Effect of Di-(2-ethylhexyl)-phthalate on Sphingolipid Metabolic Enzymes in Rat Liver

Jo, Ji-Yeong; Kim, Tae-Hyung; Jeong, Hye-Young; Lim, Sung-Mee; Kim, Hyung–Sik; Im, Dong‐Soon

doi:10.5487/tr.2011.27.3.185

Cited by 7 publications

(6 citation statements)

References 24 publications

(23 reference statements)

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“…In addition, several correlating sphingolipids such as ceramide, ceramide-1-phosphate, sphingosine, and sphingosine-1-phosphate may serve as signaling molecules that influence obesity, diabetes, metabolic syndrome ( 56 – 58 ), oxidative stress and inflammatory signaling ( 59 ). Previous reports describe the effects of phthalates on sphingolipid metabolism in rat brain linked with hippocampal development ( 60 ) and liver toxicity ( 61 ), but additional research is required to understand their role in maternal-neonate health and obesity.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Markers of Phthalate Exposure in Plasma and Urine of Pregnant Women

Zhou

Ford

Lee

et al. 2018

Front. Public Health

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Phthalates are known endocrine disruptors and found in almost all people with several associated adverse health outcomes reported in humans and animal models. Limited data are available on the relationship between exposure to endocrine disrupting chemicals and the human metabolome. We examined the relationship of metabolomic profiles in plasma and urine of 115 pregnant women with eleven urine phthalate metabolites measured at 26 weeks of gestation to identify potential biomarkers and relevant pathways. Targeted metabolomics was performed by selected reaction monitoring liquid chromatography and triple quadrupole mass spectrometry to measure 415 metabolites in plasma and 151 metabolites in urine samples. We have chosen metabolites with the best defined peaks for more detailed analysis (138 in plasma and 40 in urine). Relationship between urine phthalate metabolites and concurrent metabolomic markers in plasma and urine suggested potential involvement of diverse pathways including lipid, steroid, and nucleic acid metabolism and enhanced inflammatory response. Most of the correlations were positive for both urine and plasma, and further confirmed by regression and PCA analysis. However, after the FDR adjustment for multiple comparisons, only 9 urine associations remained statistically significant (q-values 0.0001–0.0451), including Nicotinamide mononucleotide, Cysteine T2, Cystine, and L-Aspartic acid. Additionally, we found negative associations of maternal pre-pregnancy body mass index (BMI) with more than 20 metabolomic markers related to lipid and amino-acid metabolism and inflammation pathways in plasma (p = 0.01–0.0004), while Mevalonic acid was positively associated (p = 0.009). Nicotinic acid, the only significant metabolite in urine, had a positive association with maternal BMI (p = 0.002). In summary, when evaluated in the context of metabolic pathways, the findings suggest enhanced lipid biogenesis, inflammation and altered nucleic acid metabolism in association with higher phthalate levels. These results provide new insights into the relationship between phthalates, common in most human populations, and metabolomics, a novel approach to exposure and health biomonitoring.

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Section: Discussionmentioning

confidence: 99%

Metabolomic Markers of Phthalate Exposure in Plasma and Urine of Pregnant Women

Zhou

Ford

Lee

et al. 2018

Front. Public Health

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“…Corn oil (Nacalai Tesque, Inc., Kyoto, Japan) was used as the vehicle. The doses for each chemical, which were expected to induce hepatotoxic effects according to the toxicological literature such as IARC Monographs (IARC, 2001;Jo et al, 2011;IARC, 2013), were selected. Test solutions were administered orally by gavage using a flexible catheter joined to a plastic disposable syringe.…”

Section: Chemical Treatmentmentioning

confidence: 99%

The effects on the endocrine system under hepatotoxicity induction by phenobarbital and di(2-ethylhexyl)phthalate in intact juvenile male rats

et al. 2019

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Phenobarbital (PB) and Di (2-ethylhexyl) phthalate (DEHP), an anti-epileptic drug and a plasticizer used in flexible polyvinylchloride formulations, respectively, are well-known typical hepatotoxicants. This study investigated the effects of PB (100 mg/kg/day) or DEHP (500 mg/kg/day) on the endocrine system in intact juvenile/peripubertal male rats exposed for 31 days beginning on postnatal day 23. Slight hormone level changes, histopathological changes in thyroid gland or induction of UDPglucuronosyltransferase in liver were observed in both the PB and DEHP groups. One of the assumed mechanisms inducing thyroid effects is predictable to be secondary changes based on the enhancement in thyroid hormone metabolism via the induction of hepatic microsomal enzymes. No reproductive systemrelated changes in organ weights, histopathology, and sexual maturation were observed in both groups. Lower testosterone level was observed in the PB group. CYP2B and CYP3A, which are involved in testosterone metabolism, were induced in liver of the PB group. There was no change of 17β-hydroxysteroid dehydrogenase activity in testis of both groups. Lower testosterone level in the PB-treated male rats was attributed to an indirect, hepatotoxicity-associated effect on the reproductive system and not to direct effects on testis such as the antiandrogenic activity and the inhibition of steroidogenesis. These results did not indicate that PB or DEHP exposure affects the endocrine system directly.

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“…We assessed the relationship between TRIP13 and phenanthrene in the HTR-8/SVneo cell line, which has previously been used for in vitro studies of other PAHs ( J.-Y. Jo et al 2011 ) and expresses receptors and enzymes responsible for metabolism of phenanthrene ( data not shown ).…”

Section: Resultsmentioning

confidence: 99%