Protective effect of FTY720 on several markers of liver injury induced by concanavalin a in mice.

BACKGROUND: 2-Amino-2-[2-(4-octylphenyl)ethyl] propane-1,3-diol hydrochloride (FTY720) is a novel agent with protective effect on several markers of liver injury. It is a chemical substance derived by modifying myriocin from the ascomycete Isaria sinclairii. It has been reported that FTY720 is able to treat autoimmune encephalomyelitis, renal cancer, asthma, and multiple sclerosis. More potent clinical applications of FTY720 need to be investigated. OBJECTIVE: The aim of this study was to evaluate the protective effect of FTY720 on several markers of experimental liver injury and to investigate the possible mechanism of action. METHODS: Concanavalin A (Con A) at a dose of 15 mg/kg was intravenously. injected in mice, and 10 days before the Con A challenge, 1 mg/kg, 3 mg/kg, and 6 mg/kg of FTY720 were administered to mice. The liver injury was monitored biochemically by measuring serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and tumor necrosis factor-α (TNF-α) levels. TNF-α and nuclear factor-κB (NF-κB) in liver tissue were detected by Western blot analysis. RESULTS: FTY720, when administered intragastrically for 10 days in mice with Con A-induced liver injury, dose-dependently reduced serum ALT and AST and TNF-α levels. The differences were statistically significant (P ≤ 0.05). It was also found that FTY720 decreases TNF-α and NF-κB protein expression in liver tissue. CONCLUSIONS: FTY720 is able to improve several markers of Con A-induced liver injury in mice, including serum ALT, serum AST, TNF-α, and NF-κB, which might be at least in part related to its ability to reduce TNF-α/NF-κB cascade activity.