The Effects And Related Mechanisms Of 1,25-（OH）₂VD₃ Against Mouse Acute Liver Failure Induced By LPS/D-GalN

Background/Aims: 1,25-（OH）₂VD₃ has been shown to inhibit the development of several immune-related diseases. Our study aims to explore the role of 1,25-（OH）₂VD₃ in LPS-induced murine liver failure, and its related immunological mechanisms.Methods: Female C57BL/6 mice were intraperitoneally injected with 1,25-（OH）₂VD₃ followed by lipopolysaccharide（LPS） treatment in the presence of D-galactosamine（D-GalN） to induce acute liver failure（ALF）, which was confirmed by assaying serum alanine transaminase levels（ALT）, liver tissue pathology, and survival. Relevant commercial kits and flow cytometry were employed to test required indicators.Results: Pre-treatment with 1,25-（OH）₂VD₃ markedly decreased serum ALT levels, measurably attenuated histological liver injury, and significantly extended survival times. Depletion of macrophages counteracted LPS/D-GalN- induced ALF. 1,25-（OH）₂VD₃ acted directly on macrophages and inhibited the expression of toll-like receptor 4（TLR4） after LPS stimulation. It also weakened subsequent inflammatory pathways: lower levels of tumor necrosis factor alpha（TNF-α） and interleukin-6（IL-6） were detected in the serum and supernatant, compared with vehicle control group.Conclusions: Our study shows that 1,25-（OH）₂VD₃ attenuated LPS/D-GalN-induced liver failure partly through inhibiting TLR4 expression on macrophages after LPS stimulation. However, further studies are required to establish the mechanisms of 1,25-（OH）₂VD₃ protection with more detail and accuracy.