Functional Coupling of ATP-binding Cassette TransporterAbcb6to Cytochrome P450 Expression and Activity in Liver

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.

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Detoxification of ivermectin by ATP binding cassette transporter C4 and cytochrome P450 monooxygenase 6CJ1 in the human body louse, Pediculus humanus humanus

Insect Molecular Biology ◽

10.1111/imb.12348 ◽

2017 ◽

Vol 27 (1) ◽

pp. 73-82 ◽

Cited By ~ 8

Author(s):

J. H. Kim ◽

K. J. Gellatly ◽

B. Lueke ◽

M. Kohler ◽

R. Nauen ◽

...

Keyword(s):

Cytochrome P450 ◽

Human Body ◽

Cytochrome P450 Monooxygenase ◽

Atp Binding ◽

P450 Monooxygenase ◽

Body Louse ◽

Pediculus Humanus ◽

Atp Binding Cassette Transporter ◽

Human Body Louse ◽

Atp Binding Cassette

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Isoform-specific regulation of cytochrome P450 expression and activity by estradiol in female rats

Biochemical Pharmacology ◽

10.1016/j.bcp.2010.12.019 ◽

2011 ◽

Vol 81 (6) ◽

pp. 777-782 ◽

Cited By ~ 17

Author(s):

Su-Young Choi ◽

Liam Fischer ◽

Kyunghee Yang ◽

Hyejin Chung ◽

Hyunyoung Jeong

Keyword(s):

Cytochrome P450 ◽

Female Rats ◽

P450 Expression ◽

Specific Regulation ◽

Expression And Activity

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Activation of 5-HT1A Receptors in the Hypothalamic Paraventricular Nuclei Negatively Regulates Cytochrome P450 Expression and Activity in Rat Liver

Drug Metabolism and Disposition ◽

10.1124/dmd.117.079632 ◽

2018 ◽

Vol 46 (6) ◽

pp. 786-793 ◽

Cited By ~ 5

Author(s):

Ewa Bromek ◽

Marta Rysz ◽

Anna Haduch ◽

Jacek Wójcikowski ◽

Władysława A. Daniel

Keyword(s):

Cytochrome P450 ◽

Rat Liver ◽

Paraventricular Nuclei ◽

P450 Expression ◽

Expression And Activity ◽

Hypothalamic Paraventricular Nuclei

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Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice

Clinical Chemistry ◽

10.1373/clinchem.2016.264986 ◽

2017 ◽

Vol 63 (7) ◽

pp. 1204-1213 ◽

Cited By ~ 22

Author(s):

Maja Matic ◽

Saskia N de Wildt ◽

Dick Tibboel ◽

Ron H N van Schaik

Keyword(s):

Cytochrome P450 ◽

Treatment Guidelines ◽

Twin Studies ◽

Atp Binding ◽

Clinical Implementation ◽

Large Variability ◽

Gated Channel ◽

Cytochrome P450 Family ◽

Opioid Efficacy ◽

Atp Binding Cassette

Abstract BACKGROUND The use of opioids to alleviate pain is complicated by the risk of severe adverse events and the large variability in dose requirements. Pharmacogenetics (PGx) could possibly be used to tailor pain medication based on an individual's genetic background. Many potential genetic markers have been described, and the importance of genetic predisposition in opioid efficacy and toxicity has been demonstrated in knockout mouse models and human twin studies. Such predictors are especially of value for neonates and young children, in whom the assessment of efficacy or side effects is complicated by the inability of the patient to communicate this properly. The current problem is determining which of the many potential candidates to focus on for clinical implementation. CONTENT We systematically searched publications on PGx for opioids in 5 databases, aiming to identify PGx markers with sufficient robust data and high enough occurrence for potential clinical application. The initial search yielded 4257 unique citations, eventually resulting in 852 relevant articles covering 24 genes. From these genes, we evaluated the evidence and selected the most promising 10 markers: cytochrome P450 family 2 subfamily D member 6 (CYP2D6), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), cytochrome P450 family 3 subfamily A member 5 (CYP3A5), UDP glucuronosyltransferase family 2 member B7 (UGT2B7), ATP binding cassette subfamily B member 1 (ABCB1), ATP binding cassette subfamily C member 3 (ABCC3), solute carrier family 22 member 1 (SLC22A1), opioid receptor kappa 1 (OPRM1), catechol-O-methyltransferase (COMT), and potassium voltage-gated channel subfamily J member 6 (KCNJ6). Treatment guidelines based on genotype are already available only for CYP2D6. SUMMARY The application of PGx in the management of pain with opioids has the potential to improve therapy. We provide a shortlist of 10 genes that are the most promising markers for clinical use in this context.

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In vitro effects of rebaudioside A, stevioside and steviol on porcine cytochrome p450 expression and activity

Food Chemistry ◽

10.1016/j.foodchem.2018.03.055 ◽

2018 ◽

Vol 258 ◽

pp. 245-253 ◽

Cited By ~ 6

Author(s):

Rebekka Thøgersen ◽

Bjørn Petrat-Melin ◽

Galia Zamaratskaia ◽

Kai Grevsen ◽

Jette Feveile Young ◽

...

Keyword(s):

Cytochrome P450 ◽

Rebaudioside A ◽

P450 Expression ◽

In Vitro Effects ◽

Expression And Activity

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BDE-209 and TCDD Modulate the Expression and Activity of ATP-Binding Cassette (ABC) Transporters in Murine Melanoma Cells (B16-F1)

10.31487/j.ijcst.2021.02.01 ◽

2021 ◽

pp. 1-7

Author(s):

Ciro A. Oliveira Ribeiro ◽

Micheli de Marchi ◽

Erick E. Moggio ◽

Francisco Filipak Neto ◽

Patricia E.M. Brito ◽

...

Keyword(s):

Tumor Cells ◽

Abc Transporters ◽

Environmental Pollutants ◽

Cancer Prognosis ◽

Atp Binding ◽

Protein Activity ◽

Murine Melanoma ◽

Expression And Activity ◽

Bde 209 ◽

Atp Binding Cassette

Persistent organic pollutants (POPs) may alter tumor cells phenotype, possibly increasing malignancy, but there is a lack of studies investigating the mechanisms by which POPs may affect tumor cells. The ATP-Binding Cassette (ABC) transporter proteins are a widely studied component of drug resistance and tumor progression. We hypothesized that the levels of BDE-209 and TCDD detected in human serum can modulate the gene expression or activity of ATP-binding cassette (ABC) transporters in murine melanoma (B16-F1) cells. In this study, we observed an upregulation of the ABCB1 and ABCC4 (24 h) genes followed by an increased protein activity after BDE-209 15 day-exposure. We also observed that cells exposed to TCDD showed an upregulation of ABCB5, ABCC1 and ABCC4 genes (24 h) and change of protein activity after 15 days of exposure. These findings suggest that BDE-209 and TCDD can regulate the phenotype of B16-F1 cells by interfering with the expression and activity of ATP-binding cassette (ABC) transporters. This investigation revealed that environmental pollutants might intervene and modify cells’ resistance to chemotherapy and cancer prognosis.

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