ArticleEnvironmental health perspectives2020
Evaluating the Role of the Steroid and Xenobiotic Receptor (SXR/PXR) in PCB-153 Metabolism and Protection against Associated Adverse Effects during Perinatal and Chronic Exposure in Mice.
Article in Environmental health perspectives, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Review
- Pregnane X receptor (NR1I2) deficiency in mice reveals context-dependent regulation of inflammatory homeostasis.Frontiers in immunology · 2026Review
- Enantiomeric Fractions Reveal Differences in the Atropselective Disposition of 2,2',3,5',6-Pentachlorobiphenyl (PCB 95) in Wildtype,Chemical research in toxicology · 2023Article
- Probing the Role of CYP2 Enzymes in the Atropselective Metabolism of Polychlorinated Biphenyls Using Liver Microsomes from Transgenic Mouse Models.Chemical research in toxicology · 2022Article
- Machine Learning-Assisted Identification and Quantification of Hydroxylated Metabolites of Polychlorinated Biphenyls in Animal Samples.Environmental science & technology · 2022Article
- Pregnane X Receptor and the Gut-Liver Axis: A Recent Update.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Aroclor 1254 induced inhibitory effects on osteoblast differentiation in murine MC3T3-E1 cells through oxidative stress.Frontiers in endocrinology · 2022Article
- Jekyll and Hyde: nuclear receptors ignite and extinguish hepatic oxidative milieu.Trends in endocrinology and metabolism: TEM · 2021Review
- The Potential Relationship Between Environmental Endocrine Disruptor Exposure and the Development of Endometriosis and Adenomyosis.Frontiers in physiology · 2021Review
- Article
- Control of Adipose Cell Browning and Its Therapeutic Potential.Metabolites · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPolychlorinated biphenyls (PCBs) are environmental toxicants; PCB exposure has been associated with adverse effects on wildlife and humans. However, the mechanisms underlying these adverse effects are not fully understood. The steroid and xenobiotic receptor [SXR; also known as the pregnane X receptor (PXR) and formally known as NR1I2] is a nuclear hormone receptor that regulates inducible metabolism of drugs and xenobiotics and is activated or inhibited by various PCB congeners.
objectivesThe aim of this study was to investigate the effects of exposure to PCB-153, the most prevalent PCB congener in human tissues, on SXR knockout mice (SXRKO) and to elucidate the role of SXR in PCB-153 metabolism and promotion of its harmful effects.
methodsWild-type (WT) and SXRKO mice were chronically or perinatally exposed to a low dose (
resultsSXRKO mice perinatally exposed to PCB-153 displayed elevated oxidative stress, symptoms of hemolytic anemia, and premature death. Transcriptomal analysis revealed that expression of genes involved in metabolic processes was altered in SXRKO mice. Elevated levels of the PCB-153 metabolite, 3-OH-PCB-153, were found in exposed SXRKO mice compared to exposed WT mice. Blood hemoglobin (HGB) levels were lower throughout the lifespan, and the occurrence of intestinal tumors was larger in SXRKO mice chronically exposed to PCB-153 compared to vehicle and WT controls. DISCUSSION: Our results suggest that altered metabolism induced by SXR loss of function resulted in the accumulation of hydroxylated metabolites upon exposure to PCB-153, leading to oxidative stress, hemolytic anemia, and tumor development in a mouse model. These results support a major role for SXR/PXR in protection against xenobiotic-induced oxidative stress by maintaining proper metabolism in response to PCB-153 exposure. This role of SXR could be generally applicable to other environmental toxicants as well as pharmaceutical drugs. https://doi.org/10.1289/EHP6262.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.