Objective To investigate the role and the mechanisms underlyingmethylprednisolone (MP) protecting mice against lipopolysaccharide (LPS)-induced acute liver injury.
Materials and methods A total of 45 male C57BL/6 mice were randomly divided into control group and LPS-treated groups for indicated time ( LPS 2h, 4h, 8h, 24h). To investigate the effect of MP on LPS-induced liver injury, the mice were randomly divided into four groups (control, LPS, MP, LPS+MP). Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), non-esterified fatty acid (NEFA), triglyceride (TG), and the expression of inflammatory factors in liver and key proteins involved in hepatic lipogenesis and fatty acid oxidation were determined.
Results LPS treatment induced liver injury with severity in a time-dependent manner. MP administration partially reversed LPS-induced liver injury Indicated by improved pathology of liver section and decreased serum levels of ALT, AST. Meanwhile, serum levels of NEFA, and TG were significantly decreased in LPS-treated mice after MP administration compared with LPS-treated mice. Moreover, the mRNA and protein levels of fatty acid synthase (FASn), stearoyl-CoA desaturase-1(SCD-1) and peroxisome proliferator-activated receptor gamma (PPAR-γ) were significantly suppressed in livers of mice treated by LPS for 24h, which were partly reversed by MP administration. In addition, the carnitine palmitoyltransferase I (CPT-1) mRNA level was significantly up-regulated in livers of mice in LPS+MP group. In terms of mechanism, the mRNA levels of tumor necrosis factor alpha (TNF-α), interleukin 1beta (IL-1β) and IL-6 were decreased in livers of mice in LPS+MP group compared with LPS group. And the expression of Beclin-1 and LC3II/I involved in autophagy were activated in livers of mice in LPS+MP group compared with LPS group.
Conclusion Methylprednisolone protects mice against LPS-induced liver injury possible contributed by regulating hepatic lipid metabolic homeostasis and autophagy.