Clinically Relevant Concentrations Of Di (2-ethylhexyl) Phthalate (dehp) Uncouple Cardiac Syncytium

Gillum, Nikki; Karabekian, Zara; Sarvazyan, Narine

doi:10.1016/j.bpj.2008.12.3297

Cited by 16 publications

(24 citation statements)

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“…Some studies have shown that exposure to PA among 1-day-old rats can destroy the essential components of gap junctions in cardiac cells such as connexin-43, as well as the genes associated with cardiac arrhythmogenicity [19]. It has also been reported that exposure to PA can change the cardiomyocyte metabolic profile and can consequently make heart prone to ischemia and ventricular dysfunctions.…”

Section: Introductionmentioning

confidence: 97%

Prenatal Exposure to Phthalic Acid Induces Increased Blood Pressure, Oxidative Stress, and Markers of Endothelial Dysfunction in Rat Offspring

et al. 2015

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Previous studies have reported the harmful effects of exposure to phthalic acid (PA) on heart. No studies have reported the effects of prenatal PA exposure on the structure or function of heart. The current study aimed to investigate the effects of prenatal PA exposure on the markers of oxidative stress and cardiac structure in rats' offspring. Twenty-four pregnant rats were randomly categorized into three groups of control, exposed to 2.5 and 5 % PA. The morphometric properties of coronary arteries, markers of oxidative stress, and NOS activity were measured in offspring rats. By a dose-dependent manner, the body weight (BW), heart weight (HW), and HW/BW of the intervention groups were reduced and their heart rate and blood pressure were conversely increased compared to the control group. Also, the wall thickness, cross-sectional area of the aorta and septal branch of the descending left coronary artery were significantly increased in the intervention group. In addition, PA significantly increased the level of malondialdehyde and decreased the level of superoxide dismutase and glutathione peroxidase, compared to the control group. This study revealed that prenatal exposure of rats to PA causes vascular dysfunction, increasing oxidative stress, and reduction in cardiac nitric oxide synthetase activity among offspring rats.

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Section: Introductionmentioning

confidence: 97%

Prenatal Exposure to Phthalic Acid Induces Increased Blood Pressure, Oxidative Stress, and Markers of Endothelial Dysfunction in Rat Offspring

et al. 2015

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“…An interesting report by Li et al (2011) showed that the concentrations of phthalate esters, including DEHP, in semen or serum samples were positively associated with circulating prolactin levels in adult men. DEHP was also recently described to impair the electrical and mechanical behavior of cardiac cell network (Gillum et al 2009). However, the underlying mechanisms through which phthalate esters interact with membrane ion channels remain largely unexplored.…”

Section: Introductionmentioning

confidence: 98%

The inhibition by di(2-ethylhexyl)-phthalate of erg-mediated K+ current in pituitary tumor (GH3) cells

Yang

Yeh

et al. 2012

Arch Toxicol

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DEHP (bis(2-ethylhexyl)-phthalate) known to be an endocrine-disrupting chemical is a widely used phthalate. Little information regarding the effects of phthalate esters on ion currents is available. In this study, the effects of DEHP and other phthalate esters (DBEP: di(2-butoxyethyl)-phthalate and DMGP: di(2-methylglycol)-phthalate) on ion currents were investigated in pituitary GH₃ cells. Hyperpolarization-elicited K⁺ currents in GH3 cells bathed in high-K⁺, Ca²⁺-free solution were examined to evaluate the effects of DEHP, DBEP, and DMGP on the ether-a`-go-go-related-gene (erg) K⁺ current (IK(erg)). Addition of DEHP to GH₃ cells suppressed the amplitude of IK(erg) in a concentration-dependent manner with an IC₅₀ value of 16.3 μM. With a two-pulse protocol, addition of DEHP shifted the activation curve of IK(erg) to a depolarized potential by approximately 10 mV with no change in the rate of IK(erg) deactivation. This compound did not have any effects on delayed rectifier K⁺ current in GH₃ cells, while 4-aminopyridine-3-methanol (100 μM) suppressed this current significantly. DBEP (30 μM) had little or no effect on IK(erg), while DMGP (30 μM) slightly reduced it. In inside-out configuration, DEHP (30 μM) applied to the bath slightly reduced the activity of large-conductance Ca²⁺-activated K⁺ channels. DEHP (30 μM) increased the frequency of spontaneous action potentials (APs); however, this compound at the same concentration had no effect on AP firing in KCNH2 siRNA-transfected GH₃ cells. The effects described herein can contribute to their actions on functional activity of endocrine or neuroendocrine cells if similar results are found in vivo.

