Human placental cytochrome P450 and quinone reductase enzyme induction in relation to maternal smoking

1995 ◽  
Vol 7 (6) ◽  
pp. 1521 ◽  
Author(s):  
AG Boden ◽  
PG Bush ◽  
MD Burke ◽  
DR Abramovich ◽  
P Aggett ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Maternal Smoking ◽  
High Performance ◽  
Smoking Habit ◽  
Placental Tissue ◽  
Maternal Plasma ◽  
Quinone Reductase ◽  
Polycyclic Aromatic ◽  
Plasma Cotinine

Components of cigarette smoke such as cadmium and polycyclic aromatic hydrocarbons have been shown to induce quinone reductase (QR) activity in placental explants. This study examines the relationship of maternal smoking habit and maternal plasma cotinine concentration with the activities in vitro of both QR and the cytochrome P450 (CYP1A) marker ethoxyresorufin O-deethylase (EROD) in placental tissue. Maternal plasma samples were taken at Week 34 of gestation, and placental tissues were obtained at term. Plasma cotinine concentrations were determined by high-performance liquid chromatography. Trophoblast cytosolic QR and microsomal EROD activities were measured by resazurin reduction and ethoxyresorufin O-dealkylation respectively. QR activity was inhibited 70% by a mixture of dicoumarol (1 microM) and rutin (20 microM). Plasma cotinine concentrations correlated significantly (P < 0.001) with both declared smoking rate (r = 0.67, N = 37) and placental EROD activity (r = 0.63, N = 36), but not with QR activity, whether measured as total QR activity or specifically as either DT-diaphorase or carbonyl reductase. It is concluded that smoking up to 40 cigarettes per day induces EROD but does not affect QR activity in the placenta at term.

scholarly journals Enzymatic activity in turkey, duck, quail and chicken liver microsomes against four human cytochrome P450 prototype substrates and aflatoxin B1

2011 ◽  
Vol 1 (1) ◽  
pp. 4 ◽  
Author(s):  
Hansen W. Murcia ◽  
Gonzalo J. Díaz ◽  
Sandra Milena Cepeda
Keyword(s):  
Cytochrome P450 ◽  
Aflatoxin B1 ◽  
Enzyme Activities ◽  
High Performance ◽  
Biochemical Characterization ◽  
Liver Microsomes ◽  
Cytochrome P450 Enzymes ◽  
Catalytic Rate

Cytochrome P450 enzymes (CYP) are a group of monooxygenases able to biotransform several kinds of xenobiotics including aflatoxin B1 (AFB1), a highly toxic mycotoxin. These enzymes have been widely studied in humans and others mammals, but there is not enough information in commercial poultry species about their biochemical characteristics or substrate specificity. The aim of the present study was to identify CYPs from avian liver microsomes with the use of prototype substrates specific for human CYP enzymes and AFB1. Biochemical characterization was carried out in vitro and biotransformation products were detected by high-performance liquid chromatography (HPLC). Enzymatic constants were calculated and comparisons between turkey, duck, quail and chicken activities were done. The results demonstrate the presence of four avian ortholog enzyme activities possibly related with a CYP1A1, CYP1A2, CYP2A6 (activity not previously identified) and CYP3A4 poultry orthologs, respectively. Large differences in enzyme kinetics specific for prototype substrates were found among the poultry species studied. Turkey liver microsomes had the highest affinity and catalytic rate for AFB1 whereas chicken enzymes had the lowest affinity and catalytic rate for the same substrate. Quail and duck microsomes showed intermediate values. These results correlate well with the known in vivo sensitivity for AFB1 except for the duck. A high correlation coefficient between 7-ethoxyresorufin-Odeethylase (EROD) and 7-methoxyresorufin- O-deethylase (MROD) activities was found in the four poultry species, suggesting that these two enzymatic activities might be carried out by the same enzyme. The results of the present study indicate that four prototype enzyme activities are present in poultry liver microsomes, possibly related with the presence of three CYP avian orthologs. More studies are needed in order to further characterize these enzymes.

