Does External Exposure of Glycidol-Related Chemicals Influence the Forming of the Hemoglobin Adduct, N-(2,3-dihydroxypropyl)valine, as a Biomarker of Internal Exposure to Glycidol?

Shimamura, Yuko; Inagaki, Ryo; Honda, Hiroshi; Masuda, S.

doi:10.3390/toxics8040119

Cited by 9 publications

(8 citation statements)

References 36 publications

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“…Therefore, in verifying the relationship between lipase activity and the release of glycidol from GEs, the lipase activity and diHOPrVal in blood were measured in C57/BL6J mice fed a HFD for 8 weeks. A previous study showed that when glycidyl oleate was administered to rats at 0.5 and 1.0 mmol/kg b.w., the level of diHOPrVal in the blood at 24 h was 419 ± 50 and 1055 ± 110 pmol/g globin, respectively [ 36 ]. Therefore, mice fed with HFD were orally administered glycidyl oleate dissolved in soybean oil at doses of 0, 0.1, 0.5, and 1.0 mmol/kg b.w.…”

Section: Discussionmentioning

confidence: 99%

Potential Role of Lipase Activity on the Internal Exposure Assessment of Glycidol Released from Its Fatty Acid Esters

Shimamura

Inagaki

Oike

et al. 2023

Toxics

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Glycidyl fatty acid esters (GEs) can be found in food, and they can be converted into genotoxic animal carcinogen glycidol in vivo by the action of lipase. This study examined whether human ingestion of charbroiled pork containing high levels of GEs (300 µg/day) increased glycidol–hemoglobin adduct (diHOPrVal), a marker of internal exposure to glycidol using LC-MS/MS. Contrary to expectation, the diHOPrVal value before ingesting charbroiled pork was 3.11 ± 1.10 pmol/g globin, which slightly decreased to 2.48 ± 0.47 pmol/g globin after 5 days of consumption. The decrease in lipase activity caused by the continuous consumption of lipid-rich foods such as meat in humans might decrease internal exposure to glycidol released from its esters. Thus, lipase activity was measured in C57/BL6J mice fed a high-fat diet (HFD) for 8 weeks, and diHOPrVal formation was measured after the administration of glycidyl oleate. Lipase activity was significantly lower in the HFD group than in the normal diet group. The amount of diHOPrVal was reduced in the HFD group. Therefore, the lipase activity was reduced by HFD, thereby decreasing the degradation of glycidol from glycidyl oleate. These results indicate that changes in lipase activity depending on the amount of lipids in the diet may affect the assessment of GEs exposure, and monitoring the lipase activity would provide a comprehensive understanding of exposure assessment.

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Section: Discussionmentioning

confidence: 99%

Potential Role of Lipase Activity on the Internal Exposure Assessment of Glycidol Released from Its Fatty Acid Esters

Shimamura

Inagaki

Oike

et al. 2023

Toxics

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“…The 2,3-hydroxypropyl substituents are formed upon food treatment, they covalently attach into Val and were found as N-2, 3-dihydroxypropyl Val residues in hemoglobin. This derivative was considered as a marker in food examination [39]. Neither in this toxicological study nor in other cases [40] the enantiomerically pure gl derivatives were studied separately.…”

Section: Time-dependent Cellular Accumulationmentioning

confidence: 99%

Chiral Recognition of Homochiral Poly (amidoamine) Dendrimers Substituted with R- and S-Glycidol by Keratinocyte (HaCaT) and Squamous Carcinoma (SCC-15) Cells In Vitro

