Porcine cytochrome P450 3A: current status on expression and regulation

Rasmussen, Martin Krøyer

doi:10.1007/s00204-020-02710-9

Cited by 9 publications

(4 citation statements)

References 133 publications

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“…In agreement with previous results, treatment with rifampicin increased the mRNA and protein expression of the human CYP3A4 and porcine CYP3A’s ( Rasmussen, 2017 , Rasmussen, 2020 , Rasmussen et al, 2017 ). The same pattern was observed in response to phenobarbital but not to CITCO which is a ligand for CAR.…”

Section: Discussionsupporting

confidence: 93%

Primary hepatocytes isolated from human and porcine donors display similar patterns of cytochrome p450 expression following exposure to prototypical activators of AhR, CAR and PXR

Gerbal‐Chaloin

Briolotti

Daujat-Chavanieu

et al. 2021

Current Research in Toxicology

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Section: Discussionsupporting

confidence: 93%

Primary hepatocytes isolated from human and porcine donors display similar patterns of cytochrome p450 expression following exposure to prototypical activators of AhR, CAR and PXR

Gerbal‐Chaloin

Briolotti

Daujat-Chavanieu

et al. 2021

Current Research in Toxicology

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“…In contrast, it has been found that in the presence of OTA and AFB1 in liver ( Figure 3, group E2), the CYP3A29 expression level is decreased compared to the control level, perhaps due to activation of the AhR [98]. These data differ from those of Zepnik et al [99], who reported an increase of OTA hydrolysis by microsomal enzymes from rat liver, specifically for P450 3A1/2 and 3A4, suggesting that this gene expression is modulated in a species-dependent manner.…”

Section: Discussionmentioning

confidence: 81%

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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“…The CYP3A subfamily, represented by four isozymes (i.e., 3A22, 3A29, 3A39 and 3A46), is constitutively expressed in porcine liver (Rasmussen, 2020); all members have been identi ed at the mRNA and protein levels. Commonly used drugs in swine production, such as macrolide antibiotics and tiamulin, are known substrates of this subfamily (Nebbia, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Commonly used drugs in swine production, such as macrolide antibiotics and tiamulin, are known substrates of this subfamily (Nebbia, 2001). The degree of CYP3A-dependent metabolism in pig liver has been related to the rate of testosterone 6-β and 16-β hydroxylation, but also by the measurement of BROD activity (Puccinelli et al, 2011;Rasmussen et al, 2020). Reported values for testosterone 6-β hydoxylase activity in pig liver microsomes ranged from 0.45 to 4.45 nmol/min.mg protein (Puccinelli et al, 2011); the metabolic rates obtained in both control and FBZ-treated animals (see Table 1) are in agreement with those previously reported.…”

Section: Discussionmentioning

confidence: 99%

Sustained Treatment With Fenbendazole in Swine: Plasma Availability and Effects on Xenobiotic Metabolizing Enzymes in the Liver

Ichinose

Miró

Larsen

et al. 2022

Preprint

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Fenbendazole (FBZ), a benzymidazole (BZD) anthelmintic drug, is used for in-feed medication in pigs. BZD-containing drugs may induce cytochrome P450 isozymes (CYPs), particularly those members of the CYP1A subfamily. This research aimed to evaluate in vitro the effect of the in vivo sustained administration of FBZ on the catalytic activities of xenobiotic metabolizing enzymes in pig liver. The availability of FBZ and its metabolites in plasma and liver tissue was also assessed. Five Landrace piglets remained untreated (controls), and other six were treated with a pre-mix of FBZ, combined with food, for 9 consecutive days as usually is recommended by practitioners. Blood samples were collected from each treated animal up to day 9 and analyzed by HPLC; both control and treated animals were slaughtered for preparation of liver microsomes. Plasma concentration ratios OFZ/FBZ and FBZSO2/OFZ increased significantly (p<0.05) from the beginning to the end of drug exposure, which may indicate an enhanced conversion of FBZ into its metabolites. FBZ represented 45.8±3.4% of the total anthelmintic molecules in liver tissue. Increased CYP1A-dependent 7-ethoxy (24.5-fold, p=0.0032) and 7-methoxyresorufin (17.2-fold, p=0.0006) O-dealkylase activities was observed in liver microsomes from FBZ-treated animals. The continuous FBZ administration may accelerate its own in vivo hepatic metabolism through the CYP1A pathway, which may have a negative impact on its clinical efficacy. CYP1A induction in pig liver may also affect the biotransformation of other xenobiotics such as aflatoxin B1 present in certain pig foodstuffs.

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Porcine cytochrome P450 3A: current status on expression and regulation

Cited by 9 publications

References 133 publications

Primary hepatocytes isolated from human and porcine donors display similar patterns of cytochrome p450 expression following exposure to prototypical activators of AhR, CAR and PXR

Primary hepatocytes isolated from human and porcine donors display similar patterns of cytochrome p450 expression following exposure to prototypical activators of AhR, CAR and PXR

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

Sustained Treatment With Fenbendazole in Swine: Plasma Availability and Effects on Xenobiotic Metabolizing Enzymes in the Liver

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