Expression of Cytochrome P450 (CYP) Enzymes in Human Nonpigmented Ciliary Epithelial Cells: Induction of CYP1B1 Expression by TCDD

2009 ◽  
Vol 50 (7) ◽  
pp. 3099 ◽  
Author(s):  
Marjo Volotinen ◽  
Jukka Ma¨enpa¨a¨ ◽  
Esko Kankuri ◽  
Olli Oksala ◽  
Olavi Pelkonen ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Epithelial Cells ◽  
Cyp Enzymes ◽  
Nonpigmented Ciliary Epithelial

scholarly journals The Effect of Chronic Iloperidone Treatment on Cytochrome P450 Expression and Activity in the Rat Liver: Involvement of Neuroendocrine Mechanisms

2021 ◽  
Vol 22 (16) ◽  
pp. 8447
Author(s):  
Przemysław J. Danek ◽  
Wojciech Kuban ◽  
Władysława A. Daniel
Keyword(s):  
Cytochrome P450 ◽  
Rat Liver ◽  
Combined Treatment ◽  
Pharmacological Therapy ◽  
Mental Wellbeing ◽  
Cyp Enzymes ◽  
P450 Expression ◽  
Male Wistar Rats ◽  
Expression And Activity

In order to achieve a desired therapeutic effect in schizophrenia patients and to maintain their mental wellbeing, pharmacological therapy needs to be continued for a long time, usually from the onset of symptoms and for the rest of the patients’ lives. The aim of our present research is to find out the in vivo effect of chronic treatment with atypical neuroleptic iloperidone on the expression and activity of cytochrome P450 (CYP) in rat liver. Male Wistar rats received a once-daily intraperitoneal injection of iloperidone (1 mg/kg) for a period of two weeks. Twenty-four hours after the last dose, livers were excised to study cytochrome P450 expression (mRNA and protein) and activity, pituitaries were isolated to determine growth hormone-releasing hormone (GHRH), and blood was collected for measuring serum concentrations of hormones and interleukin. The results showed a broad spectrum of changes in the expression and activity of liver CYP enzymes, which are important for drug metabolism (CYP1A, CYP2B, CYP2C, and CYP3A) and xenobiotic toxicity (CYP2E1). Iloperidone decreased the expression and activity of CYP1A2, CP2B1/2, CYP2C11, and CYP3A1/2 enzymes but increased that of CYP2E1. The CYP2C6 enzyme remained unchanged. At the same time, the level of GHRH, GH, and corticosterone decreased while that of T3 increased, with no changes in IL-2 and IL-6. The presented results indicate neuroendocrine regulation of the investigated CYP enzymes during chronic iloperidone treatment and suggest a possibility of pharmacokinetic/metabolic interactions produced by the neuroleptic during prolonged combined treatment with drugs that are substrates of iloperidone-affected CYP enzymes.

PGE2, Ca2+, and cAMP mediate ATP activation of Cl− channels in pigmented ciliary epithelial cells

2001 ◽  
Vol 281 (5) ◽  
pp. C1614-C1623 ◽  
Author(s):  
Johannes C. Fleischhauer ◽  
Claire H. Mitchell ◽  
Kim Peterson-Yantorno ◽  
Miguel Coca-Prados ◽  
Mortimer M. Civan
Keyword(s):  
Intraocular Pressure ◽  
Epithelial Cells ◽  
Aqueous Humor ◽  
Second Messengers ◽  
Atp Release ◽  
Channel Activity ◽  
Atp Assay ◽  
Intracellular Ca ◽  
Cl Channels ◽  
Nonpigmented Ciliary Epithelial

