scholarly journals Differential Modulation of Gene Expression Encoding Hepatic and Renal Xenobiotic Metabolizing Enzymes by an Aspalathin-Enriched Rooibos Extract and Aspalathin

Planta Medica ◽  
2018 ◽  
Vol 85 (01) ◽  
pp. 6-13
Author(s):  
Sameega Abrahams ◽  
Sedicka Samodien ◽  
Mariska Lilly ◽  
Elizabeth Joubert ◽  
Wentzel Gelderblom
Keyword(s):  
Gene Expression ◽  
Cytochrome P450 ◽  
Tissue Type ◽  
Differential Modulation ◽  
Primary Hepatocytes ◽  
Glutathione S Transferase ◽  
Metabolizing Enzymes ◽  
Xenobiotic Metabolizing Enzymes ◽  
Genes Encoding

AbstractModulation of the expression of hepatic and renal genes encoding xenobiotic metabolizing enzymes by an aspalathin-enriched green rooibos (Aspalathus linearis) extract (GRE) was investigated in the liver and kidneys of F344 rats following dietary exposure of 28 d, as well as selected xenobiotic metabolizing genes in rat primary hepatocytes. In the liver, GRE upregulated genes (p < 0.05) encoding aldehyde dehydrogenase, glucose phosphate isomerase, and cytochrome P450 while 17β-hydroxysteroid dehydrogenase 2 (Hsd17β2) was downregulated. In primary hepatocytes, GRE lacked any effect, while aspalathin downregulated Hsd17β2, mimicking the effect of GRE in vivo, and upregulated catechol-O-methyl transferase and marginally (p < 0.1) cytochrome P450 2e1. In the kidneys, GRE upregulated (p < 0.05) genes encoding the phase II xenobiotic metabolism enzymes, glutathione-S-transferase mµ and microsomal glutathione-S-transferase, while downregulating genes encoding the ATP binding cassette transporter, cytochrome P450, gamma glutamyltransferase 1, and N-acetyltransferase 1. Differential modulation of the expression of xenobiotic metabolizing genes in vivo and in vitro by GRE is dose-related, duration of exposure, the tissue type, and interactions between specific polyphenol and/or combinations thereof. Aspalathin is likely to be responsible for the downregulation of estradiol and testosterone catabolism by GRE in the liver. The differential gene expression by GRE in the liver and kidneys could, depending on the duration exposure and dose utilized, determine the safe use of such an extract in humans for specific health and/or disease outcomes.

scholarly journals Changes in cytochrome P450 gene expression and enzyme activity induced by xenobiotics in rabbits in vivo and in vitro

2017 ◽  
Vol 25 (2) ◽  
pp. 173 ◽  
Author(s):  
Orsolya Palócz ◽  
Orsolya Farkas ◽  
Paul Clayton ◽  
György Csikó
Keyword(s):  
Gene Expression ◽  
Cytochrome P450 ◽  
Toxicity Testing ◽  
Xenobiotic Metabolism ◽  
Cytochrome P450 Enzyme ◽  
Primary Hepatocytes ◽  
Short Term ◽  
P450 Gene

As considerable inter-species differences exist in xenobiotic metabolism, developing new pharmaceutical therapies for use in different species is fraught with difficulties. For this reason, very few medicines have been registered for use in rabbits, despite their importance in inter alia meat and fur production. We have developed a rapid and sensitive screening system for drug safety in rabbits based on cytochrome P450 enzyme assays, specifically CYP1A1, CYP1A2 and CYP3A6, employing an adaptation of the luciferin-based clinical assay currently used in human drug screening. Short-term (4-h) cultured rabbit primary hepatocytes were treated with a cytochrome inducer (phenobarbital) and 2 inhibitors (alpha-naphthoflavone and ketoconazole). In parallel, and to provide verification, New Zealand white rabbits were dosed with 80 mg/kg phenobarbital or 40 mg/kg ketoconazole for 3 d. Ketoconazole significantly increased CYP3A6 gene expression and decreased CYP3A6 activity both in vitro and in vivo. CYP1A1 activity was decreased by ketoconazole in vitro and increased in vivo. This is the first report of the inducer effect of ketoconazole on rabbit cytochrome isoenzymes in vivo. Our data support the use of a luciferin-based assay in short-term primary hepatocytes as an appropriate tool for xenobiotic metabolism assays and short-term toxicity testing in rabbits.<p> </p>

Effects of short-term saffron (Crocus sativus L.) intake on the in vivo activities of xenobiotic metabolizing enzymes in healthy volunteers

2019 ◽  
Vol 130 ◽  
pp. 32-43 ◽  
Author(s):  
Elias Begas ◽  
Maria Bounitsi ◽  
Thomas Kilindris ◽  
Evangelos Kouvaras ◽  
Konstantinos Makaritsis ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Crocus Sativus ◽  
Short Term ◽  
Metabolizing Enzymes ◽  
Xenobiotic Metabolizing Enzymes ◽  
Crocus Sativus L

scholarly journals Effects of berberine on the recovery of rat liver xenobiotic-metabolizing enzymes after partial hepatectomy

