SynthesisToxicological sciences : an official journal of the Society of Toxicology2010
Characterization of peroxisome proliferator-activated receptor alpha--independent effects of PPARalpha activators in the rodent liver: di-(2-ethylhexyl) phthalate also activates the constitutive-activated receptor.
Synthesis in Toxicological sciences : an official journal of the Society of Toxicology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Systematic transcriptome-wide meta-analysis across endocrine disrupting chemicals reveals shared and unique liver pathways, gene networks, and disease associations.Environment international · 2024Pooled it
- Mitigating the environmental effects of healthcare: the role of the endocrinologist.Nature reviews. Endocrinology · 2025Review
- Quantitative label-free proteomic analysis of mouse ovarian antral follicles following oral exposure to a human-relevant mixture of three phthalates.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- PPARα Induces the Expression of CAR That Works as a Negative Regulator of PPARα Functions in Mouse Livers.International journal of molecular sciences · 2023Article
- Constitutive Androstane Receptor Agonist, TCPOBOP: Maternal Exposure Impairs the Growth and Development of Female Offspring in Mice.International journal of molecular sciences · 2023Article
- Dysregulation of Lipid and Glucose Homeostasis in Hepatocyte-Specific SLC25A34 Knockout Mice.The American journal of pathology · 2022Article
- Perinatal DEHP exposure induces sex- and tissue-specific DNA methylation changes in both juvenile and adult mice.Environmental epigenetics · 2021Article
- Coagulopathy in Malnourished Mice Is Sexually Dimorphic and Regulated by Nutrient-Sensing Nuclear Receptors.Hepatology communications · 2020Article
- Review
- Short- and long-term effects of perinatal phthalate exposures on metabolic pathways in the mouse liver.Environmental epigenetics · 2020Article
- Early microRNA indicators of PPARα pathway activation in the liver.Toxicology reports · 2020Article
- Deficiency or activation of peroxisome proliferator-activated receptor α reduces the tissue concentrations of endogenously synthesized docosahexaenoic acid in C57BL/6J mice.Nutrition research and practice · 2019Article
- Di(2-ethylhexyl) phthalate-induced toxicity and peroxisome proliferator-activated receptor alpha: a review.Environmental health and preventive medicine · 2019Review
- The Increase of ROS Caused by the Interference of DEHP with JNK/p38/p53 Pathway as the Reason for Hepatotoxicity.International journal of environmental research and public health · 2019Article
- Impact of CAR Agonist Ligand TCPOBOP on Mouse Liver Chromatin Accessibility.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Human relevance of rodent liver tumors: Key insights from a Toxicology Forum workshop on nongenotoxic modes of action.Regulatory toxicology and pharmacology : RTP · 2018Review
- The PPARα-dependent rodent liver tumor response is not relevant to humans: addressing misconceptions.Archives of toxicology · 2018Review
- PPARα-independent transcriptional targets of perfluoroalkyl acids revealed by transcript profiling.Toxicology · 2017Article
- Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas.International journal of molecular sciences · 2017Article
- Activation of the Constitutive Androstane Receptor by Monophthalates.Chemical research in toxicology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Peroxisome proliferator chemicals (PPC) are thought to mediate their effects in rodents on hepatocyte growth and liver cancer through the nuclear receptor peroxisome proliferator-activated receptor (PPAR) alpha. Recent studies indicate that the plasticizer di-(2-ethylhexyl) phthalate (DEHP) increased the incidence of liver tumors in PPARalpha-null mice. We hypothesized that some PPC, including DEHP, induce transcriptional changes independent of PPARalpha but dependent on other nuclear receptors, including the constitutive-activated receptor (CAR) that mediates phenobarbital (PB) effects on hepatocyte growth and liver tumor induction. To determine the potential role of CAR in mediating effects of PPC, a meta-analysis was performed on transcript profiles from published studies in which rats and mice were exposed to PPC and compared the profiles to those produced by exposure to PB. Valproic acid, clofibrate, and DEHP in rat liver and DEHP in mouse liver induced genes, including Cyp2b family members that are known to be regulated by CAR. Examination of transcript changes by Affymetrix ST 1.0 arrays and reverse transcription-PCR in the livers of DEHP-treated wild-type, PPARalpha-null, and CAR-null mice demonstrated that (1) most (approximately 94%) of the transcriptional changes induced by DEHP were PPARalpha-dependent, (2) many PPARalpha-independent genes overlapped with those regulated by PB, (3) induction of genes Cyp2b10, Cyp3a11, and metallothionine-1 by DEHP was CAR dependent but PPARalpha-independent, and (4) induction of a number of genes (Cyp8b1, Gstm4, and Gstm7) was independent of both CAR and PPARalpha. Our results indicate that exposure to PPARalpha activators including DEHP leads to activation of multiple nuclear receptors in the rodent liver.
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Registered trials
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.