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

World J Gastroenterol. 2021 Feb 21;27(7):592-608. doi: 10.3748/wjg.v27.i7.592.

Abstract

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 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.

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-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.

Conclusion: In conclusion, SA offers significant protection against LPS/D-GalN-induced ALF in rats by upregulating Nrf2/HO-1 and downregulating NF-κB.

Keywords: Antioxidant; D-galactosamine/lipopolysaccharide; Fulminant hepatitis; Nuclear factor erythroid-related factor 2/heme oxygenase-1 pathways; Oxidative stress; Sinapic acid.

MeSH terms

  • Animals
  • Chemical and Drug Induced Liver Injury* / drug therapy
  • Chemical and Drug Induced Liver Injury* / etiology
  • Chemical and Drug Induced Liver Injury* / prevention & control
  • Coumaric Acids
  • GATA1 Transcription Factor
  • Galactosamine / toxicity
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Lipopolysaccharides / toxicity
  • Liver
  • Massive Hepatic Necrosis*
  • NF-kappa B
  • Rats
  • Tumor Necrosis Factor-alpha

Substances

  • Coumaric Acids
  • GATA1 Transcription Factor
  • Lipopolysaccharides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • sinapinic acid
  • Galactosamine
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1