Hydrogen selenide, a vital metabolite of sodium selenite, uncouples the sulfilimine bond and promotes the reversal of li
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drogen selenide, a vital metabolite of sodium selenite, uncouples the sulfilimine bond and promotes the reversal of liver fibrosis 1
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Dongrui Luan , Zengteng Zhao , Dandan Xia , Qiuling Zheng , Xiaonan Gao , Kehua Xu & 1 Bo Tang 1
College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical
Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Molecular and Nano 2
Science, Shandong Normal University, Jinan 250014, China; Department of Pharmaceutical Analysis, School of Pharmacy, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China Received March 23, 2020; accepted June 20, 2020; published online September 1, 2020
Sodium selenite has alleviating effects on liver fibrosis; however, its therapeutic molecular mechanism remains unclear. Herein, hydrogen selenide, a major metabolite of Na2SeO3, was tested to uncouple the sulfilimine bond in collagen IV, the biomarker of liver fibrosis. A mouse model of liver fibrosis was constructed via a CCl4-induced method, followed by the administration of −1 0.2 mg kg Na2SeO3 via gavage three times per week for 4 weeks. Changes in H2Se, NADPH, and H2O2 levels were monitored in real time by using NIR-H2Se, DCI-MQ-NADPH, and H2O2 probes in vivo, respectively. H2Se continuously accumulated in the liver throughout the Na2SeO3 treatment period, but the levels of NADPH and H2O2 decreased. The expression of collagen IV was analyzed through Western blot and liquid chromatography-mass spectrometry. Results confirmed that the sulfilimine bond of collagen IV in the fibrotic mouse livers could be broken by H2Se with the Na2SeO3 treatment. Therefore, the therapeutic effect of Na2SeO3 on liver fibrosis could be mainly attributed to H2Se that uncoupled the sulfilimine bond to induce collagen IV degradation. This study provided a reasonable explanation for the molecular mechanism of the in vivo function of Na2SeO3 and the prevention of liver fibrosis by administering inorganic selenium. hydrogen selenide, sodium selenite, sulfilimine bond, liver fibrosis reversal, collagen IV Citation:
Luan, D., Zhao, Z., Xia, D., Zheng, Q., Gao, X., Xu, K., and Tang, B. (2020). Hydrogen selenide, a vital metabolite of sodium selenite, uncouples the sulfilimine bond and promotes the reversal of liver fibrosis. Sci China Life Sci 63, https://doi.org/10.1007/s11427-019-1761-1
INTRODUCTION Collagen IV, as a major constituent of basement membranes (Bhave et al., 2012; Fidler et al., 2017; McCall et al., 2014; Vanacore et al., 2009), is evaluated as an important biomarker of liver fibrosis (Veidal et al., 2011). During the early stage of fibrosis, collagen IV plays an active role in stimulating disease progression (Hahn et al., 1980; Rojkind et al., 1979; Seyer et al., 1977; Wells, 2008; Zeisberg et al.,
2006). However, many current studies focus on the relationship between the expression level of other types of collage
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