Purines regulate intraocular pressure. Adenosine activates Cl− channels of nonpigmented ciliary epithelial cells facing the aqueous humor, enhancing secretion. Tamoxifen and ATP synergistically activate Cl− channels of pigmented ciliary epithelial (PE) cells facing the stroma, potentially reducing net secretion. The actions of nucleotides alone on Cl− channel activity of bovine PE cells were studied by electronic cell sorting, patch clamping, and luciferin/luciferase ATP assay. Cl−channels were activated by ATP > UTP, ADP, and UDP, but not by 2-methylthio-ATP, all at 100 μM. UTP triggered ATP release. The second messengers Ca2+, prostaglandin (PG)E2, and cAMP activated Cl− channels without enhancing effects of 100 μM ATP. Buffering intracellular Ca2+activity with 1,2-bis(2-aminophenoxy)ethane- N,N,N′,N′- tetraacetic acid or blocking PGE2 formation with indomethacin inhibited ATP-triggered channel activation. The Rp stereoisomer of 8-bromoadenosine 3′,5′-cyclic monophosphothioate inhibited protein kinase A activity but mimicked 8-bromoadenosine 3′,5′-cyclic monophosphate. We conclude that nucleotides can act at >1 P2Y receptor to trigger a sequential cascade involving Ca2+, PGE2, and cAMP. cAMP acts directly on Cl−channels of PE cells, increasing stromal release and potentially reducing net aqueous humor formation and intraocular pressure.

scholarly journals Alteration in Inflammatory Responses and Cytochrome P450 Expression of Porcine Jejunal Cells by Drinking Water Supplements

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Orsolya Palócz ◽  
Géza Szita ◽  
György Csikó
Keyword(s):  
Gene Expression ◽  
Drinking Water ◽  
Cytochrome P450 ◽  
Epithelial Cells ◽  
Fulvic Acid ◽  
Intestinal Epithelial Cells ◽  
Feed Additives ◽  
Feed Additive ◽  
Mrna Levels ◽  
Intestinal Epithelial

The intestinal epithelium is the first determining barrier to the drugs administered per os. Cytochrome P450 (CYP) enzymes are substantial in the initial step of xenobiotic metabolism; therefore, intestinal CYP enzyme activities could be an important influencing factor of the oral utilization of xenobiotic substances. In this study, the effect of four drinking water supplements on CYP mRNA levels of porcine intestinal epithelial cells was examined. Further goal of the study is to describe the effect of these feed additives on the proinflammatory response of the LPS-treated enterocytes. The nontransformed porcine intestinal epithelial cells (IPEC-J2) were grown on six-well polyester membrane inserts. Cell cultures were treated with LPS (10 μg/ml), β-glucan (5 and 50 μg/ml), sanguinarine-containing additive (5 and 50 μg/ml), drinking water acidifier (0.1 and 1 μl/ml), and fulvic acid (25 and 250 μg/ml) for 1 hour. Cells were washed with culture medium and incubated for additional 1 h before total RNA isolation. IL-6, IL-8, TNF-α, HSP70, CYP1A1, CYP1A2, and CYP3A29 mRNA levels were measured. The LPS treatment upregulated the gene expression of IL-8 and TNF-α. The relative gene expression of IL-6 remained unchanged and TNF-α and HSP70 were downregulated after the treatment with each feed additive. CYP1A1 and CYP1A2 expressions increased after sanguinarine-containing solution, fulvic acid, and drinking water acidifier treatment. None of the treatments changed the gene expression of CYP3A29, responsible for the metabolism of the majority of drug substances used in swine industry. The feed additive substances inhibited the expression of proinflammatory mediators HSP70 and TNF-α; however, β-glucan and fulvic acid elevated the production of the chemokine IL-8 mRNA in endotoxin-treated enterocytes. All acidic supplements increased the expression of CYP1A1 gene; their constituents may serve as a ligand of CYP1A1 nuclear receptors.

scholarly journals Nonpigmented Ciliary Epithelial Cells Respond to Acetazolamide by a Soluble Adenylyl Cyclase Mechanism

2014 ◽  
Vol 55 (1) ◽  
pp. 187 ◽  
Author(s):  
Mohammad Shahidullah ◽  
Amritlal Mandal ◽  
Guojun Wei ◽  
Lonny R. Levin ◽  
Jochen Buck ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Adenylyl Cyclase ◽  
Soluble Adenylyl Cyclase ◽  
Nonpigmented Ciliary Epithelial

scholarly journals The role of cytochrome P450 (CYP) enzymes in hyperoxic lung injury

2020 ◽  
pp. 1-8
Author(s):  
Rachel Stading ◽  
Xanthi Couroucli ◽  
Krithika Lingappan ◽  
Bhagavatula Moorthy
Keyword(s):  
Cytochrome P450 ◽  
Lung Injury ◽  
Cyp Enzymes ◽  
Hyperoxic Lung Injury

scholarly journals Comprehensive In Vitro Analysis of Voriconazole Inhibition of Eight Cytochrome P450 (CYP) Enzymes: Major Effect on CYPs 2B6, 2C9, 2C19, and 3A

