Sodium selenite has alleviating effects on liver fibrosis;however,its therapeutic molecular mechanism remains unclear.Herein,hydrogen selenide,a major metabolite of Na_(2)SeO_(3),was tested to uncouple the sulfilimine...Sodium selenite has alleviating effects on liver fibrosis;however,its therapeutic molecular mechanism remains unclear.Herein,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 weeks.Changes 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)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 Na_(2)SeO_(3)treatment.Therefore,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 degradation.This 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.展开更多
基金the National Natural Science Foundation of China(21575081,21775091,21535004 and 91753111)the Key Research and Development Program of Shandong Province(2018YFJH0502).
文摘Sodium selenite has alleviating effects on liver fibrosis;however,its therapeutic molecular mechanism remains unclear.Herein,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 weeks.Changes 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)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 Na_(2)SeO_(3)treatment.Therefore,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 degradation.This 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.
