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Hydrogen selenide,a vital metabolite of sodium selenite,uncouples the sulfilimine bond and promotes the reversal of liver fibrosis

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Science China(Life Sciences) 2021年第3期64卷 443-451页

作者： Dongrui Luan zengteng zhao Dandan Xia Qiuling Zheng Xiaonan Gao Kehua Xu Bo Tang College of Chemistry Chemical Engineering and Materials ScienceCollaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of ShandongKey Laboratory of Molecular and Nano ProbesMinistry of EducationInstitute of Molecular and Nano ScienceShandong Normal UniversityJinan 250014China Department of Pharmaceutical Analysis School of PharmacyState Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China

Sodium selenite has alleviating effects on liver fibrosis;however,its therapeutic molecular mechanism remains ***,hydrogen selenide,a major metabolite of Na_(2)SeO_(3),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 CCl_(4)-induced method,followed by the administration of 0.2 mg kg−1 Na_(2)SeO_(3)via gavage three times per week for 4 *** in H2Se,NADPH,and H_(2)O_(2)levels were monitored in real time by using NIR-H2Se,DCI-MQ-NADPH,and H_(2)O_(2)probes in vivo,respectively.H_(2)Se continuously accumulated in the liver throughout the Na_(2)SeO_(3)treatment period,but the levels of NADPH and H_(2)O_(2)*** expression of collagen IV was analyzed through Western blot and liquid chromatography-mass *** confirmed that the sulfilimine bond of collagen IV in the fibrotic mouse livers could be broken by H2Se with the Na_(2)SeO_(3)***,the therapeutic effect of Na_(2)SeO_(3)on liver fibrosis could be mainly attributed to H_(2)Se that uncoupled the sulfilimine bond to induce collagen IV *** study provided a reasonable explanation for the molecular mechanism of the in vivo function of Na_(2)SeO_(3)and the prevention of liver fibrosis by administering inorganic selenium.

关键词： hydrogen selenide sodium selenite sulfilimine bond liver fibrosis reversal collagen IV

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