2008 ◽  
Vol 53 (2) ◽  
pp. 541-551 ◽  
Author(s):  
Seongwook Jeong ◽  
Phuong D. Nguyen ◽  
Zeruesenay Desta
Keyword(s):  
Cytochrome P450 ◽  
Liver Microsomes ◽  
Competitive Inhibitor ◽  
Major Effect ◽  
Cyp Enzymes ◽  
Human Cytochrome ◽  
Vitro Analysis ◽  
In Vitro Analysis

ABSTRACT Voriconazole is an effective antifungal drug, but adverse drug-drug interactions associated with its use are of major clinical concern. To identify the mechanisms of these interactions, we tested the inhibitory potency of voriconazole with eight human cytochrome P450 (CYP) enzymes. Isoform-specific probes were incubated with human liver microsomes (HLMs) (or expressed CYPs) and cofactors in the absence and the presence of voriconazole. Preincubation experiments were performed to test mechanism-based inactivation. In pilot experiments, voriconazole showed inhibition of CYP2B6, CYP2C9, CYP2C19, and CYP3A (half-maximal [50%] inhibitory concentrations, <6 μM); its effect on CYP1A2, CYP2A6, CYP2C8, and CYP2D6 was marginal (<25% inhibition at 100 μM voriconazole). Further detailed experiments with HLMs showed that voriconazole is a potent competitive inhibitor of CYP2B6 (Ki < 0.5), CYP2C9 (Ki = 2.79 μM), and CYP2C19 (Ki = 5.1 μM). The inhibition of CYP3A by voriconazole was explained by noncompetitive (Ki = 2.97 μM) and competitive (Ki = 0.66 μM) modes of inhibition. Prediction of the in vivo interaction of voriconazole from these in vitro data suggests that voriconazole would substantially increase the exposure of drugs metabolized by CYP2B6, CYP2C9, CYP2C19, and CYP3A. Clinicians should be aware of these interactions and monitor patients for adverse effects or failure of therapy.

scholarly journals Impact of Panax ginseng and Ginkgo biloba extracts on expression level of transcriptional factors and xenobiotic-metabolizing cytochrome P450 enzymes

2016 ◽  
Vol 62 (1) ◽  
pp. 42-54 ◽  
Author(s):  
Anna Bogacz ◽  
Monika Karasiewicz ◽  
Karolina Dziekan ◽  
Danuta Procyk ◽  
Małgorzata Górska-Paukszta ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Panax Ginseng ◽  
Ginkgo Biloba ◽  
Mrna Level ◽  
Transcriptional Factors ◽  
Expression Level ◽  
Herbal Remedies ◽  
Cytochrome P450 Enzymes ◽  
Ginseng Extract ◽  
Cyp Enzymes

Summary Introduction: Despite widespread use of Panax ginseng and Ginkgo biloba, the data on the safety as well as herb-drug interactions are very limited. Therefore, we postulate that P. ginseng and G. biloba may modulate the activity and content of cytochrome P450 isozymes involved in the biotransformation of diverse xenobiotic substances. Objective: The aim of our study was to determine the influence of herbal remedies on the expression level of CYP enzymes and transcriptional factors. Methods: Male Wistar rats were given standardized Panax ginseng (30 mg/kg p.o.) or standardized Ginkgo biloba (200 mg/kg p.o.) for 3 and 10 days. The expression in liver tissue was analyzed by realtime PCR method. Results: Our results showed a decrease of CYP3A1 (homologue to human CYP3A4) mRNA level after P. ginseng extract treatment. The CYP2C6 (homologue to human CYP2C9) expression was also reduced. Additionally, after 10 days of the treatment with P. ginseng an increase of CYP1A1 (homologue to human CYP1A1) and CYP1A2 (homologue to human CYP1A2) expression was observed. Moreover, G. biloba extract also caused an increase of expression level for CYP1A1, CYP2C6, CYP3A1 and CYP3A2. Conclusion: Our findings suggest that herbal extracts can modulate the expression of transcriptional factors and CYP enzymes involved in xenobiotic metabolism and chemical carcinogenesis.

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