), Mingfu Wang()• Glycidol at sublethal concentrations triggered endothelial-to-mesenchymal transition in HUVECs.
• Glycidol at cytotoxic doses induced apoptosis and inflammation in HUVECs.
• Glycidol activated the NF-κB/MAPK signaling possibly mediated by oxidative stress
• 6-C-(E-fluorostyryl)naringenin alleviated glycidol-induced endothelial injuries.
Glycidol is a common lipid-derived foodborne toxicant mainly presents in refined oils and related foodstuffs. Vascular endothelial cells may be potential targets of the deleterious effects associated with glycidol exposure. In human umbilical vein endothelial cells (HUVECs), we found that glycidol treatment promoted endothelialto-mesenchymal transition (EndMT) at a lower concentration (0.5 mmol/L), while induced apoptosis and inflammation at a higher concentration (1 mmol/L). These harmful effects were achieved by the activation of NF-κB/MAPK signaling pathway and were mediated by reactive oxygen species (ROS). In addition, the protective potential of 6-C-(E-2-fluorostyryl)naringenin (6-CEFN) against glycidol was evaluated and compared with naringenin. HUVECs pre-treated with 6-CEFN, but not naringenin, displayed resistance to endothelial dysfunction caused by glycidol.
R. Weißhaar, R. Perz, Fatty acid esters of glycidol in refined fats and oils, Eur. J. Lipid Sci. Technol. 112(2) (2010) 158-165. https://doi.org/10.1002/ejlt.200900137.
H. Wallace, A. Jan, L. Barregård, et al., Risks for human health related to the presence of 3- and 2-monochloropropanediol (MCPD), and their fatty acid esters, and glycidyl fatty acid esters in food, EFSA Journal 14(5) (2016) 4426-4585. https://doi.org/10.2903/j.efsa.2016.4426.
Y. Shimamura, R. Inagaki, H. Honda, et al., 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? Toxics 8(4) (2020) 119. https://doi.org/10.3390/toxics8040119.
J. Aasa, D. Vare, H.V. Motwani, et al., Quantification of the mutagenic potency and repair of glycidol-induced DNA lesions, Mutat. Res. Genet. Toxicol. Environ. Mutagen. 805 (2016) 38-45. https://doi.org/10.1016/j.mrgentox.2016.05.011.
C. Sevim, M. Ozkaraca, M. Kara, et al., Apoptosis is induced by sub-acute exposure to 3-MCPD and glycidol on Wistar Albino rat brain cells, Environ. Toxicol. Pharmacol. 87 (2021) 103735. https://doi.org/10.1016/j.etap.2021.103735.
P.W. Liu, C.I. Li, K.C. Huang, et al., 3-MCPD and glycidol coexposure induces systemic toxicity and synergistic nephrotoxicity via NLRP3 inflammasome activation, necroptosis, and autophagic cell death, J. Hazard. Mater. 405 (2021) 124241. https://doi.org/10.1016/j.jhazmat.2020.124241.
R. Liu, M. Cheng, K.S.D. Kothapalli, et al., Glycerol derived process contaminants in refined coconut oil induce cholesterol synthesis in HepG2 cells, Food Chem. Toxicol. 127 (2019) 135-142. https://doi.org/10.1016/j.fct.2019.03.005.
S.J. Kwack, S.S. Kim, Y.W. Choi, et al., Mechanism of antifertility in male rats treated with 3-monochloro-1, 2-propanediol (3-MCPD), J. Toxicol. Env. Health Part A 67(23/24) (2004) 2001-2011. https://doi.org/10.1080/15287390490514651.
B. Hennig, M. Toborek, A.A. Cader, et al., Nutrition, endothelial cell metabolism, and atherosclerosis, Crit. Rev. Food Sci. Nutr. 34(3) (1994) 253-282. https://doi.org/10.1080/10408399409527663.
Y. Hu, G. Zhao, L. Qin, et al., Trans, trans-2, 4-decadienal induces endothelial cell injury by impairing mitochondrial function and autophagic flux, Food Funct. 12(12) (2021) 5488-5500. https://doi.org/10.1039/d1fo00372k.
X. Wu, C. Li, Z. Mariyam, et al., Acrolein-induced atherogenesis by stimulation of hepatic flavin containing monooxygenase 3 and a protection from hydroxytyrosol, J. Cell. Physiol. 234(1) (2018) 475-485. https://doi.org/10.1002/jcp.26600.
