Published online Feb 21, 2021. doi: 10.3748/wjg.v27.i7.592
Peer-review started: October 26, 2020
First decision: November 25, 2020
Revised: November 30, 2020
Accepted: January 21, 2021
Article in press: January 21, 2021
Published online: February 21, 2021
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.
In the current study, the hepatoprotective effects of SA against lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver failure (ALF) in rats were studied.
In the current study, the hepatoprotective effects of SA against LPS/D-GalN-induced acute liver failure (ALF) in rats were studied.
Experimental ALF was induced with an intraperitoneal (i.p.) administration of 8 μg LPS and 800 mg/kg D-GalN in normal saline. SA was administered orally once daily starting 7 d before LPS/D-GalN treatment.
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-κB) activation and levels of inflammatory cytokines (tumor necrosis factor-α and interleukin 6). Also, SA increased the activity of the nuclear factor erythroid-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway.
In conclusion, SA offers significant protection against LPS/D-GalN-induced ALF in rats by upregulating Nrf2/HO-1 and downregulating NF-κB.
The amolearation of LPS/D-GalN-induced fulminant hepatitis through NRF2/HO-1 activation have been previously documented. However, the hepatoprotective effects of SA in LPS/D-GalN-induced fulminant hepatitis has not been previously investigated. To identify the detailed mechanisms of action for SA, we tested its antioxidant and anti-inflammatory activities in a rat model of LPS/D-GalN-induced fulminant hepatitis. Thus, the purpose of the current study was to explore the underlying hepatoprotective mechanism of SA against LPS/D-GalN-induced ALF in rats. We also aimed to identify its effects on ROS production, inflammation and apoptosis and the roles of Nrf2/HO-1 and NF-κB pathways.