The Effect of Selenium on CYP450 Isoform Activity and Expression in Pigs

Jiang, Zhihui; Gu, Lingbiao; Liang, Xiuli; Cao, Baorui; Zhang, Jingmiao; Guo, Xin

doi:10.1007/s12011-019-01945-7

Cited by 11 publications

(4 citation statements)

References 36 publications

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“…The CYP1A2, CYP2A19, CYP2E1, CYP3A29, CYP4A24, MRP2, and GSTA1 genes were chosen for this study because they encode proteins with enzymatic activity or transporter function that are involved in Phase I and Phase II of biotransformation and detoxification of xenobiotics to form electrophilic reactive metabolites [64].…”

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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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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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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“…This was conducted by BGI Americas (Cambridge, MA, United States) as described ( Jiang et al, 2019 ; Zhou et al, 2020 ) on three biological replicates per group, each representing a pooled sample of one retina plus RPE from five to six 9-month old 5XFAD male mice after the 2nd treatment ( Petrov et al, 2019a ). Briefly, total RNA was extracted by Trizol (Invitrogen, #15596026, Waltham, MA, United States) according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

Low-Dose Anti-HIV Drug Efavirenz Mitigates Retinal Vascular Lesions in a Mouse Model of Alzheimer’s Disease

et al. 2022

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A small dose of the anti-HIV drug efavirenz (EFV) was previously discovered to activate CYP46A1, a cholesterol-eliminating enzyme in the brain, and mitigate some of the manifestation of Alzheimer’s disease in 5XFAD mice. Herein, we investigated the retina of these animals, which were found to have genetically determined retinal vascular lesions associated with deposits within the retinal pigment epithelium and subretinal space. We established that EFV treatment activated CYP46A1 in the retina, enhanced retinal cholesterol turnover, and diminished the lesion frequency >5-fold. In addition, the treatment mitigated fluorescein leakage from the aberrant blood vessels, deposit size, activation of retinal macrophages/microglia, and focal accumulations of amyloid β plaques, unesterified cholesterol, and Oil Red O-positive lipids. Studies of retinal transcriptomics and proteomics identified biological processes enriched with differentially expressed genes and proteins. We discuss the mechanisms of the beneficial EFV effects on the retinal phenotype of 5XFAD mice. As EFV is an FDA-approved drug, and we already tested the safety of small-dose EFV in patients with Alzheimer’s disease, our data support further clinical investigation of this drug in subjects with retinal vascular lesions or neovascular age-related macular degeneration.

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“…Prevalence of MI was lower in patients with higher selenium levels [51], particularly in females, in whom also stronger associations were suggested with hypertension and diabetes than males for incident MI [52]. Low selenium levels are suggested to affect cytochrome P450 enzymes [53,54], which are important for the pharmacokinetics of several cardiovascular drugs [55,56], and can consequently affect or reduce their efficacy. Since obesity, hypertension and diabetes mellitus are typical clinical demographics of patients with HF and preserved ejection fraction (HFpEF) [57], our findings may hint towards a HFpEF-like phenotype [1,58].…”

Section: Combined Overweight and Micronutrient Undernourishment: Doub...mentioning

confidence: 99%

Sexual dimorphism in selenium deficiency is associated with metabolic syndrome and prevalence of heart disease

Weening

Al‐Mubarak

Dokter

et al. 2023

Cardiovasc Diabetol

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Background Serum selenium levels have been associated with the incidence of heart failure (HF) and signs of the metabolic syndrome. In addition, notable differences have been reported between males and females in food intake and micronutrient metabolism, possibly explaining different health outcomes. Objective Our objective was to elucidate sex-specific, cross-sectional phenotypic differences in the association of serum selenium concentrations with parameters of metabolic syndrome and HF. Methods We investigated data from individuals from a community-based cohort (PREVEND; N = 4288) and heart failure cohort (BIOSTAT-CHF; N = 1994). In both populations, cross-sectional analyses were performed for potential interaction (p < 0.1) between sex and serum selenium with overlapping signs and clinical parameters of the metabolic syndrome and HF. Results Baseline selenium levels of the total cohort were similar between PREVEND (85.7 μg/L) and BIOSTAT-CHF (89.1 μg/L). Females with lower selenium levels had a higher BMI and increased prevalence of diabetes than females with higher selenium, in both PREVEND (pinteraction < 0.001; pinteraction = 0.040, resp.) and BIOSTAT-CHF (pinteraction = 0.021; pinteraction = 0.024, resp.), while opposite associations were observed for males. Additionally, in females, but not in males, lower selenium was associated with a higher prevalence of myocardial infarction (MI) in PREVEND (pinteraction = 0.021) and BIOSTAT-CHF (pinteraction = 0.084). Conclusion Lower selenium was associated with a higher BMI and increased prevalence of diabetes in females, opposite to males, and was also associated with more MI in females. Interventional studies are needed to validate this observation.

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The Effect of Selenium on CYP450 Isoform Activity and Expression in Pigs

Cited by 11 publications

References 36 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

Low-Dose Anti-HIV Drug Efavirenz Mitigates Retinal Vascular Lesions in a Mouse Model of Alzheimer’s Disease

Sexual dimorphism in selenium deficiency is associated with metabolic syndrome and prevalence of heart disease

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