title: Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning?
abstract: Oxidation products of lipids, proteins, and DNA in the blood, plasma, and urine of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. This article is the second report of the nationwide Biomarkers of Oxidative Stress Study using acute CCl4 poisoning as a rodent model for oxidative stress. The time-dependent (2, 7, and 16 h) and dose-dependent (120 and 1200 mg/kg i.p.) effects of CCl4 on concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA), isoprostanes, protein carbonyls, methionine sulfoxidation, tyrosine products, 8-hydroxy-2'-deoxyguanosine (8-OHdG), leukocyte DNA-MDA adducts, and DNA-strand breaks were investigated to determine whether the oxidative effects of CCl4 would result in increased generation of these oxidation products. Plasma concentrations of MDA and isoprostanes (both measured by GC-MS) and urinary concentrations of isoprostanes (measured with an immunoassay or LC/MS/MS) were increased in both low-dose and high-dose CCl4-treated rats at more than one time point. The other urinary markers (MDA and 8-OHdG) showed significant elevations with treatment under three of the four conditions tested. It is concluded that measurements of MDA and isoprostanes in plasma and urine as well as 8-OHdG in urine are potential candidates for general biomarkers of oxidative stress. All other products were not changed by CCl4 or showed fewer significant effects.
authors.affiliation: Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, MD F0-02, Research Triangle Park, NC 27709, USA. Kadiiska@niehs.nih.gov
authors.forename: M B
authors.initials: MB
authors.lastname: Kadiiska
authors.forename: B C
authors.initials: BC
authors.lastname: Gladen
authors.forename: D D
authors.initials: DD
authors.lastname: Baird
authors.forename: D
authors.initials: D
authors.lastname: Germolec
authors.forename: L B
authors.initials: LB
authors.lastname: Graham
authors.forename: C E
authors.initials: CE
authors.lastname: Parker
authors.forename: A
authors.initials: A
authors.lastname: Nyska
authors.forename: J T
authors.initials: JT
authors.lastname: Wachsman
authors.forename: B N
authors.initials: BN
authors.lastname: Ames
authors.forename: S
authors.initials: S
authors.lastname: Basu
authors.forename: N
authors.initials: N
authors.lastname: Brot
authors.forename: G A
authors.initials: GA
authors.lastname: Fitzgerald
authors.forename: R A
authors.initials: RA
authors.lastname: Floyd
authors.forename: M
authors.initials: M
authors.lastname: George
authors.forename: J W
authors.initials: JW
authors.lastname: Heinecke
authors.forename: G E
authors.initials: GE
authors.lastname: Hatch
authors.forename: K
authors.initials: K
authors.lastname: Hensley
authors.forename: J A
authors.initials: JA
authors.lastname: Lawson
authors.forename: L J
authors.initials: LJ
authors.lastname: Marnett
authors.forename: J D
authors.initials: JD
authors.lastname: Morrow
authors.forename: D M
authors.initials: DM
authors.lastname: Murray
authors.forename: J
authors.initials: J
authors.lastname: Plastaras
authors.forename: L J
authors.initials: LJ
authors.lastname: Roberts
authors.forename: J
authors.initials: J
authors.lastname: Rokach
authors.forename: M K
authors.initials: MK
authors.lastname: Shigenaga
authors.forename: R S
authors.initials: RS
authors.lastname: Sohal
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: R R
authors.initials: RR
authors.lastname: Tice
authors.forename: D H
authors.initials: DH
authors.lastname: Van Thiel
authors.forename: D
authors.initials: D
authors.lastname: Wellner
authors.forename: P B
authors.initials: PB
authors.lastname: Walter
authors.forename: K B
authors.initials: KB
authors.lastname: Tomer
authors.forename: R P
authors.initials: RP
authors.lastname: Mason
authors.forename: J C
authors.initials: JC
authors.lastname: Barrett
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D020552:Comet Assay; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005609:Free Radicals; D008401:Gas Chromatography-Mass Spectrometry; D006861:Hydrogen Peroxide / Q000378:metabolism; D007118:Immunoassay; D015151:Immunoblotting; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000494:pharmacology; D008715:Methionine / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013053:Spectrophotometry; D017392:Thiobarbituric Acid Reactive Substances; D013997:Time Factors; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
chemical_list: D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D014443:Tyrosine; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D008715:Methionine; D006861:Hydrogen Peroxide; D002251:Carbon Tetrachloride; D003849:Deoxyguanosine; D010100:Oxygen