S. Lemaire, G. Lizard, S. Monier, et al., Different patterns of IL-1β secretion, adhesion molecule expression and apoptosis induction in human endothelial cells treated with 7α-, 7β-hydroxycholesterol, or 7-ketocholesterol, FEBS Lett. 440(3) (1998) 434-439. https://doi.org/10.1016/S0014-5793(98)01496-3.
E. Gianazza, M. Brioschi, A.M. Fernandez, et al., Lipoxidation in cardiovascular diseases, Redox Biol. 23 (2019) 101119. https://doi.org/10.1016/j.redox.2019.101119.
L. Hong, X. Du, W. Li, et al., EndMT: a promising and controversial field, Eur. J. Cell Biol. 97(7) (2018) 493-500. https://doi.org/10.1016/j.ejcb.2018.07.005.
E. Dejana, K.K. Hirschi, M. Simons, The molecular basis of endothelial cell plasticity, Nat. Commun. 8 (2017) 14361. https://doi.org/10.1038/ncomms14361.
T. Hussain, B. Tan, Y. Yin, et al., Oxidative stress and inflammation: what polyphenols can do for us? Oxidative Med. Cell. Longev. 2016 (2016) 7432797. https://doi.org/10.1155/2016/7432797.
Y. Li, X. Zou, K. Cao, et al., Curcumin analog 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one exhibits enhanced ability on Nrf2 activation and protection against acrolein-induced ARPE-19 cell toxicity, Toxicol. Appl. Pharmacol. 272(3) (2013) 726-735. https://doi.org/10.1016/j.taap.2013.07.029.
Y. Zhou, H. Xu, K.W. Cheng, et al., Acrolein evokes inflammation and autophagy-dependent apoptosis through oxidative stress in vascular endothelial cells and its protection by 6-C-(E-2-fluorostyryl)naringenin, J. Funct. Food 98 (2022) 105283. https://doi.org/10.1016/j.jff.2022.105283.
Q. Zhou, H. Xu, Y.L. Zhao, et al., 6-C-(E-phenylethenyl)-naringenin, a styryl flavonoid, inhibits advanced glycation end product-induced inflammation by upregulation of Nrf2, J. Agric. Food Chem. 70(12) (2022) 3842-3851. https://doi.org/10.1021/acs.jafc.2c00163.
Q. Zhou, H. Xu, W.Z. Yu, et al., Anti-inflammatory effect of an apigenin-Maillard reaction product in macrophages and macrophage-endothelial cocultures, Oxid. Med. Cell. Longev. 2019 (2019) 9026456. https://doi.org/10.1155/2019/9026456.
H. Xu, R.X. Deng, E.T.S. Li, et al., Pinosylvin provides neuroprotection against cerebral ischemia and reperfusion injury through enhancing PINK1/Parkin mediated mitophagy and Nrf2 pathway, J. Funct. Food 71 (2020) 104019. https://doi.org/10.1016/j.jff.2020.104019.
Y.L. Zhao, Y. Zhou, M.F. Wang, Brosimone I, an isoprenoid-substituted flavonoid, induces cell cycle G1 phase arrest and apoptosis through ROS-dependent endoplasmic reticulum stress in HCT116 human colon cancer cells, Food Funct. 10(5) (2019) 2729-2738. https://doi.org/10.1039/c8fo02315h.
C.H. Yu, M. Gong, W.J. Liu, et al., High glucose induced endothelial to mesenchymal transition in human umbilical vein endothelial cell, Exp. Mol. Pathol. 102(3) (2017) 377-383. https://doi.org/10.1016/j.yexmp.2017.03.007.
E.K. Kim, E.J. Choi, Compromised MAPK signaling in human diseases: an update, Arch. Toxicol. 89(6) (2015) 867-882. https://doi.org/10.1007/s00204-015-1472-2.
K. Chang, Q. Xie, J. Niu, et al., Heparanase promotes endothelial-to-mesenchymal transition in diabetic glomerular endothelial cells through mediating ERK signaling, Cell Death Discov. 8(1) (2022) 67. https://doi.org/10.1038/s41420-022-00858-0.
