Hydrogen selenide, a vital metabolite of sodium selenite, uncouples the sulfilimine bond and promotes the reversal of liver fibrosis
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 H 2 Se, NADPH, and H 2 O 2 levels were monitored in real time by using NIR-H 2 Se, 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 H 2 Se 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.
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