Glucocorticoids Alleviates Lipopolysaccharide-Induced Acute Liver Injury Associated With Promoting The Expression Of Ntcp And Bsep

Background: Methylprednisolone (MP) is a glucocorticoid steroid administered usually in severe sepsis and septic shock. However, the role and molecular mechanisms underlying hepatoprotective effect of MP in sepsis-induced acute liver injury (ALI) is largely unknown. The aim of the present study was to investigate the effect of MP in a mouse model of lipopolysaccharides (LPS)-induced ALI. Methods: A total of 96 male C57BL/6J mice were randomly divided into four groups (n=24 per group) according to the treatment including vehicle (control group) or LPS only (LPS group) or LPS with 2 mg/kg MP (LPS+2 mg/kg MP group) or LPS with 20 mg/kg MP (LPS+20 mg/kg MP group) three times at 1 h, 24 h, 48 h after LPS treatment. The livers and serum were collected for further analysis. Serum levels of total bilirubin (TBIL), total bile acid (TBA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at 24 h, 48 h or 72 h after LPS administration. Histological examinations were performed on liver, and liver sections were stained with hematoxylin & eosin (HE). Furthermore, the expression of Interleukin-6 (IL-6), Tumour Necrosis Factor-alpha (TNF-alpha), sodium-taurocholate co-transporting polypeptide (NTCP) and bile salt export pump (BSEP) in liver was analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. Results: MP therapy protects mice against LPS-induced ALI at the dose of 2 mg/kg and 20 mg/kg. The serum TBIL, TBA, ALT, AST levels were significantly decreased in LPS+2 mg/kg MP group and LPS+20 mg/kg MP group compared with LPS group. However, there is no significant difference between the LPS+2 mg/kg MP group and the LPS+ 20 mg/kg MP group. Furthermore, LPS administration suppresses the expression of NTCP and BSEP, which is significantly reversed by MP therapy. Moreover, LPS-induced higher expression of IL-6 and TNF-a was significantly suppressed by MP administration. Conclusion: MP protects mice against LPS-induced ALI and improves bile acid secretion and transportation, partially due to the upregulated expression of NTCP and BSEP.