Porcine cytochrome 2A19 and 2E1

Burkina, Viktoriia; Rasmussen, Martin Krøyer; Oliinychenko, Yelyzaveta; Zamaratskaia, Galia

doi:10.1111/bcpt.13121

Cited by 14 publications

(10 citation statements)

References 74 publications

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“…CYP2A19 transcription is controlled by the CAR transcription factor [ 78 ]. Its human orthologue, CYP2A6 is controlled by CAR, PXR, glucocorticoid receptor (GR), estrogen receptor

HNF 4

, and PGC-1 α [ 79 ]. Also, the constitutive hepatic expression of CYP2A6 in mice is governed by an interplay between HNF 4

, CCAAT-box/enhancer binding protein (C/EBP

, C/EBP

and octamer transcription factor-1 (Oct-1) [ 80 ].…”

Section: Discussionmentioning

confidence: 99%

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The Effectiveness of Dietary Byproduct Antioxidants on Induced CYP Genes Expression and Histological Alteration in Piglets Liver and Kidney Fed with Aflatoxin B1 and Ochratoxin A

Popescu

Bulgaru

Untea

et al. 2021

Toxins

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The purpose of this study was to investigate the potential of a byproduct mixture derived from grapeseed and sea buckthorn oil industry to mitigate the harmful damage produced by ochratoxin A and aflatoxin B1 at hepatic and renal level in piglets after weaning. Forty cross-bred TOPIGS-40 hybrid piglets after weaning were assigned to three experimental groups (E1, E2, E3) and one control group (C), and fed with experimental diets for 30 days. The basal diet was served as a control and contained normal compound feed for starter piglets without mycotoxins. The experimental groups were fed as follows: E1—basal diet plus a mixture (1:1) of two byproducts (grapeseed and sea buckthorn meal); E2—the basal diet experimentally contaminated with mycotoxins (479 ppb OTA and 62ppb AFB1); and E3—basal diet containing 5% of the mixture (1:1) of grapeseed and sea buckthorn meal and contaminated with the mix of OTA and AFB1. After 4 weeks, the animals were slaughtered, and tissue samples were taken from liver and kidney in order to perform gene expression and histological analysis. The gene expression analysis showed that when weaned piglets were fed with contaminated diet, the expression of most analyzed genes was downregulated. Among the CYP450 family, CYP1A2 was the gene with the highest downregulation. According to these results, in liver, we found that mycotoxins induced histomorphological alterations in liver and kidney and had an effect on the expression level of CYP1A2, CYP2A19, CYP2E1, and CYP3A29, but we did not detect important changes in the expression level of CY4A24, MRP2 and GSTA1 genes.

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“…CYP2A19 transcription is controlled by the CAR transcription factor [ 78 ]. Its human orthologue, CYP2A6 is controlled by CAR, PXR, glucocorticoid receptor (GR), estrogen receptor

HNF 4

, and PGC-1 α [ 79 ]. Also, the constitutive hepatic expression of CYP2A6 in mice is governed by an interplay between HNF 4

, CCAAT-box/enhancer binding protein (C/EBP

, C/EBP

and octamer transcription factor-1 (Oct-1) [ 80 ].…”

Section: Discussionmentioning

confidence: 99%

“…In pig kidney, the expression of CYP2A19 is lower compared to that found in liver [ 79 ]. Probably due to this lower expression, animal exposure to the mixture of grapeseed and sea buckthorn meal generated an upregulation of Nrf-2 induced CYP2A19 gene expression due to the luteolin [ 85 ] and ferulic acid [ 86 ] content.…”

Section: Discussionmentioning

confidence: 99%

The Effectiveness of Dietary Byproduct Antioxidants on Induced CYP Genes Expression and Histological Alteration in Piglets Liver and Kidney Fed with Aflatoxin B1 and Ochratoxin A

Popescu

Bulgaru

Untea

et al. 2021

Toxins

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“…diet, (un)controlled housing conditions etc. ), and to breed-related genetic variations (Burkina et al, 2019). In humans, however, the CYP2E1 ontogeny pattern shows a gradual postnatal increase, specifically from the first month of life until 1 year of age (Vieira et al, 1996;Johnsrud et al, 2003).…”

