title: Biomarkers of oxidative stress study VI. Endogenous plasma antioxidants fail as useful biomarkers of endotoxin-induced oxidative stress.
abstract: This is the newest report in a series of publications aiming to identify a blood-based antioxidant biomarker that could serve as an in vivo indicator of oxidative stress. The goal of the study was to test whether acutely exposing Göttingen mini pigs to the endotoxin lipopolysaccharide (LPS) results in a loss of antioxidants from plasma. We set as a criterion that a significant effect should be measured in plasma and seen at both doses and at more than one time point. Animals were injected with two doses of LPS at 2.5 and 5 µg/kg iv. Control plasma was collected from each animal before the LPS injection. After the LPS injection, plasma samples were collected at 2, 16, 48, and 72 h. Compared with the controls at the same time point, statistically significant losses were not found for either dose at multiple time points in any of the following potential markers: ascorbic acid, tocopherols (α, δ, γ), ratios of GSH/GSSG and cysteine/cystine, mixed disulfides, and total antioxidant capacity. However, uric acid, total GSH, and total Cys were significantly increased, probably because LPS had a harmful effect on the liver. The leakage of substances from damaged cells into the plasma may have increased plasma antioxidant concentrations, making changes difficult to interpret. Although this study used a mini-pig animal model of LPS-induced oxidative stress, it confirmed our previous findings in different rat models that measurement of antioxidants in plasma is not useful for the assessment of oxidative damage in vivo.
authors.affiliation: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Electronic address: Kadiiska@niehs.nih.gov.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Kadiiska
authors.affiliation: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Shyamal
authors.initials: S
authors.lastname: Peddada
authors.affiliation: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Herbert
authors.affiliation: Oxidative Stress and Inflammation, Department of Public Health and Caring Sciences, Faculty of Medicine, Uppsala University, Uppsala, Sweden.
authors.forename: Samar
authors.initials: S
authors.lastname: Basu
authors.affiliation: Department of Pathology, University of Toledo Medical Center, Toledo, OH 43614, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hensley
authors.affiliation: Department of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.affiliation: U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Hatch
authors.affiliation: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mason
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003545:Cysteine / Q000097:blood; D003553:Cystine / Q000097:blood; D004220:Disulfides / Q000097:blood; D005978:Glutathione / Q000097:blood; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis / Q000473:pathology; D007275:Injections, Intravenous; D008070:Lipopolysaccharides; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D024505:Tocopherols / Q000097:blood; D014527:Uric Acid / Q000097:blood
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D004220:Disulfides; D008070:Lipopolysaccharides; D014527:Uric Acid; D003553:Cystine; D005978:Glutathione; D003545:Cysteine; D001205:Ascorbic Acid; D024505:Tocopherols
keywords: Biomarkers; Free radicals; LPS; Mini-pig model; Oxidative stress; Plasma antioxidants