Elevated citrate levels in non-alcoholic fatty liver disease: The potential of citrate to promote radical production

B. van de Wier*, J.M. Balk, G.R.M.M. Haenen, D. Giamouridis, J.A. Bakker, B.C. Bast, G.J.M. den Hartog, G.H. Koek, A. Bast

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Plasma citrate levels were found to be elevated in non-alcoholic fatty liver disease (NAFLD) patients. Cellular experiments indicated that increased citrate levels might originate from an excess of fatty acids. The impact of elevated citrate levels on oxidative stress was examined. It was found that citrate stimulated hydrogen peroxide induced intracellular oxidative stress in HepG2 cells. This was related to the promotion of iron mediated hydroxyl radical formation from hydrogen peroxide by citrate. The stimulating effect of citrate on the reactivity of iron promotes oxidative stress, a crucial process in the progression of NAFLD.

Original languageEnglish
Pages (from-to)2461-2466
Number of pages6
JournalFebs Letters
Volume587
Issue number15
DOIs
Publication statusPublished - 2 Aug 2013

Keywords

  • Citrate
  • Non-alcoholic fatty liver disease
  • Oxidative stress
  • Fenton reaction
  • Hydroxyl radical
  • Iron
  • MICROSOMAL LIPID-PEROXIDATION
  • HYDROXYL RADICALS
  • OXIDATIVE STRESS
  • IRON CHELATORS
  • CITRIC-ACID
  • STEATOHEPATITIS
  • COMPLEXES
  • FERRITIN
  • DAMAGE

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