Protective effect of diosgenin on LPS/D-Gal-induced acute liver failure in C57BL/6 mice

Abstract

Acute liver failure (ALF) is a deadly clinical syndrome, which leads to a rapid loss of normal liver function. Diosgenin is a natural steroidal sapogenin found in various plant families. Various studies have shown that diosgenin have therapeutic or preventive effect in various diseases such as cancer, cardiovascular disorders, type 2 diabetes, and neurodegenerative disorders. In this study, we evaluated effects of diosgenin on mice model of ALF. Animal model of ALF was induced by intraperitoneal injection of lipopolysaccharide (LPS)/d-galactosamine (D-Gal). The male C57BL/6 mice were randomly divided into 3 groups: control group, LPS/D-Gal group, and LPS/D-Gal + diosgenin group (50 mg/kg). Mice in the LPS/D-Gal group received a combination of LPS (50 μg/kg) and D-Gal (400 mg/kg) intraperitoneally. LPS/D-Gal + diosgenin group received diosgenin twice orally 24 h and 1 h before receiving LPS/D-Gal. Markers of liver injury including ALT, AST and ALP were measured in blood samples in addition to determination of oxidative stress and inflammatory markers including MDA, nitrite, ROS, catalase, SOD, Nrf2, IL-1β, IL-6, TLR4, TNF-α and NF-κB in hepatic tissue. Administration of diosgenin could greatly reduce serum levels of ALT, AST, and ALP. Besides, hepatic levels of MDA, ROS, IL-1β, IL-6, TLR4, TNF-α, and NF-κB significantly decreased and SOD activity and Nrf2 level increased in comparison with the LPS/D-Gal group. In addition, myeloperoxidase activity as a marker of neutrophil infiltration decreased following diosgenin administration. In summary, diosgenin led to reduction of liver injury indices and oxidative stress and inflammatory events and diosgenin has probably hepatoprotecive effects in ALF.