Caloric restriction mimetic 2-deoxyglucose alleviated lethal liver injury induced by lipopolysaccharide/D-galactosamine in mice

Biochem Biophys Res Commun. 2015 Apr 10;459(3):541-6. doi: 10.1016/j.bbrc.2015.02.145. Epub 2015 Mar 5.

Abstract

The glycolytic inhibitor 2-deoxyglucose (2-DG) is a calorie restriction (CR) mimetic produces CR-like beneficial effects in both acute and chronic pathological processes, but whether 2-DG is also helpful in critical and life-threatening situation is not known. In the present study, the potential benefits of 2-DG in lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced lethal liver injury were investigated. The results indicated that treatment with 2-DG suppressed the elevation of plasma aminotransferases, alleviated the histopathological abnormalities and improved the survival rate of LPS/D-Gal-exposed mice. Treatment with 2-DG also suppressed the production of pro-apoptotic cytokine TNF-α, the phosphorylation of JNK, the activation of caspase cascade and the count of TUNEL-positive apoptotic hepatocytes. These data suggested that the CR mimetic 2-DG could also provide beneficial effects in lethal pathological process such as LPS/D-Gal-induced fulminant liver injury.

Keywords: 2-Deoxyglucose; Calorie restriction mimetic; Lipopolysaccharide; Liver injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Apoptosis / drug effects
  • Aspartate Aminotransferases / blood
  • Biomimetics
  • Caloric Restriction
  • Caspases / metabolism
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Deoxyglucose / administration & dosage
  • Deoxyglucose / pharmacology*
  • Galactosamine / toxicity
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Lipopolysaccharides / toxicity
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Galactosamine
  • Deoxyglucose
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Caspases