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

• Published in: FEBS letters Vol. 587; no. 15; pp. 2461 - 2466
• Main Authors: van de Wier, Bregje, Balk, Jiska M., Haenen, Guido R.M.M., Giamouridis, Dimosthenis, Bakker, Jaap A., Bast, Bertine C., den Hartog, Gertjan J.M., Koek, Ger H., Bast, Aalt
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 02-08-2013
• Subjects: 2,7-dichlorofluorescin diacetate; 2-deoxy-d-ribose; 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide; Aged; Citrate; Citric Acid - blood; DCFH-DA; Deoxyribose; DMPO; DPBS; Dulbecco's phosphate buffered saline; electron spin resonance; ESR; Fatty Liver - blood; Fe2; FeCl3; Female; Fenton reaction; ferric chloride; ferrous ion; ferrous sulphate; FeSO4; H2O2; Hep G2 Cells; HepG2; human hepatoma cell line; Humans; hydrogen peroxide; Hydrogen Peroxide - metabolism; Hydroxyl radical; Iron; Male; Middle Aged; NAFLD; NASH; Non-alcoholic Fatty Liver Disease; non-alcoholic steatohepatitis; OH; Oxidative Stress; reactive oxygen species; ROS; Oxidative stress; NAFLD; FeCl3; ESR; Deoxyribose; DMPO; Citrate; Iron; NASH; H2O2; FeSO4; DCFH-DA; Fe2; ROS; HepG2; OH; Fenton reaction; Non-alcoholic fatty liver disease; DPBS; Hydroxyl radical; 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide; HO; FeCl; 2-deoxy-d-ribose; electron spin resonance; Fe(2+); 2,7-dichlorofluorescin diacetate; reactive oxygen species; FeSO; ferric chloride; human hepatoma cell line; ferrous ion; hydrogen peroxide; ferrous sulphate; Dulbecco’s phosphate buffered saline; non-alcoholic steatohepatitis
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2013.06.019

•Citrate levels are elevated in patients with non-alcoholic fatty liver disease.•Intracellular citrate levels are elevated upon exposure to an excess of fatty acids.•Citrate promotes iron mediated radical formation in in vitro experiments.
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.