Low-Dose Trichloroethylene Alters Cytochrome P450-2C Subfamily Expression in the Developing Chick Heart

Makwana, Om; Ahles, Lauren; Lencinas, Alejandro; Selmin, Ornella I.; Runyan, Raymond B.

doi:10.1007/s12012-012-9180-0

Cited by 21 publications

(20 citation statements)

References 35 publications

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“…If EETs really play a role in development, alterations in the strict spatio-temporal pattern of the expression of CYP epoxygenases and/or sEH during human prenatal development by xenobiotics could have adverse consequences for the developing organism. Recently, it has been described that changes in the expression of CYP2C induced by trichlorethylene cause improper development of the chicken heart [Makwana et al, 2013].…”

Section: Discussionmentioning

confidence: 99%

Soluble Epoxide Hydrolase as a Potential Key Factor for Human Prenatal Development

Čížková¹,

Rajdová²,

Ehrmann³

2016

Cells Tissues Organs

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Soluble epoxide hydrolase (sEH) converts highly active epoxyeicosatrienoic acids (EETs) generated by cytochrome P450 (CYP) epoxygenases from arachidonic acid to less active dihydroxyeicosatrienoic acids. Because of the role of EETs in processes potentially relevant to the development of organisms, EETs could be suggested as potential morphogens. Unfortunately, only little is known about sEH expression during human intrauterine development (IUD). We investigated the spatio-temporal expression pattern of sEH in human embryonic/foetal intestines, liver and kidney from the 6th to the 20th week of IUD by two-step immunohistochemistry. sEH was expressed during the whole tested period of prenatal development and its level of expression remained more or less the same during the estimated period of IUD. Distribution of CYP epoxygenases and sEH in the intestinal epithelium and the nephrogenic zone of the kidney suggests an influence of EETs on cell proliferation and differentiation and, consequently, on the development of intestines and kidney. Thus, alterations in the strict spatio-temporal pattern of expression of CYP epoxygenases and/or sEH during human prenatal development by xenobiotics could have a harmful impact for developing organisms.

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Section: Discussionmentioning

confidence: 99%

Soluble Epoxide Hydrolase as a Potential Key Factor for Human Prenatal Development

Čížková¹,

Rajdová²,

Ehrmann³

2016

Cells Tissues Organs

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“…Evidence for chemical disruption of these processes is available for trichloroethylene (TCE), estrogens, dioxin, cigarette smoke, other volatiles such as alcohol and metals among other compounds. Amongst these chemicals, TCE, an organic solvent and common environmental contaminant, used primarily as an industrial degreasing agent as n-hexane, has been well studied on the association between exposure and congenital heart malformations [20,37,38]. Data has demonstrated that the earliest embryonic expression of phase I detoxification enzymes is in the developing heart, and expression of these CYPs is relevant to the susceptibility of the developing heart to environmental teratogens [37].…”

Section: Discussionmentioning

confidence: 99%

“…Amongst these chemicals, TCE, an organic solvent and common environmental contaminant, used primarily as an industrial degreasing agent as n-hexane, has been well studied on the association between exposure and congenital heart malformations [20,37,38]. Data has demonstrated that the earliest embryonic expression of phase I detoxification enzymes is in the developing heart, and expression of these CYPs is relevant to the susceptibility of the developing heart to environmental teratogens [37]. Any perturbation of cardiac function contributes to the etiology of congenital heart defects in TCEexposed embryos, while the ventricular septal defect induced by TCE may be secondary to functional impairments that alter cardiac hemodynamics and subsequent ventricular foramen closure, which is consistent with recent demonstrations that TCE impairs calcium handling in cardiomyocytes [39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Effects of 2,5-hexanedione on angiogenesis and vasculogenesis in chick embryos

Cheng

Luo

Wang

et al. 2015

Reproductive Toxicology

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“…However, CYP epoxygenases are up-regulated by PPARa in human beings, and their spatio-temporal expression pattern in human embryonic/ foetal tissues has been described recently [16]. It has also been noted that changes in the expression of CYP2C induced by the environmental teratogen trichloroethylene lead to improper development of the chicken heart [17]. Trichloroethylene is a known PPARa ligand and whether this effect is mediated by this receptor warrants further investigation.…”

Section: Resultsmentioning

confidence: 99%

Spatio‐Temporal Expression of Peroxisome Proliferator‐Activated Receptor α During Human Prenatal Development

Čížková

Rajdová

Ehrmann

2014

Basic Clin Pharma Tox

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Peroxisome proliferator-activated receptor a (PPARa) is a ligand-dependent transcription factor which is activated by various endogenous as well as exogenous compounds. It is involved in the regulation of a variety of biological processes, such as nutrient metabolism, energy homoeostasis, immunological response and xenobiotic metabolism. Little is known about its expression during human prenatal development. We examined the spatio-temporal expression pattern of PPARa in human embryonic/foetal intestines, liver and kidney from the 5th to 20th week of prenatal life by indirect two-step immunohistochemistry. PPARa expression can already be detected in the early stages of prenatal development; as early as the 7th week of intrauterine development (IUD) in the intestines, 5th week of IUD in the liver and 6th week of IUD in the kidney. We found agedependent changes in the PPARa expression pattern in the intestines and kidney. These events occur approximately at the commencement of function of these organs. In the intestines, we detected an obvious change of the PPARa expression pattern along the crypt-villous axis in the 11th week of IUD. In the kidney, the most apparent change was increased expression of PPARa in glomeruli in the 12th week of IUD. Moreover, in the liver, we detected a strong positivity in part of the developing blood elements. Information about the spatio-temporal expression pattern of PPARa could be the first step in evaluating the potential harmful impact of a wide range of environmental or pharmaceutical compounds which serve as PPARa ligands on the developing human organism.Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that belong to the nuclear receptor superfamily. PPARs consist of three members: peroxisome proliferator-activated receptor a (PPARa), PPARb/d and PPARc. The receptors are encoded by different genes and activated by different compounds. PPARa is well known as a regulator of nutrient metabolism and energy homoeostasis. Moreover, it is involved in the regulation of inflammation and immune response as well as xenobiotic metabolism [1]. After ligand binding, PPARs bind to the peroxisome proliferator response element in the promoter region of target genes as a heterodimer with retinoid X receptor (RXR). Beside ligands, the receptors interact with a huge number of co-activators and co-repressors. Furthermore, their transcriptional activity can also be modulated by cross-talk between phosphorylation and dephosporylation. The effect of these modifications depends on cellular context, receptor type and residue metabolized [2].PPARa is activated by a wide range of both endogenous and exogenous ligands, such as dietary fatty acids, eicosanoids, hypolipidaemic drugs, phthalates, pesticides, etc. The receptor is highly expressed in tissues with active fatty acid metabolism, such as the liver, heart muscle, intestine and kidney. Inappropriate activation of the receptor during prenatal development by xenobiotics can alter gene expression. ...

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Low-Dose Trichloroethylene Alters Cytochrome P450-2C Subfamily Expression in the Developing Chick Heart

Cited by 21 publications

References 35 publications

Soluble Epoxide Hydrolase as a Potential Key Factor for Human Prenatal Development

Soluble Epoxide Hydrolase as a Potential Key Factor for Human Prenatal Development

Effects of 2,5-hexanedione on angiogenesis and vasculogenesis in chick embryos

Spatio‐Temporal Expression of Peroxisome Proliferator‐Activated Receptor α During Human Prenatal Development

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