In vitro inhibitory effects of glucosamine, chondroitin and diacerein on human hepatic CYP2D6

2021 ◽  
Vol 36 (4) ◽  
pp. 259-270
Author(s):  
Boon Hooi Tan ◽  
Nafees Ahemad ◽  
Yan Pan ◽  
Uma Devi Palanisamy ◽  
Iekhsan Othman ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
High Performance ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Time Curve ◽  
Clinical Drugs ◽  
Inhibition Potencies ◽  
P450 2D6

Abstract Objectives Glucosamine, chondroitin and diacerein are natural compounds commonly used in treating osteoarthritis. Their concomitant intake may trigger drug–natural product interactions. Cytochrome P450 (CYP) has been implicated in such interactions. Cytochrome P450 2D6 (CYP2D6) is a major hepatic CYP involved in metabolism of 25% of the clinical drugs. This study aimed to investigate the inhibitory effect of these antiarthritic compounds on CYP2D6. Methods CYP2D6 was heterologously expressed in Escherichia coli. CYP2D6–antiarthritic compound interactions were studied using in vitro enzyme kinetics assay and molecular docking. Results The high-performance liquid chromatography (HPLC)-based dextromethorphan O-demethylase assay was established as CYP2D6 marker. All glucosamines and chondroitins weakly inhibited CYP2D6 (IC50 values >300 µM). Diacerein exhibited moderate inhibition with IC50 and K i values of 34.99 and 38.27 µM, respectively. Its major metabolite, rhein displayed stronger inhibition potencies (IC50=26.22 μM and K i =32.27 μM). Both compounds exhibited mixed-mode of inhibition. In silico molecular dockings further supported data from the in vitro study. From in vitro–in vivo extrapolation, rhein presented an area under the plasma concentration-time curve (AUC) ratio of 1.5, indicating low potential to cause in vivo inhibition. Conclusions Glucosamine, chondroitin and diacerein unlikely cause clinical interaction with the drug substrates of CYP2D6. Rhein, exhibits only low potential to cause in vivo inhibition.

Genotype and fetal size affect maternal­–fetal amino acid status and fetal endocrinology in Large White×Landrace and Meishan pigs

2013 ◽  
Vol 25 (2) ◽  
pp. 439 ◽  
Author(s):  
Cheryl J. Ashworth ◽  
Margaret O. Nwagwu ◽  
Harry J. McArdle
Keyword(s):  
Amino Acid ◽  
Plasma Concentrations ◽  
Placental Tissue ◽  
Maternal Plasma ◽  
Plasma Amino Acid ◽  
Large White ◽  
Fetal Plasma ◽  
Acid Status ◽  
Fetal Size

This study compared maternal plasma amino acid concentrations, placental protein secretion in vitro and fetal body composition and plasma amino acid and hormone concentrations in feto–placental units from the smallest and a normally-sized fetus carried by Large White × Landrace or Meishan gilts on Day 100 of pregnancy. Compared with Large White × Landrace, Meishan placental tissue secreted more protein and Meishan fetuses contained relatively more fat and protein, but less moisture. Fetal plasma concentrations of insulin, triiodothryonine, thyroxine and insulin-like growth factor (IGF)-II were higher in Meishan than Large White × Landrace fetuses. In both breeds, fetal cortisol concentrations were inversely related to fetal size, whereas concentrations of IGF-I were higher in average-sized fetuses. Concentrations of 10 amino acids were higher in Large White × Landrace than Meishan gilts, while glutamine concentrations were higher in Meishan gilts. Concentrations of alanine, aspartic acid, glutamic acid and threonine were higher in Meishan than Large White × Landrace fetuses. Average-sized fetuses had higher concentrations of asparagine, leucine, lysine, phenylalanine, threonine, tyrosine and valine than the smallest fetus. This study revealed novel genotype and fetal size differences in porcine maternal–fetal amino acid status and fetal hormone and metabolite concentrations.

scholarly journals An in vitro affinity-based method for studying herb–drug interactions for direct identification of cytochrome P450 1A2, 3A4, and 2C9 specific ligands from herbal extracts using ultrafiltration-high performance liquid chromatography

RSC Advances ◽  
2018 ◽  
Vol 8 (16) ◽  
pp. 8944-8949 ◽  
Author(s):  
Zhiqiang Wang ◽  
Seung Hwan Hwang ◽  
Guanglei Zuo ◽  
Set Byeol Kim ◽  
Soon Sung Lim
Keyword(s):  
High Performance Liquid Chromatography ◽  
Cytochrome P450 ◽  
Liquid Chromatography ◽  
Natural Product ◽  
High Performance ◽  
Target System ◽  
Herbal Extracts ◽  
Cytochrome P450 1A2 ◽  
Direct Identification

The specific ligands in natural product extracts could be identified from a multi-target system by ultrafiltration-high performance liquid chromatography using competitive probes.

scholarly journals Extraction from Moist Snuff with Artificial Saliva of Benzo[a]pyrene and Other Polycyclic Aromatic Hydrocarbons

2019 ◽  
Vol 28 (5) ◽  
pp. 214-223
Author(s):  
Serban C. Moldoveanu ◽  
Jerry W. Marshall ◽  
Thomas H. Poole
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Aromatic Hydrocarbons ◽  
High Performance ◽  
Artificial Saliva ◽  
Solid Material ◽  
Chromatography Method ◽  
Freeze Dried ◽  
Moist Snuff ◽  
Polycyclic Aromatic