2015 ◽  
Vol 61 (3) ◽  
pp. 381-383 ◽  
Author(s):  
I.V. Zverinsky ◽  
H.G. Zverinskaya ◽  
I.P. Sutsko ◽  
P.G. Telegin ◽  
A.G. Shlyahtun
Keyword(s):  
Cytochrome P450 ◽  
Partial Hepatectomy ◽  
Rat Liver ◽  
Compensatory Growth ◽  
Metabolizing Enzymes ◽  
Xenobiotic Metabolizing Enzymes ◽  
Recovery Processes

We have studied the effect of berberine on the recovery processes of liver xenobiotic-metabolizing function during its compensatory growth after 70% partial hepatectomy. It was found the hepatic ability to metabolize foreign substances are not restored up to day 8. Administration of berberine (10 mg/kg intraperitoneally) for 6 days led to normalization of both cytochrome P450-dependent and flavin-containing monooxygenases. It is suggested that in the biotransformation of berberine involved not only cytochrome P450, but also flavin-containing monooxygenases.

scholarly journals Effect of mild restriction of food intake on gene expression profile in the liver of young rats: reference data for in vivo nutrigenomics study

2010 ◽  
Vol 104 (7) ◽  
pp. 941-950 ◽  
Author(s):  
Kenji Saito ◽  
Yutaka Ohta ◽  
Manabu Sami ◽  
Tomomasa Kanda ◽  
Hisanori Kato
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Fatty Acid Synthase ◽  
Reference Data ◽  
Global Gene Expression ◽  
Energy Restriction ◽  
Genes Encoding

Recent transcriptomics studies on the effect of long-term or severe energy restriction (ER) have revealed that many genes are dynamically modulated by this condition in rodents. The present study was conducted to define the global gene expression profile in response to mild ER treatment. Growing rats were fed with reduced amount of diet (5–30 % ER) for 1 week or 1 month. Using DNA microarray analysis of the liver, seventy-two genes that were consistently changed through the different ER levels were identified. Many were related to lipid metabolism including genes encoding key enzymes such as carnitine palmitoyltransferase 1 and fatty acid synthase. Interestingly, a number of genes were altered even by 5 % ER for 1 week where no differences in weight gain were observed. The information obtained in the present study can be used as a valuable reference data source in the transcriptomics studies of food and nutrition in which subtle differences in food intake sometimes hinder appropriate interpretation of the data.

scholarly journals Tumorigenicity of simian virus 40-hepatocyte cell lines: effect of in vitro and in vivo passage on expression of liver-specific genes and oncogenes.

1988 ◽  
Vol 8 (10) ◽  
pp. 4492-4501 ◽  
Author(s):  
C D Woodworth ◽  
J W Kreider ◽  
L Mengel ◽  
T Miller ◽  
Y L Meng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Cell ◽  
Cell Lines ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Tumor Cell Lines ◽  
Glutathione S Transferase

Five simian virus 40 (SV40)-hepatocyte cell lines were examined for tumorigenicity and the effect of in vitro passage on the expression of four liver-specific genes (albumin, transferrin, alpha 1-antitrypsin, and phosphoenolpyruvate carboxykinase), two oncogenes (c-Ha-ras and c-raf), and two genes associated with hepatocarcinogenesis (alpha-fetoprotein and placental-type glutathione-S-transferase). At low passage (12 to 22), all five cell lines expressed the four liver-specific genes at levels similar to those in the liver and were not tumorigenic or were weakly tumorigenic. At high passage (33 to 61), the cell lines formed carcinomas, and four out of five cell lines produced primary tumors that metastasized. At least two cell lines produced well-differentiated hepatocellular carcinomas that expressed liver-specific RNAs. Levels of expression of liver-specific genes changed with time in culture. Some of the changes in liver-specific gene expression in the tumor tissue (such as for the phosphoenolpyruvate carboxykinase gene) paralleled those that occurred with in vitro passage, while other changes (such as for the albumin gene) did not parallel those that occurred with in vitro passage. Correlations between enhanced expression of c-Ha-ras and tumorigenic potential and between the process of SV40 immortalization and induced expression of c-raf and glutathione-S-transferase-P were observed. Induction of alpha-fetoprotein was detected with in vitro and in vivo passage only in the CWSV14 cell line and was paralleled by diminished albumin expression. In conclusion, we developed a model system with five SV40-hepatocyte cell lines, tumors induced by them, and tumor cell lines to examine changes in gene expression that accompany the progression from a normal cell to a hepatocellular carcinoma. Because the SV40-hepatocyte cell lines and tumor cell lines remain highly differentiated and vary in the magnitude of expression of specific genes, they can be used to study the molecular mechanisms regulating gene expression, in particular those regulating specific genes associated with differentiation.

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