et al. 2021

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The generation 2 and 3 poly(amidoamine) dendrimers (PAMAM G2 and G3) were converted into N-(2,3-dihydroxy)propyl derivatives by the addition of enantiomerically pure S- and R-glycidol. The homochiral dendrimers bind to HaCaT and SCC-15 cell membranes with an R/S glycidol enantioselectivity ratio of 1.5:1, as was quantitatively determined by fluorescence microscopy and visualized by confocal microscopy. Fully substituted G2 and G3 dendrimers were equipped with 32 and 64 N-(2,3-dihydroxy)propyl residues and showed effectively radial symmetry for homochiral derivatives in 13C NMR spectrum in contrary to analogs obtained by reaction with rac-glycidol. The sub-stoichiometric derivatives of G2 and G3 were also obtained in order to characterize them spectroscopically. The homochiral dendrimers were labeled with two different fluorescent labels, fluorescein, and rhodamine B, using their isothiocyanates to react with G2 and G3 followed by the addition of S- and R-glycidol. Obtained fluorescent derivatives were deficiently filled with N-(2,3-dihydroxy)propyl substituents due to steric hindrance imposed by the attached label. Nevertheless, these derivatives were used to determine their ability to bind to the cell membrane of human keratinocytes (HaCaT) and squamous carcinoma cells (SCC-15). Confocal microscopy images obtained from cells treated with variously labeled conjugates and fluorescence analysis with fluorescence reader allowed us to conclude that R-glycidol derivatives were bound and entered the cells preferentially, with higher accumulation in cancer cells. The G3 polyamidoamine (PAMAM)-based dendrimers were taken up more efficiently than G2 derivatives. Moreover, S- and R-glycidol furnished dendrimers were highly biocompatible with no toxicity up to 300 µM concentrations, in contrast to the amine-terminated PAMAM analogs.

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“…In our previous study, diHOPrVal was not produced from chemicals other than glycidol or glycidol-related chemicals (epichlorohydrin, propylene oxide, 1-bromopropane, allyl alcohol, fructose, and glyceraldehyde), although a single dose of these chemicals was administered to rats (Shimamura et al, 2020).…”

Section: Several Chemicals Have Been Proposed As Possible Precursorsmentioning

confidence: 99%

“…In our previous study, diHOPrVal was not produced from chemicals other than glycidol or glycidol‐related chemicals (epichlorohydrin, propylene oxide, 1‐bromopropane, allyl alcohol, fructose, and glyceraldehyde), although a single dose of these chemicals was administered to rats (Shimamura et al., 2020 ). Humans are routinely exposed to these chemicals and it is possible that the amount of diHOPrVal produced is small following a single administration to experimental animals.…”

Section: Introductionmentioning

confidence: 99%

A comparison of the exposure system of glycidol‐related chemicals on the formation of glycidol‐hemoglobin adducts

Shimamura,

Wada,

Tashiro

et al. 2023

Food Science & Nutrition

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Glycidol fatty acid esters that are present in foods are degraded in vivo to the animal carcinogen glycidol, which binds to the N‐terminal valine of hemoglobin (Hb) to form N‐(2,3‐dihydroxypropyl)valine (diHOPrVal) adducts. The existence of other chemicals that are converted to glycidol is unknown. To determine the effect of different exposure conditions on the formation of diHOPrVal adducts, several glycidol‐related chemicals (3‐monochloropropane‐1,2‐diol; 3‐MCPD, epichlorohydrin, glyceraldehyde, acrylic acid, and 1,2‐propanediol) were evaluated using in vitro and in vivo (single/repeated dose) methods. In vitro, the reaction of 3‐MCPD or epichlorohydrin with human Hb produced 17% and 0.7% of diHOPrVal, as compared to equimolar glycidol, respectively. Following a single administration of glycidol‐related compounds to ICR mice, diHOPrVal formation was observed only in the epichlorohydrin‐treated group after day 5 of exposure. After 14 days of repeated dosing, the amounts of diHOPrVal produced by epichlorohydrin and 3‐MCPD in vivo were <1% of diHOPrVal produced by an equal molar concentration of glycidol. Furthermore, glyceraldehyde group produced 0.2% of diHOPrVal at the same molar concentration of glycidol equivalents, in which diHOPrVal formation could not be confirmed by the in vitro assay. The results indicate the usefulness of diHOPrVal as an exposure marker for glycidol; however, the contribution of its formation in vivo by exposure to various chemicals will be necessary to validate and interpret the results.

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Does External Exposure of Glycidol-Related Chemicals Influence the Forming of the Hemoglobin Adduct, N-(2,3-dihydroxypropyl)valine, as a Biomarker of Internal Exposure to Glycidol?

Cited by 9 publications

References 36 publications

Potential Role of Lipase Activity on the Internal Exposure Assessment of Glycidol Released from Its Fatty Acid Esters

Potential Role of Lipase Activity on the Internal Exposure Assessment of Glycidol Released from Its Fatty Acid Esters

Chiral Recognition of Homochiral Poly (amidoamine) Dendrimers Substituted with R- and S-Glycidol by Keratinocyte (HaCaT) and Squamous Carcinoma (SCC-15) Cells In Vitro

A comparison of the exposure system of glycidol‐related chemicals on the formation of glycidol‐hemoglobin adducts

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