Sinapic acid ameliorates D-galactosamine/lipopolysaccharide-induced fulminant hepatitis in rats: Role of nuclear factor erythroid-related factor 2/heme oxygenase-1 pathways

BACKGROUND Sinapic acid (SA) has been shown to have various pharmacological properties such as antioxidant, antifibrotic, anti-inflammatory, and anticancer activities. Its mechanism of action is dependent upon its ability to curb free radical production and protect against oxidative stress-induced tissue injuries. AIM To study the hepatoprotective effects of SA against lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver failure (ALF) in rats. METHODS Experimental ALF was induced with an intraperitoneal (i.p.) administration of 8 mu g LPS and 800 mg/kg D-GalN in normal saline. SA was administered orally once daily starting 7 d before LPS/D-GalN treatment. RESULTS Data showed that SA ameliorates acute liver dysfunction, decreases serum levels of alanine transaminase (ALT), and aspartate aminotransferase (AST), as well as malondialdehyde (MDA) and NO levels in ALF model rats. However, pretreatment with SA (20 mg/kg and 40 mg/kg) reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) activation and levels of inflammatory cytokines (tumor necrosis factor-alpha and interleukin 6). Also, SA increased the activity of the nuclear factor erythroid-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway. CONCLUSION In conclusion, SA offers significant protection against LPS/D-GalN-induced ALF in rats by upregulating Nrf2/HO-1 and downregulating NF-kappa B.

Automated summary

Sinapic acid has hepatoprotective effects against acute liver failure induced by LPS/D-GalN in rats by reducing inflammation and oxidative stress, and regulating Nrf2/HO-1 and NF-kappa B pathways.