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“…These doses are approximately equivalent to 0.492-49.2 lM, which encompass the doses ranging from 0.2 to 20 lg/ ml. The concentrations of DEHP and MEHP selected in these experiments have also been determined to be clinically relevant [20,52,[57][58][59]. Importantly, plasma concentrations of DEHP and MEHP in healthy women have been reported to be 0.18 lg/ml and 0.58 lg/ml, respectively, and peritoneal fluid concentrations of DEHP and MEHP in these women were reported to be 0.46 lg/ml and 0.37 lg/ml, respectively, which encompasses the lower selected concentrations [60].…”

Section: Introductionmentioning

confidence: 99%

Mono(2-Ethylhexyl) Phthalate Accelerates Early Folliculogenesis and Inhibits Steroidogenesis in Cultured Mouse Whole Ovaries and Antral Follicles1

Hannon

Brannick

Wang

et al. 2015

Biology of Reproduction

109

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Humans are ubiquitously exposed to di(2-ethylhexyl) phthalate (DEHP), which is an environmental toxicant present in common consumer products. DEHP potentially targets the ovary through its metabolite mono(2-ethylhexyl) phthalate (MEHP). However, the direct effects of MEHP on ovarian folliculogenesis and steroidogenesis, two processes essential for reproductive and nonreproductive health, are unknown. The present study tested the hypotheses that MEHP directly accelerates early folliculogenesis via overactivation of phosphatidylinositol 3-kinase (PI3K) signaling, a pathway that regulates primordial follicle quiescence and activation, and inhibits the synthesis of steroid hormones by decreasing steroidogenic enzyme levels. Neonatal ovaries from CD-1 mice were cultured for 6 days with vehicle control, DEHP, or MEHP (0.2-20 lg/ml) to assess the direct effects on folliculogenesis and PI3K signaling. Further, antral follicles from adult CD-1 mice were cultured with vehicle control or MEHP (0.1-10 lg/ml) for 24-96 h to establish the temporal effects of MEHP on steroid hormones and steroidogenic enzymes. In the neonatal ovaries, MEHP, but not DEHP, decreased phosphatase and tensin homolog levels and increased phosphorylated protein kinase B levels, leading to a decrease in the percentage of germ cells and an increase in the percentage of primary follicles. In the antral follicles, MEHP decreased the mRNA levels of 17alpha-hydroxylase-17,20-desmolase, 17beta-hydroxysteroid dehydrogenase, and aromatase leading to a decrease in testosterone, estrone, and estradiol levels. Collectively, MEHP mediates the effect of DEHP on accelerated folliculogenesis via overactivating PI3K signaling and inhibits steroidogenesis by decreasing steroidogenic enzyme levels.

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Clinically Relevant Concentrations Of Di (2-ethylhexyl) Phthalate (dehp) Uncouple Cardiac Syncytium

Cited by 16 publications

References 0 publications

Prenatal Exposure to Phthalic Acid Induces Increased Blood Pressure, Oxidative Stress, and Markers of Endothelial Dysfunction in Rat Offspring

Prenatal Exposure to Phthalic Acid Induces Increased Blood Pressure, Oxidative Stress, and Markers of Endothelial Dysfunction in Rat Offspring

The inhibition by di(2-ethylhexyl)-phthalate of erg-mediated K+ current in pituitary tumor (GH3) cells

Mono(2-Ethylhexyl) Phthalate Accelerates Early Folliculogenesis and Inhibits Steroidogenesis in Cultured Mouse Whole Ovaries and Antral Follicles1

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