Alpha-lipoic acid protects mice against concanavalin A-induced hepatitis by modulating cytokine secretion and reducing reactive oxygen species generation

Int Immunopharmacol. 2016 Jun;35:53-60. doi: 10.1016/j.intimp.2016.03.023. Epub 2016 Mar 25.

Abstract

Background: Alpha-lipoic acid (α-LA), which exits in almost all types of prokaryotic and eukaryotic cells, is a key regulator of energy metabolism in mitochondria. This study was designed to explore the protective effect of α-LA against concanavalin A (Con A)-induced hepatitis in mice and explore the potential mechanism.

Methods: Acute autoimmune hepatitis was induced by intravenous (IV) injection of Con A (15mg/kg) in C57BL/6 mice. α-LA (100mg/kg) was administered four days before Con A injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and histopathological change of the liver tissue were measured. Serum cytokine TNF-α, IL-6, IFN-γ and IL-10 were detected by ELISA. The mRNA levels of these inflammatory cytokines in the liver were detected by RT-PCR. Malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and reduced/oxidized glutathione (GSH/GSSG) in liver were determined using commercial kits. Phosphorylated NF-κB p65, IκBα and phosphorylated MAPK were measured by Western blot.

Results: Con A injection induced severe immune responses and extensive hepatocellular apoptosis within 12h. Pretreatment of α-LA markedly reduced the serum ALT and AST activity and the increase of plasma TNF-α, IL-6, IFN-γ and IL-10. In addition, α-LA pretreatment decreased the tissue MPO activity and lipid peroxidation, but increased SOD and GSH levels. α-LA inhibited the phosphorylation of NF-κB p65, IκBα and JNK.

Conclusion: Pretreatment of α-LA markedly attenuated Con A-induced hepatitis by modulating cytokine secretion and reducing reactive oxygen species generation.

Keywords: Alpha-lipoic acid; Concanavalin A-induced hepatitis; Reactive oxygen species.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Concanavalin A / toxicity
  • Cytokines / blood
  • Cytokines / genetics
  • Inflammation Mediators / blood
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Peroxidase / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Thioctic Acid / therapeutic use*

Substances

  • Cytokines
  • Inflammation Mediators
  • NF-kappa B
  • Reactive Oxygen Species
  • Concanavalin A
  • Thioctic Acid
  • Peroxidase
  • Aspartate Aminotransferases
  • Alanine Transaminase