Abstract
This study aimed to explore the effects of fucoidan from Fucus vesiculosus on concanavalin A (ConA)-induced acute liver injury in mice. Pretreatment with fucoidan protected liver function indicated by ALT, AST and histopathological changes by suppressing inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). In addition, intrinsic and extrinsic apoptosis mediated by Bax, Bid, Bcl-2, Bcl-xL and Caspase 3, 8, and 9 were inhibited by fucoidan and the action was associated with the TRADD/TRAF2 and JAK2/STAT1 signal pathways. Our results demonstrated that fucoidan from Fucus vesiculosus alleviated ConA-induced acute liver injury via the inhibition of intrinsic and extrinsic apoptosis mediated by the TRADD/TRAF2 and JAK2/STAT1 pathways which were activated by TNF-α and IFN-γ. These findings could provide a potential powerful therapy for T cell-related hepatitis.
Highlights
Liver injury is the basis of acute liver failure
Decreased edema and necrosis were noted with increased fucoidan concentration at each time point, which demonstrated that fucoidan pretreatment effectively improved acute injury caused by concanavalin A (ConA) and protected liver cells from damage
We demonstrated that fucoidan pretreatment may protect against ConA-induced acute liver injury by inhibiting both intrinsic and extrinsic apoptosis using a well-established model and showed the significance of drug screening for T lymphocyte-dependent injury
Summary
Liver injury is the basis of acute liver failure. Severe and persistent liver damage eventually leads to liver failure. The incidence of autoimmune and viral hepatitis which can develop into cirrhosis and even lead to death has risen sharply. The pathogenesis of these diseases is associated with the cytotoxic effect of sensitized T lymphocytes and pro-inflammatory cytokines produced by endotoxin-stimulated macrophages [2]. Three types of inducers, including concanavalin A (ConA), D-galactosamine (D-GalN)/lipopolysaccharides (LPS) and high dose LPS were used to simulate the pathological processes in acute liver injury. Of these inducers, ConA which is characterized by easy establishment, obvious change in liver enzymes and cytokine
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