Ezetimibe counteracts lipopolysaccharide-induced liver injury in mice via modulating TLR4-mediated MYD88/TRAF-6/NF-kB signaling pathway.

Sepsis-associated liver injury is one of the signs of multiple organ damage brought on by sepsis. Acute liver injury (ALI) is a potentially fatal acute inflammatory disease that causes necrotic cell death and immediate hepatocyte destruction. This study aimed to investigate the protective effect of ezetimibe (EZE) against lipopolysaccharide (LPS)-induced acute liver injury. Five days prior to a single intraperitoneal injection of LPS (3 mg/kg), male Swiss albino mice weighing 18-25 g were pre-treated orally with EZE at two different dosages (5 and 10 mg/kg), while animals of the control group received only the vehicles. Serum was used to test liver function, while mouse tissue homogenates were used to measure oxidative stress and inflammatory mediators. EZE improved histological changes and dramatically reduced serum liver transaminases. Reduced levels of malondialdehyde (MDA) and increased levels of reduced glutathione (GSH) in hepatic tissues are further indications of its antioxidant action. Moreover, EZE pretreatment significantly reduced the hepatic expression of toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB)p65, interleukin (IL)-1β and tumor necrosis factor (TNFα). Additionally, myeloid differentiation primary-response protein 88 (MYD88), TNF Receptor Associated Factor 6 (TRAF-6) and IL-6 were markedly reduced in the liver by EZE. Collectively, EZE may be a promising candidate in sepsis-related liver injury following further clinical studies.