Markers isoprostanes

The determination of F2-isoprostanes, oxidation products of arachidonic acid, has been proposed as a more reliable index of oxidative stress in vivo, overcoming many of the methodological problems associated with other markers. The isoprostanes have emerged as a most effective method of quantifying the potential of antioxidants to inhibit lipid peroxidation. However, one drawback of this method is that quantification of F2-iP requires sophisticated techniques, in particular GC/MS and HPLC/MS... 

Although the acute vasodilator effects, as shown in in vitro studies (see above), may participate in the antihypertensive effects, the reduced blood pressure persisted even 42-48 h after the last administration of quercetin, when the plasma quercetin concentration and its metabolites fell bellow 25% of the peak post-administration levels [43]. Furthermore, the antihypertensive effects of quercetin did not appear to be related to its antioxidant properties since quercetin did not lower the urinary isoprostane F20 excretion, a prostaglandin-like compound produced in a non enzymatic reaction of arachidonic acid in membrane lipids and superoxide, which is currently used as a reliable marker of oxidative stress. The mechanisms involved in the antihypertensive effects and protection from organ damage... 

Greco A, Minghetti L, Levi G. 2000. Isoprostanes, novel markers of oxidative injury, help understanding the pathogenesis of neurodegenerative diseases. Neurochem Res 25 1357-1364. 

Shoskes, D. A., Webster, R., and Shahed, A., Oxidant stress in cadaveric and living kidney donors as markers of renal injury Utility of total antioxidant capacity and isoprostane levels in urine. Transplant. Proc. 32, 804-805 (2000). 

Montuschi R Barnes PJ, Roberts LJ. Isoprostanes markers and mediators of oxidative stress. FASEB 2004 I 8 1791 -1 800,... 

We selected one renal hypouricemia patient with a history of ALPE and one healthy adult (control) without a history of ALPE, and measured creatinine clearance, FEUA, and oxidative stress markers (urinary 8-isoprostane and NOx) after anaerobic and aerobic exercise load tests (a 400-m race, 16 min on a treadmill, Bruce method, 13.5metabolic equivalents (METs)) (Fig. 67). In the hypouricemia patient, (a) exercise reduced creatinine clearance (Fig. 68), (b) FEUA increased 5h after the exercise load test (Fig. 69), (c) the urinary 8-isoprostane level increased slightly 6-25h after the exercise load test, although there were no marked differences compared with the control values (Fig. 70), and (d) the urinary NOx level increased 2 and 5h after the exercise load test (Fig. 71). Thus, we found that exercise reduced creatinine clearance in the renal hypouricemia patient with a history of ALPE, but there was no marked influence of oxidative stress. 

Roberts L Jr, Morrow JD. lYoducts of the isoprostane pathway unique bioactive compounds and markers of lipid peroxidation. Cell Mol. Life Sci. 2002 59 808. 

Patrono C, Fitzgerald GA. Isoprostanes potential markers of oxidant stress in atherothrombotic disease. Arterioscler. Thromb. Vase. Biol. 

The assays most widely employed are the measurement of thiobarbituric acid-reactive species (TBARS) and the formation of conjugated dienes, markers of lipid peroxidation [31-33] the determination of advanced oxidation protein products (AOPP), a marker of protein oxidation, and of advanced glycation end-products (AGE) [34-37] the measurement of erythrocyte antioxidant potential [38]. Of particular importance is the isoprostanes determination, since these compounds are formed by the free radical catalysed peroxidation of arachidonic acid, which is independent of the cyclooxygenase enzyme, giving rise to stable compounds, measurable in urine [39]. As recently assessed in a Workshop on markers of oxidative damage and antioxidant protection [40], currently available methods for the determination of antioxidant and redox status are not yet generally suitable for routine clinical applications, essentially for the lack of standardized tests. 

In HD, one study reported no increase in 8-hydroxy-2 -deoxyguanosine or other markers of DNA oxidation, and no change in lipid peroxidation. In contrast, other studies have shown increases in the lipid peroxidation markers F2-isoprostane and MDA in HD (Mariani et al., 2005). 

Another group of prostanoids known as isoprostanes are formed from AA and other fatty acids by nonenzymatic autooxidation. The side chains of isoprostanes are primarily in the trans orientation. Somewhat surprisingly, isoprostanes and their metabolites are found in greater quantities in urine than metabolites of prostanoids formed enzymatically via the COX. Particularly in pathological conditions that support autooxidation (e.g., CCI4 toxicity), isoprostanes are produced in abundance, and they may be general markers for oxidant stress [2]. 

Fig. 6. Structures of two arachidonic acid derivatives proposed to play important roles in thrombosis and atherogenesis. Thromboxane Aj is a potent inducer of platelet aggregation that contributes to acute thrombosis in advanced atherosclerosis in vivo. The isoprostane S-iso-PGFj is being investigated as a marker of oxidative stress in atherosclerosis and may also have direct atherogenic effects on platelets and smooth muscle cells.

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