Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jan 15:2021:8839394.
doi: 10.1155/2021/8839394. eCollection 2021.

1-O-Hexyl-2,3,5-Trimethylhydroquinone Ameliorates the Development of Preeclampsia through Suppression of Oxidative Stress and Endothelial Cell Apoptosis

Lai Jiang  1 , Yanping Gong  2 , Jie Rao  3 , Qiuhong Yang  4 , Na Gao  1 , Guiyang Li  1 , Yuyan Ma  1
Affiliations

1-O-Hexyl-2,3,5-Trimethylhydroquinone Ameliorates the Development of Preeclampsia through Suppression of Oxidative Stress and Endothelial Cell Apoptosis

Lai Jiang et al. Oxid Med Cell Longev. .

Abstract

1-O-Hexyl-2,3,5-trimethylhydroquinone (HTHQ), a potent nuclear factor-E2-related factor 2 (Nrf2) activator, has potent antioxidant activity by scavenging reactive oxygen species (ROS). However, the role of HTHQ on the development of preeclampsia (PE) and the underlying mechanisms have barely been explored. In the present study, PE model was induced by adenovirus-mediated overexpression of soluble fms-like tyrosine kinase 1 (sFlt-1) in pregnant mice. The results showed that HTHQ treatment significantly relieved the high systolic blood pressure (SBP) and proteinuria and increased the fetal weight and fetal weight/placenta weight in preeclamptic mice. Furthermore, we found that HTHQ treatment significantly decreased soluble endoglin (sEng), endothelin-1 (ET-1), and activin A and restored vascular endothelial growth factor (VEGF) in preeclamptic mice. In addition, HTHQ treatment inhibited oxidative stress and endothelial cell apoptosis by increasing the levels of Nrf2 and its downstream haemoxygenase-1 (HO-1) protein. In line with the data in vivo, we discovered that HTHQ treatment attenuated oxidative stress and cell apoptosis in human umbilical vein endothelial cells (HUVECs) following hypoxia and reperfusion (H/R), and the HTHQ-mediated protection was lost after transfected with siNrf2. In conclusion, these results suggested that HTHQ ameliorates the development of preeclampsia through suppression of oxidative stress and endothelial cell apoptosis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of this article.

Figures

Figure 1
Figure 1
HTHQ treatment ameliorated PE development in vivo. (a) The systolic blood pressure (SBP) of mice was detected in each group (n = 8). (b) The fetal weight of mice was detected in each group (n = 8). (c) The fetal weight/placenta weight ratio of mice was detected in each group (n = 8). (d) The proteinuria of mice was detected in each group (n = 8). ∗∗P < 0.01 vs. the control group; #P < 0.05 and ##P < 0.01 vs. the PE group.
Figure 2
Figure 2
HTHQ treatment attenuated decreases the concentration of sEng, ET-1, and activin A levels and restored VEGF levels in blood from PE animals. ELISA was used to detect the concentration of sEng (a), VEGF (b), ET-1 (c), and activin A (d) in serum of mice in each group (n = 6). ∗∗P < 0.01 vs. the control group; #P < 0.05 and ##P < 0.01 vs. the PE group.
Figure 3
Figure 3
HTHQ treatment attenuated oxidative stress induced by PE. DHE staining was used to assess the ROS production in each group (n = 6). The levels of SOD (b), CAT (c), MDA (d), and GSH (e) in each group (n = 6). ∗∗P < 0.01 vs. the control group; #P < 0.05 and ##P < 0.01 vs. the PE group.
Figure 4
Figure 4
HTHQ treatment decreased placental apoptosis. (a, b) TUNEL staining was used to measure the placental apoptosis in each group (n = 4). ∗∗P < 0.01 vs. the control group; #P < 0.05 and ##P < 0.01 vs. the PE group.
Figure 5
Figure 5
HTHQ treatment attenuated oxidative stress and apoptosis in HUVECs following H/R. The levels of SOD (a), catalase CAT (b), and MDA (c) in each group (n = 6). (d) Images and quantifications of TUNEL staining in each group (n = 6). ∗∗P < 0.01 vs. the control group; #P < 0.05 and ##P < 0.01 vs. the H/R group.
Figure 6
Figure 6
HTHQ activates Nrf2 antioxidant pathway. (a) Western blots showing the level of Nrf2 and HO-1 in mice of each group (n = 4). (b) Western blots showing the level of Nrf2 and HO-1 in each group (n = 4). ∗∗P < 0.01 vs. the control group; ##P < 0.01 vs. the H/R group.
Figure 7
Figure 7
HTHQ induces translocation of Nrf2. (a) Western blots showing the level of nuclear-Nrf2 and cytoplasm-Nrf2 in mice of each group (n = 4). (b) Western blots showing the level of nuclear-Nrf2 and cytoplasm-Nrf2 in each group (n = 4). (d) Immunofluorescence staining was used to assess the translocation of Nrf2 in each group (n = 6). ∗P < 0.05 vs. the control group; ∗∗P < 0.01 vs. the PE or H/R group.
Figure 8
Figure 8
The protection of HTHQ involves the Nrf2/HO-1 pathway. The levels of SOD (a), catalase CAT (b), and MDA (c) in HUVECs after si-Nrf2 transfection (n = 6). (d) Images and quantifications of TUNEL staining in HUVECs after si-Nrf2 transfection (n = 6). ∗P < 0.05 vs. the H/R group; ∗∗P < 0.01 vs. the H/R group.
Figure 9
Figure 9
HTHQ suppresses oxidative stress and endothelial cell apoptosis and subsequent improvement of PE through activation of Nrf2/HO-1 signaling.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Wedenoja S., Yoshihara M., Teder H., et al. Fetal _HLA-G_ mediated immune tolerance and interferon response in preeclampsia. EBioMedicine. 2020;59:p. 102872. doi: 10.1016/j.ebiom.2020.102872. - DOI - PMC - PubMed
    1. Phoswa W. N. Dopamine in the Pathophysiology of Preeclampsia and Gestational Hypertension: Monoamine Oxidase (MAO) and Catechol-O-methyl Transferase (COMT) as Possible Mechanisms. Oxidative Medicine and Cellular Longevity. 2019;2019:8. doi: 10.1155/2019/3546294.3546294 - DOI - PMC - PubMed
    1. Yang S., Song L., Shi X., Zhao N., Ma Y. Ameliorative effects of pre-eclampsia by quercetin supplement to aspirin in a rat model induced by L-NAME. Biomedicine & Pharmacotherapy. 2019;116:p. 108969. doi: 10.1016/j.biopha.2019.108969. - DOI - PubMed
    1. Yang X., Yang Y., Yuan Y., Liu L., Meng T. The Roles of Uterine Natural Killer (NK) Cells and KIR/HLA-C Combination in the Development of Preeclampsia: A Systematic Review. BioMed Research International. 2020;2020:10. doi: 10.1155/2020/4808072.4808072 - DOI - PMC - PubMed
    1. Viana-Mattioli S., Nunes P., Cavalli R., Sandrim V. Analysis of SIRT1 Expression in Plasma and in an In Vitro Model of Preeclampsia. Oxidative Medicine and Cellular Longevity. 2020;2020:7. doi: 10.1155/2020/4561083.4561083 - DOI - PMC - PubMed

MeSH terms