Methyl 3,4-dihydroxybenzoate protects against d-galN/LPS-induced acute liver injury by inhibiting inflammation and apoptosis in mice

J Pharm Pharmacol. 2019 Jul;71(7):1082-1088. doi: 10.1111/jphp.13091. Epub 2019 Apr 29.

Abstract

Objectives: Aimed to investigate the effect and mechanism of methyl 3,4-dihydroxybenzoate (MDHB) on d-galactosamine/lipopolysaccharide (d-galN/LPS)-induced acute liver failure (ALF).

Methods: Confirmed the hepatoprotective effect and hepatotoxicity of MDHB by histopathological examination (HE) and examination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST); the expression of serum tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) was detected by ELISA; transcription levels of TNF-α, IL-1β, IL-6 and Toll-like receptor 4 (TLR4) were detected by qRT-PCR; and phosphorylation levels of p38 and p65 were analysed by Western blot.

Results: Histopathological examination and examination of ALT and AST confirmed that MDHB is a low toxicity drug that can resist d-galN/LPS-induced ALF; MDHB can effectively reduce high transcription and expression of TNF-α, IL-1β, IL-6 and TLR4 in d-galN/LPS-induced ALF; and Western blot showed that MDHB could down-regulate the expression of bax, up-regulate the expression of bcl-xl and bcl-2, and inhibit the phosphorylation of p38 and p65.

Conclusions: Methyl 3,4-dihydroxybenzoate can effectively resist d-galN/LPS-induced acute liver failure, which is related to the inhibition of inflammation and apoptosis.

Keywords: NF-kappa B; inflammation; lipopolysaccharide/d-galactosamine; liver injury; methyl 3,4-dihydroxybenzoate.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Apoptosis / drug effects*
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Galactosamine / pharmacology
  • Hydroxybenzoates / pharmacology*
  • Inflammation / drug therapy*
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / pharmacology
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • NF-kappa B p50 Subunit / metabolism
  • RNA, Messenger / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-Associated Death Protein / metabolism
  • bcl-X Protein / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Bcl2l1 protein, mouse
  • Hydroxybenzoates
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B p50 Subunit
  • RNA, Messenger
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • bcl-Associated Death Protein
  • bcl-X Protein
  • Nfkb1 protein, mouse
  • Galactosamine
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • p38 Mitogen-Activated Protein Kinases
  • methyl 3,4-dihydroxybenzoate