Systematic review of ophthalmate as a novel biomarker of hepatic glutathione depletion

• Published in: Clinical nutrition (Edinburgh, Scotland) Vol. 32; no. 3; pp. 325 - 330
• Main Authors: Dello, Simon A.W.G, Neis, Evelien P.J.G, de Jong, Mechteld C, van Eijk, Hans M.H, Kicken, Cécile H, Olde Damink, Steven W.M, Dejong, Cornelis H.C
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-06-2013; Elsevier
• Subjects: Acetaminophen - adverse effects; Animals; Biological and medical sciences; biomarkers; Biomarkers - blood; Chromatography, Liquid; Deuterium Oxide - analysis; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gastroenterology and Hepatology; Glutathione; Glutathione - blood; Glutathione - metabolism; Hepatotoxicity; homeostasis; Humans; isotope labeling; LC–MS/MS; liquid chromatography; liver; Liver - metabolism; Mass Spectrometry; Mice; Oligopeptides - blood; Ophthalmate; Oxidative Stress; stable isotopes; systematic review; Vertebrates: anatomy and physiology, studies on body, several organs or systems; GSSG; OPH; LC–MS; GS; LC–MS/MS; glutathione-synthetase; liquid chromatography tandem mass spectrometry; 2AB; reduced glutathione; glutamyl-cysteine-synthetase; Ophthalmate; GCS; ROS; reactive oxygen species; glutathione disulfide (oxidized glutathione); NAPQI; N-acetyl-p-benzoquinone imine; Hepatotoxicity; GSH; Glutathione; 2-aminobutyrate; Depletion; Digestive system; Liver; Evidence-based practice; Biological marker; Metabolic diseases; Systematic review; Evidence-based medicine
• ISSN: 0261-5614; 1532-1983
• DOI: 10.1016/j.clnu.2012.10.008

Summary 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. Aim 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 H2 O) load. Conclusion OPH may be a promising biomarker to indicate hepatic glutathione depletion, but the suggested biological pathways need further unraveling.