TRA-017, A Derivative of Tranilast, Protects against Hepatic Inflammation Induced by Lipopolysaccharide Administration

Background: Liver is considered as the main detoxification organ of human body. Hepatic inflammation is a key mechanism under many liver diseases. The present study suggested that TRA-017, a tranilast derivative, protective effects against hepatic inflammation in animal model. Therefore, TRA-017 is potential chemical or drugs treating liver diseases such as hepatitis and cirrhosis. Methods: The study was performed on Swiss albino mice brought from Pasteur Institute in Ho Chi Minh City, Vietnam. Mice were randomly divided into 4 groups: Veh, TRA-17, LPS and Treatment. To investigate the effects of TRA-017 on hepatic inflammation, we injected mice with LPS (2.5 mg/kg) every day for 5 consecutive days to induce hepatic inflammation model. TRA-017 (20 mg/kg, s.c.) was administered 1h prior to every LPS treatment. After that, we evaluated TRA-017-induced amelioration effects via investigating biochemical markers (AST, ALT, cytokines and XOD activity levels) oxidative stress markers (ROS) and H and E histopathological characteristics. Result: Our results suggested that LPS significantly increase AST, ALT, cytokines (IL-6, TNF-α, IL-1β and IFN-γ) and XOD activity levels (p less than 0.01 vs. corresponding Veh) and that pre-treament with TRA-017 significantly attenuated LPS-induced increase of AST, ALT, cytokines (IL-6, TNF-α, IL-1β and IFN-γ) and XOD activity levels (p less than 0.01 vs. corresponding LPS group). LPS also remarkably increased ROS formation (p less than 0.01 vs. corresponding Veh). Pre-treatment with TRA-017 significantly attenuated LPS-induced oxidative stress burden in the liver (p less than 0.01 vs. corresponding LPS group). Administration with LPS induced remarkably changes on histopathology of mouse liver. Pre-treatment with TRA-017 showed counteractive effects against LPS-induced histopathological changes. In conclusion, treatment with TRA-017 attenuated LPS-induced hepatic inflammation.