Oxidation products of lipids in plasma and urine of rats were measured as part of a comprehensive, multilaboratory validation study searching for non-invasive biomarkers of oxidative stress. This is the second report of the nationwide Biomarkers of Oxidative Stress Study (BOSS) using the 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 ip) effects of CCl4 on concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA),isoprostanes, protein carbonyls, methionine sulfoxidation, tyrosine products, 8-hydroxy-2'deoxyguanosine(8-OHdG), leucocyte DNA-MDA adducts and DNA strand breaks were investigated with different techniques to determine whether the oxidative effects of CCl4 would result in increased generation of these oxidation products.Plasma concentrations of MDA and isoprostanes (measured by GC/MS) and urinary concentrations of isoprostanes (measured with an immunoassay) were increased in CCl4 treated rats in a time- and dose-dependent manner. All other products were not changed by CCl4 or showed only high-dose and/or single time point effects. It is concluded that measurements of MDA and isoprostanes concentrations in plasma and urinary isoprostanes are promising candidates for general biomarkers of oxidative stress. Measures of oxidation products of proteins and DNA were not reliable biomarkers for radical damage induced by CCl4.
