Abstract

Background Sepsis-induced liver dysfunction is believed to be an independent risk factor for multiple organ dysfunction and death. Idebenone (IDE), a synthetic analog of coenzyme Q10 (CoQ10), possesses an antioxidizing property. The present study aimed to investigate the efficacy of IDE on sepsis-induced liver injury and discuss its reaction mechanism in vivo and in vitro . Methods To establish an in vivo model of sepsis-induced liver injury, rats were treated with high-grade cecal ligation and puncture (CLP). Hematoxylin-eosin staining was applied to observe the liver pathological changes, and liver function was examined using alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) assay kits. Enzyme-linked immunosorbent assay (ELISA) kits were employed to assess the levels of inflammatory cytokines in serum and tissues. The activities of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were analyzed using MDA, SOD, and GSH-Px assay kits, respectively. The apoptosis of liver tissues was measured by terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) staining, and western blot was employed to estimate apoptosis-related proteins. In vitro , 0.5 μg/mL lipopolysaccharide (LPS) was adopted to administrate primary hepatocytes. The expressions of receptor for advanced glycation end products (RAGE)/p38-related proteins were evaluated by western blot. Cell counting kit-8 (CCK-8) and dichloro-dihydro-fluorescein diacetate (DCFH-DA) assays were utilized to estimate cell viability and reactive oxygen species ( ROS ) content. Moreover, the transfection efficacy of overexpression (Ov)- RAGE in primary hepatocytes was tested by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Results IDE could improve liver function and reduce sepsis-induced pathological damage. The levels of tumor necrosis factor-α ( TNF-α ), interleukin-1β ( IL-1β ), and interleukin-6 ( IL-6 ) in the