GSH protects against oxidative stress and toxicity in VL-17A cells exposed to high glucose

Eur J Nutr. 2015 Mar;54(2):223-34. doi: 10.1007/s00394-014-0703-2. Epub 2014 Apr 23.

Abstract

Purpose: The deficiency of glutathione (GSH) has been linked to several diseases. The study investigated the role of GSH as a protective factor against hyperglycemia-mediated injury in VL-17A cells treated with 50 mM glucose.

Methods: The cell viability and different oxidative stress parameters including glyoxalase I activity were measured.

Results: GSH supplementation with 2 mM N-acetyl cysteine (NAC) or 0.1 mM ursodeoxycholic acid (UDCA) increased the viability, GSH level and the GSH-dependent glyoxalase I activity in 50 mM glucose-treated VL-17A cells. Further, pretreatment of 50 mM glucose-treated VL-17A cells with NAC or UDCA decreased oxidative stress (levels of reactive oxygen species and protein carbonylation), apoptosis (caspase 3 activity and annexin V-propidium iodide positive cells) and glutathionylated protein formation, a measure of oxidative stress. GSH depletion with 0.4 mM buthionine sulfoximine (BSO) or 1 mM diethyl maleate (DEM) potentiated the decrease in viability, glyoxalase I activity and increase in oxidative stress and apoptosis, with decreased GSH levels in 50 mM glucose-treated VL-17A cells.

Conclusion: Thus, changes in GSH levels with exogenous agents such as NAC, UDCA, BSO or DEM modulate hyperglycemia-mediated injury in a cell model of VL-17A liver cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / metabolism
  • Alcohol Dehydrogenase / genetics
  • Alcohol Dehydrogenase / metabolism
  • Antimetabolites / pharmacology
  • Antioxidants / pharmacology
  • Apoptosis* / drug effects
  • Buthionine Sulfoximine / pharmacology
  • Cell Survival / drug effects
  • Clone Cells
  • Cytochrome P-450 CYP2E1 / genetics
  • Cytochrome P-450 CYP2E1 / metabolism
  • Glucose / adverse effects
  • Glutathione / antagonists & inhibitors
  • Glutathione / metabolism*
  • Hep G2 Cells
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Humans
  • Hyperglycemia / metabolism*
  • Lactoylglutathione Lyase / metabolism
  • Maleates / pharmacology
  • Oxidative Stress* / drug effects
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Recombinant Proteins / metabolism
  • Ursodeoxycholic Acid / pharmacology

Substances

  • Antimetabolites
  • Antioxidants
  • Maleates
  • Reactive Oxygen Species
  • Recombinant Proteins
  • Buthionine Sulfoximine
  • Ursodeoxycholic Acid
  • Alcohol Dehydrogenase
  • Cytochrome P-450 CYP2E1
  • GLO1 protein, human
  • Lactoylglutathione Lyase
  • diethyl maleate
  • Glutathione
  • Glucose
  • Acetylcysteine