The acute exposure to CCl4, ozone, 90-day cumene hydroperoxide exposure were used as diverse experimental models of oxidative stress. It was found that 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. In the ozone exposure model, however, plasma concentrations of MDA and isoprostanes (measured by GC/MS) were not changed whereas urinary concentrations of isoprostanes (measured with an immunoassay) were increased. Measures of oxidation products of proteins (protein carbonyls, methionine sulfoxidation, tyrosine oxidation products) and DNA (strand breaks, 8-OHdG, M1G) were not changed in a time-and dose-dependent manner by CCl4 and ozone. There were no changes in the lipid peroxidation, oxidation of proteins and DN A in rats exposed for 90 days to cumene hydroperoxide.? ? In addition, the time- and dose-dependent effects of all three exposures on plasma levels of various antioxidants- of alfa-tocopherol, coenzyme Q (CoQ), ascorbic acid, glutathione (GSH and GSSG), uric acid and total antioxidant capacity were investigated to determine whether the oxidative effects of diverse insults would result in decrease of these antioxidants. ? ? It is concluded that measurements of free radical mediated lipid peroxidation products - MDA and isoprostanes concentrations in plasma (by GC/MS) and urinary isoprostanes (by immunoassay or GC/MS) are promising candidates for general biomarkers of oxidative stress. The ratio of GSH to GSSG generally declined with CCl4 treatment and the significant decrease in this ratio at 2h in both dose groups was identified as an early marker of oxidative stress. It is concluded that ascorbic acid concentration measured in blood plasma was an early reliable biomarker for radical damage induced by ozone exposure. In the rat model of 90-day cumene hydroperoxide exposure no changes in various plasma antioxidant levels were found. ? ? The pattern of oxidative stress biomarkers seen in these three exposures will offer insight into the specificity and sensitivity of the markers and will provide evidence that a given product of oxidation may be a marker for some type of oxidative stress but not others.
