Biomarkers Of Oxidative Stress Study

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We now have new findings from measurement of oxidative stress in two additional experimental animal models of oxidative stress: 90-day cumene hydroperoxde dermal exposure and LPS treatment of minipigs. The time and dose-dependent effects of these oxidative insults on plasma and urine concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA) and isoprostanes were investigated with both old and new techniques. Measures of oxidative products of proteins (protein carbonyls, methionine sulfoxidation, and tyrosine oxidation products) and of DNA (strand breaks, 8-OHdG, and M1G) were carried out as well. In addition, the time- and dose-dependent effects of the two exposures on plasma levels of alpha-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 a decrease of plasma antioxidants. Previous acute exposure to CCl4 and ozone 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. 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 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.