites were measured by the method of high performance liquid chromatography (HPLC), after probe substrates of 4-nitrophenol, testosterone and the drugs at different concentrations were added to the incubation systems. In addition, real-time RT-PCR was performed to determine the effect of psoralidin, neobavaisoflavone and daidzein on the mRNA expression of CYP3A4 in rat liver. Read More

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February 2020

Time-Dependent Changes in Urinary Metabolome Before and After Intensive Phase Tuberculosis Therapy: A Pharmacometabolomics Study.

OMICS 2019 11 15;23(11):560-572. Epub 2019 Oct 15.

Human Metabolomics, North-West University, Potchefstroom, South Africa.

Pharmacometabolomics is a rapidly emerging omics science signaling the convergence of clinical pharmacology, metabolomics, precision medicine, and biomarker research. Tuberculosis (TB) treatment outcomes have complex biological, environmental, and social determinants and thus, represent a promising application of pharmacometabolomics. In samples of 23 patients undergoing intensive phase TB therapy for 4 weeks, we identified drug-induced host-metabolome variations before and at repeated time intervals post-treatment: (1) an overall reduction in the oxidative stress levels over the course of TB treatment; (2) a time-dependent induction and inhibition of several enzymes in response to the drugs (CYP2E1, CYP3A4, alcohol dehydrogenase, and aminocarboxymuconate-semialdehyde decarboxylase), and altered oxidative stress levels (aconitase, formylglycine-generating enzyme, α-ketoglutarate dehydrogenase, and succinate-semialdehyde dehydrogenase); (3) an upregulated urea cycle; and (4) altered insulin production. Read More

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November 2019