Section: Cyp Protein Abundance Ontogeny Profilesmentioning

confidence: 99%

Hepatic Cytochrome P450 Abundance and Activity in the Developing and Adult Göttingen Minipig: Pivotal Data for PBPK Modeling

et al. 2021

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The Göttingen Minipig is gaining ground as nonrodent species in safety testing of drugs for pediatric indications. Due to developmental changes in pharmacokinetics and pharmacodynamics, physiologically based pharmacokinetic (PBPK) models are built to better predict drug exposure in children and to aid species selection for nonclinical safety studies. These PBPK models require high quality physiological and ADME data such as protein abundance of drug metabolizing enzymes. These data are available for man and rat, but scarce for the Göttingen Minipig. The aim of this study was to assess hepatic cytochrome P450 (CYP) protein abundance in the developing Göttingen Minipig by using mass spectrometry. In addition, sex-related differences in CYP protein abundance and correlation of CYP enzyme activity with CYP protein abundance were assessed. The following age groups were included: gestational day (GD) 84–86 (n = 8), GD 108 (n = 6), postnatal day (PND) 1 (n = 8), PND 3 (n = 8), PND 7 (n = 8), PND 28 (n = 8) and adult (n = 8). Liver microsomes were extracted and protein abundance was compared to that in adult animals. Next, the CYP protein abundance was correlated to CYP enzyme activity in the same biological samples. In general, CYP protein abundance gradually increased during development. However, we observed a stable protein expression over time for CYP4A24 and CYP20A1 and for CYP51A1, a high protein expression during the fetal stages was followed by a decrease during the first month of life and an increase toward adulthood. Sex-related differences were observed for CYP4V2_2a and CYP20A1 at PND 1 with highest expression in females for both isoforms. In the adult samples, sex-related differences were detected for CYP1A1, CYP1A2, CYP2A19, CYP2E1_2, CYP3A22, CYP4V2_2a and CYP4V2_2b with higher values in female compared to male Göttingen Minipigs. The correlation analysis between CYP protein abundance and CYP enzyme activity showed that CYP3A22 protein abundance correlated clearly with the metabolism of midazolam at PND 7. These data are remarkably comparable to human data and provide a valuable step forward in the construction of a neonatal and juvenile Göttingen Minipig PBPK model.

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“…In the present study, these three CYPs were significantly up-regulated in SNT and LZT livers, suggesting that high-altitude environments are more prone to toxin production, which in turn induces toxicological responses in animal livers. Some studies have reported that CYP2E1 is most abundant in adult pig liver tissue and is able to metabolize many drugs and environmental toxins, playing a key role in the detoxification chain [ 26 , 27 ]. UGTs are a phase-II-specific family of enzymes that are capable of coupling and accelerating the metabolism of drugs and toxins.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Proteomic Analysis of Tibetan Pig Livers at Different Altitudes

Chang

Yang

et al. 2023

Molecules

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In this study, the differences in protein profiles between the livers of Shannan Tibetan pigs (SNT), Linzhi Tibetan pigs (LZT) and Jiuzhaigou Tibetan pigs (JZT) were comparatively analyzed by tandem mass spectrometry-labeling quantitative proteomics. A total of 6804 proteins were identified: 6471 were quantified and 1095 were screened as differentially expressed proteins (DEPs). Bioinformatics analysis results show that, compared with JZT livers, up-regulated DEPs in SNT and LZT livers mainly promoted hepatic detoxification through steroid hormone biosynthesis and participated in lipid metabolism to maintain body energy homeostasis, immune response and immune regulation, while down-regulated DEPs were mainly involved in lipid metabolism and immune regulation. Three proteases closely related to hepatic fatty acid oxidation were down-regulated in enzymatic activity, indicating higher levels of lipid oxidation in SNT and LZT livers than in JZT livers. Down-regulation of the expression of ten immunoglobulins suggests that JZT are more susceptible to autoimmune diseases. It is highly likely that these differences in lipid metabolism and immune-related proteins are in response to the ecological environment at different altitudes, and the findings contribute to the understanding of the potential molecular link between Tibetan pig livers and the environment.

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Porcine cytochrome 2A19 and 2E1

Cited by 14 publications

References 74 publications

The Effectiveness of Dietary Byproduct Antioxidants on Induced CYP Genes Expression and Histological Alteration in Piglets Liver and Kidney Fed with Aflatoxin B1 and Ochratoxin A

The Effectiveness of Dietary Byproduct Antioxidants on Induced CYP Genes Expression and Histological Alteration in Piglets Liver and Kidney Fed with Aflatoxin B1 and Ochratoxin A

Hepatic Cytochrome P450 Abundance and Activity in the Developing and Adult Göttingen Minipig: Pivotal Data for PBPK Modeling

Quantitative Proteomic Analysis of Tibetan Pig Livers at Different Altitudes

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