X. Wu, W.X. Cui, W. Guo, et al., Acrolein aggravates secondary brain injury after intracerebral hemorrhage through Drp1-mediated mitochondrial oxidative damage in mice, Neurosci. Bull. 36(10) (2020) 1158-1170. https://doi.org/10.1007/s12264-020-00505-7.
Y.L. Jiang, X.F. Zhou, R.C. Hu, et al., TGF-β1-induced SMAD2/3/4 activation promotes RELM-beta transcription to modulate the endothelium-mesenchymal transition in human endothelial cells, Int. J. Biochem. Cell Biol. 105 (2018) 52-60. https://doi.org/10.1016/j.biocel.2018.08.005.
P. Bernardi, F. Di Lisa, The mitochondrial permeability transition pore: molecular nature and role as a target in cardioprotection, J. Mol. Cell Cardiol. 78 (2015) 100-106. https://doi.org/10.1016/j.yjmcc.2014.09.023.
M. Mittal, M.R. Siddiqui, K. Tran, et al., Reactive oxygen species in inflammation and tissue injury, Antioxid. Redox Signal. 20(7) (2014) 1126-1167. https://doi.org/10.1089/ars.2012.5149.
P. Theofilis, M. Sagris, E. Oikonomou, et al., Inflammatory mechanisms contributing to endothelial dysfunction, Biomedicines 9(7) (2021) 781. https://doi.org/10.3390/biomedicines9070781.
M. El Assar, J. Angulo, L. Rodriguez-Manas, Oxidative stress and vascular inflammation in aging, Free Radic. Biol. Med. 65 (2013) 380-401. https://doi.org/10.1016/j.freeradbiomed.2013.07.003.
Y.L. Yin, W.W. Liu, G. Ji, et al., The essential role of p38 MAPK in mediating the interplay of oxLDL and IL-10 in regulating endothelial cell apoptosis, Eur. J. Cell Biol. 92(4/5) (2013) 150-159. https://doi.org/10.1016/j.ejcb.2013.01.001.
W. He, J. Zhang, T.Y. Gan, et al., Advanced glycation end products induce endothelial-to-mesenchymal transition via downregulating Sirt 1 and upregulating TGF-β in human endothelial cells, Biomed. Res. Int. 2015 (2015) 684242. https://doi.org/10.1155/2015/684242.
L. Gong, Y. Lei, Y. Liu, et al., Vaccarin prevents ox-LDL-induced HUVEC EndMT, inflammation and apoptosis by suppressing ROS/p38 MAPK signaling, Am. J. Transl. Res. 11(4) (2019) 2140-2154.
H.X. Liao, M.T. Zhu, Y. Chen, 4-Hydroxy-2-nonenal in food products: a review of the toxicity, occurrence, mitigation strategies and analysis methods, Trends Food Sci. Technol. 96 (2020) 188-198. https://doi.org/10.1016/j.tifs.2019.12.011.
W.W. Cheng, G.Q. Liu, L.Q. Wang, et al., Glycidyl fatty acid esters in refined edible oils: a review on formation, occurrence, analysis, and elimination methods, Compr. Rev. Food. Sci. Food Saf. 16(2) (2017) 263-281. https://doi.org/10.1111/1541-4337.12251.
T. Buhrke, K. Schultrich, A. Braeuning, et al., Comparative analysis of transcriptomic responses to repeated-dose exposure to 2-MCPD and 3-MCPD in rat kidney, liver and testis, Food Chem. Toxicol. 106 (2017) 36-46. https://doi.org/10.1016/j.fct.2017.05.028.
Y.J. Choi, M.K. Lee, Y.J. Lee, et al., Inhibition of hydrogen peroxide-induced endothelial apoptosis by 2’,4’,7-trihydroxyflavanone, a flavonoid form, J. Med. Food 7(4) (2004) 408-416. https://doi.org/10.1089/jmf.2004.7.408.
Journal Collaboration: Yao Meng (Ms.)✉️ +86-10-83470574
Technical Support: Kuo Zhao (Mr.)✉️ +86-10-83470507
Media Contact: Hao Jin (Mr.)✉️ +86-10-83470559
Address: Floor 6, Tower B, Xueyan Building, Shuangqing Road, Haidian District, Beijing 100084, China.
Copyright © 2025 Tsinghua University Press Ltd.
京公网安备11010802044758号