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 Na2SeO3 via gavage three times per week for 4 weeks. Changes in H2Se,
NADPH, and H2O2 levels were monitored in real time by using NIR-H2Se, DCI-MQ-
NADPH, and H2O2 probes in vivo, respectively. H2Se continuously accumulated in the liver throughout the Na2SeO3 treatment period, but the levels of
NADPH and H2O2 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 Na2SeO3 treatment. Therefore, the
therapeutic effect of Na2SeO3 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 the in vivo function of Na2SeO3 and the prevention of
liver fibrosis by administering inorganic
selenium.