SummaryThe present study evaluated in vitro extractability of various polycyclic aromatic hydrocarbons (PAHs) from moist snuff, when the extracting agent was water or artificial saliva. The extraction was performed on nine brands of moist snuff samples that are commercially available and were purchased from the market in January 2018. The moist snuff brands were selected to represent brands with different tobacco cut size descriptors and flavors. For the measurement of PAHs, two different analytical methods were used, an HPLC (High Performance Liquid Chromatography) method for measuring only benzo[a]pyrene (BaP) and a GC/MS/MS (Gas Chromatography Tandem Mass Spectrometry) method for measuring 21 PAHs (including BaP). These methods were modifications of preexistent methods reported in the literature. The results for BaP indicated that by extracting 500 mg of freeze-dried moist snuff with 6 portions of 20 mL water (120 mL), or with 4 portions of 20 mL artificial saliva, followed by two portions of 20 mL water, the BaP remains close to 100% in the solid material and it is not detected in the extracting solution. PAHs with a molecular weight similar or heavier than BaP also showed no extractability. Lighter PAHs such as fluorene, phenanthrene, anthracene, and 5-methylanthracene showed a relatively good extractability. An intermediate group including fluoranthene, pyrene, and benz[a]anthracene showed some extractability in the conditions of this in vitro experiment. This study is not a substitute for clinical studies regarding PAH uptake in human users of moist snuff. However, the results indicate very limited bioavailability of BaP and heavier PAHs from moist snuff. Higher, but variable bioavailability was indicated for lighter PAHs. Important implications of these findings are that: 1) measurably different BaP content of two moist snuff products is unlikely to result in any meaningfully different consumer exposure to BaP; and 2) biomarkers for one PAH cannot necessarily be used as a reliable indicator of exposure to another PAH, particularly if the molecular weights of the precursor PAHs differ since their bioavailabilities can be very different. [Beitr. Tabakforsch. Int. 28 (2019) 214–223]

MECHANISM OF ACTION OF GLUCOCORTICOIDS IN INDUCTION OF OVINE PARTURITION: EFFECT ON PLACENTAL STEROID METABOLISM

1975 ◽  
Vol 66 (1) ◽  
pp. 61-70 ◽  
Author(s):  
ANNE B. M. ANDERSON ◽  
A. P. F. FLINT ◽  
A. C. TURNBULL
Keyword(s):  
Specific Activity ◽  
Placental Tissue ◽  
Maternal Plasma ◽  
Steroid Metabolism ◽  
Dexamethasone Treatment ◽  
Chain Cleavage ◽  
Before And After ◽  
Cleavage Enzyme ◽  
Spontaneous Onset

SUMMARY Maternal plasma progesterone levels in sheep may fall dramatically during the last few days of gestation and following the administration of glucocorticoids to the foetus. To investigate the mechanism of the fall, metabolism of [3H]pregnenolone and/or [3H]progesterone in vitro by ovine placental tissue was studied in five ewes before and after intra-foetal administration of dexamethasone in a dosage sufficient to induce parturition, and in one ewe after the spontaneous onset of labour at 143 days of gestation. Manual separation of maternal and foetal placental tissues showed that, in 11 out of 12 cases, the foetal and not the maternal placenta produced progesterone from pregnenolone in vitro. Total activities of cholesterol side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase in the foetal placenta were not influenced by intra-foetal dexamethasone. Before administration of dexamethasone, homogenates of foetal placenta converted [3H]progesterone to 20α-hydroxy [3H]pregn-4-en3-one in the presence of NADPH. Within 12 h of administration of dexamethasone, and after the natural onset of labour at 143 days, large amounts of 17α,20α-dihydroxy[3H]pregn4-en-3-one were formed from [3H]progesterone. Intra-foetal dexamethasone treatment also induced the formation of 17α,20α-dihydroxy[3H]pregn-4-en-3-one by minced foetal placental tissue incubated with [3H]pregnenolone. This change in steroid metabolism did not occur in foetal placental tissue from a sham-operated animal receiving no dexamethasone. Assay of progesterone in foetal placentae showed that the increased formation of 17α,20αdihydroxypregn-4-en-3-one was unlikely to be caused by a change in the specific activity of added 3H-labelled precursor, although the production of 17α,20α-dihydroxypregn-4-en3-one in vitro increased at a time when both foetal placental and utero-ovarian venous levels of progesterone were decreasing in response to dexamethasone treatment. These observations indicate that intra-foetal dexamethasone treatment induces a placental 17α-hydroxylase enzyme, which is also present in foetal placental tissue after the spontaneous onset of labour at term.

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