title: Systematic review of ophthalmate as a novel biomarker of hepatic glutathione depletion.
abstract: BACKGROUND
  Sustainability of hepatic glutathione (GSH) homeostasis is an important cellular defense against oxidative stress. Therefore, knowledge of liver GSH status is important. However, measurement of plasma GSH and tissue is difficult due to its instability. Alternatively, ophthalmate (OPH), an endogenous tripeptide analog of GSH, has been suggested as a potential indicator to assess GSH depletion.
  
  
  OBJECTIVE
  To provide an overview of present knowledge with respect to the usefulness of OPH as a biomarker for oxidative stress and hepatic GSH homeostasis.
  
  
  METHODS
  A systematic, computerized search combined with a cross-reference search of the literature described in PubMed (January 1975 to January 2012) was conducted, key words: 'ophthalmate' and 'ophthalmic acid'.
  
  
  RESULTS
  Twenty-two articles were included. Hepatic OPH levels increase inversely proportional to a drop in hepatic GSH in mice with paracetamol (PCM) induced hepatotoxicity. Little is known about the stability of OPH in human plasma. To measure the very low physiological concentrations of plasma OPH, liquid chromatography-mass spectrometry techniques can be employed. OPH synthesis can be measured in humans, using stable isotope labeling with a deuterated water ((2)H2O) load.
  
  
  CONCLUSIONS
  OPH may be a promising biomarker to indicate hepatic glutathione depletion, but the suggested biological pathways need further unraveling.
authors.affiliation: Department of Surgery, Maastricht University Medical Center & Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. S.dello@maastrichtuniversity.nl
authors.forename: Simon A W G
authors.initials: SA
authors.lastname: Dello
authors.forename: Evelien P J G
authors.initials: EP
authors.lastname: Neis
authors.forename: Mechteld C
authors.initials: MC
authors.lastname: de Jong
authors.forename: Hans M H
authors.initials: HM
authors.lastname: van Eijk
authors.forename: Cécile H
authors.initials: CH
authors.lastname: Kicken
authors.forename: Steven W M
authors.initials: SW
authors.lastname: Olde Damink
authors.forename: Cornelis H C
authors.initials: CH
authors.lastname: Dejong
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002853:Chromatography, Liquid; D017666:Deuterium Oxide / Q000032:analysis; D005978:Glutathione / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D009842:Oligopeptides / Q000097:blood*; D018384:Oxidative Stress
chemical_list: D015415:Biomarkers; D009842:Oligopeptides; D000082:Acetaminophen; C016632:ophthalmic acid; D005978:Glutathione; D017666:Deuterium Oxide