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.