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 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 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)probesin vivo, respectively. H2Se 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 H2Se that uncoupled the sulfilimine bond to induce collagen IV degradation. This study provided a reasonable explanation for the molecular mechanism of thein vivofunction of Na(2)SeO(3)and the prevention of liver fibrosis by administering inorganic selenium.

Automated summary

The study revealed that sodium selenite (Na2SeO3) has a therapeutic effect on liver fibrosis, mainly through the metabolite hydrogen selenide (H2Se) uncoupling the sulfilimine bond in collagen IV. By monitoring changes in H2Se, NADPH, and H(2)O(2) levels in vivo, the mechanism of the therapeutic effect of Na2SeO3 on liver fibrosis was confirmed.