title: Elevated citrate levels in non-alcoholic fatty liver disease: the potential of citrate to promote radical production.
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.
authors.affiliation: Department of Toxicology, Maastricht University, Maastricht, The Netherlands. b.vandewier@maastrichtuniversity.nl
authors.forename: Bregje
authors.initials: B
authors.lastname: van de Wier
authors.forename: Jiska M
authors.initials: JM
authors.lastname: Balk
authors.forename: Guido R M M
authors.initials: GR
authors.lastname: Haenen
authors.forename: Dimosthenis
authors.initials: D
authors.lastname: Giamouridis
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Bakker
authors.forename: Bertine C
authors.initials: BC
authors.lastname: Bast
authors.forename: Gertjan J M
authors.initials: GJ
authors.lastname: den Hartog
authors.forename: Ger H
authors.initials: GH
authors.lastname: Koek
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
mesh_terms: D000368:Aged; D019343:Citric Acid / Q000097:blood*; D005234:Fatty Liver / Q000097:blood*; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D018384:Oxidative Stress
chemical_list: D019343:Citric Acid; D006861:Hydrogen Peroxide
keywords: ()OH; 2,7-dichlorofluorescin diacetate; 2-deoxy-d-ribose; 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide; Citrate; DCFH-DA; DMPO; DPBS; Deoxyribose; Dulbecco’s phosphate buffered saline; ESR; Fe(2+); FeCl(3); FeSO(4); Fenton reaction; H(2)O(2); HepG2; Hydroxyl radical; Iron; NAFLD; NASH; Non-alcoholic fatty liver disease; Oxidative stress; ROS; electron spin resonance; ferric chloride; ferrous ion; ferrous sulphate; human hepatoma cell line; hydrogen peroxide; hydroxyl radical; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; reactive oxygen species