Hydrogen sulfide, a potential novel drug, attenuates concanavalin A-induced hepatitis

Drug Des Devel Ther. 2014 Sep 9:8:1277-86. doi: 10.2147/DDDT.S66573. eCollection 2014.

Abstract

Background: Hydrogen sulfide (H2S) is known to exert anti-inflammatory properties. Apoptosis and autophagy play important roles in concanavalin A (Con A)-induced acute hepatitis. The purpose of this study was to explore both the effect and mechanism of H2S on Con A-induced acute hepatitis.

Methods: BALB/c mice were randomized into sham group, Con A-injection group, and 14 μmol/kg of sodium hydrosulfide (NaHS, an H2S donor) pretreatment group.

Results: Aspartate aminotransferase, alanine aminotransferase, and pathological damage were significantly ameliorated by NaHS pretreatment. NaHS pretreatment significantly reduced the levels of interleukin-6 and tumor necrosis factor-α compared with those of the Con A group. The expression of Bcl-2, Bax, Beclin-1, and LC3-2, which play important roles in the apoptosis and autophagy pathways, were also clearly affected by NaHS. Furthermore, NaHS affected the p-mTOR and p-AKT.

Conclusion: H2S attenuates Con A-induced acute hepatitis by inhibiting apoptosis and autophagy, in part, through activation of the PtdIns3K-AKT1 signaling pathway.

Keywords: NaHS; PtdIns3K-AKT; apoptosis; autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Concanavalin A / administration & dosage
  • Concanavalin A / antagonists & inhibitors
  • Concanavalin A / pharmacology
  • Dose-Response Relationship, Drug
  • Hepatitis / drug therapy*
  • Hepatitis / metabolism
  • Hepatitis / pathology
  • Hydrogen Sulfide / administration & dosage
  • Hydrogen Sulfide / pharmacology*
  • Hydrogen Sulfide / therapeutic use*
  • Injections, Intravenous
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects

Substances

  • Concanavalin A
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Hydrogen Sulfide