Urinary 8-isoprostane

Fig. 65. Relationship between urinary 8-isoprostane and serum creatinine levels. In the initial phase, when the serum creatinine level was high, there was no increase in urinary 8-isoprostane. In the recovery phase, the urinary 8-isoprostane level increased...

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. 

Fig. 70. Exercise loading and urinary 8-iso-prostane levels. There were no marked differences in the changes in urinary 8-isoprostane between a patient with a history of ALPE and the control...

Barden, A, Beilin, LJ, Ritchie, J, Croft, KD, Walters, BN andMichaef CA (1996) Plasma and urinary 8-isoprostane as an indicator of lipid peroxidation in pieeclampsia and normal pregnancy. ClinSci (London), 91, 711-718. 

Neutrophil LO or urinary isoprostanes Anti-inflammatory LO inhibitors... 

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... 

Isoprostanes are the end breakdown products of lipid peroxidation, and urinary levels have been used to assess the level of oxidative stress. It is thought that oxidation of LDL is essential for the development of atherosclerosis and that HDL and other antioxidants work by antagonizing this oxidative stress. Urinary isoprostanes give one some summary assessment of this critical process. The most common ones measured are Fj-isoprostanes, but there are a large number of potential ones to measure. It does appear that they will eventually be helpful in assessing oxidative stress. 

Richelle, M, Tuiini, ME, Guidoux, R, Tavazzi, I, Metairon, S and Eay, LB (1999) Urinary isoprostane excretion is not confounded by the hpid content of diet. FEES Lett, 459, 259-262. 

Fowke JH, Morrow JD, Motley S, Bostick RM and Ness RM. 2006. Brassica vegetable consumption reduces urinary F2-isoprostane levels independent of micronutrient intake. Carcinogenesis 27(10) 2096-2102. 

At present, antioxidants are extensively studied as supplements for the treatment diabetic patients. Several clinical trials have been carried out with vitamin E. In 1991, Ceriello et al. [136] showed that supplementation of vitamin E to insulin-requiring diabetic patients reduced protein glycosylation without changing plasma glucose, probably due to the inhibition of the Maillard reaction. Then, Paolisso et al. [137] found that vitamin E decreased glucose level and improved insulin action in noninsulin-dependent diabetic patients. Recently, Jain et al. [138] showed that vitamin E supplementation increased glutathione level and diminished lipid peroxidation and HbAi level in erythrocytes of type 1 diabetic children. Similarly, Skyrme-Jones et al. [139] demonstrated that vitamin E supplementation improved endothelial vasodilator function in type 1 diabetic children supposedly due to the suppression of LDL oxidation. Devaraj et al. [140] used the urinary F2-isoprostane test for the estimate of LDL oxidation in type 2 diabetics. They also found that LDL oxidation decreased after vitamin E supplementation to patients. 

D, Dworski R, Kanai K, Taber D, Moore K, Oates JA, 23. Roberts LJ. Quantification of the major urinary metaboUte of 15-F2t-isoprostane (8-iso-PGF2alpha) by a stable isotope dilution mass spectrometric assay. Anal. Biochem. 1999 269 326. 

Milne GL, Gao L, Porta A, Zanoni G, Vidari G, Morrow JD. Identification of the major urinary metabolite of the highly reactive cyclopentenone isoprostane 15-A(2t)-isoprostane in vivo. J. Biol. Chem. 2005 280 25178. 

Morales CR, Terry ES, Zackert WE, Montine TJ and Morrow JD, Improved assay for the quantification of the major urinary metabolite of the isoprostane 15-F(2t)-Isoprostane (8-iso-PGF(2alpha)) by a stable isotope dilution mass spectrometric assay. Clin Chim Acta 314(1-2) 93-9. 2001. 

Nokami, J., Furukawa, A., Okuda, Y, Hazato, A., and Kurozumi. S., Palladium-catalyzed coupling reactions of bromobenzaldehydes with 3,4-di(tert-butylmethylsilyloxy)-l-alkene to (3,4-dihydroxy-alkenyl)benzaldehydes in the synthesis of lipoxin analogues, Tetrahedron Lett., 39, 1005, 1998. Adiyaman, M., Lawson, J.A., FitzGerald. G.A., and Rokach, J.. Synthesis and identification of the most abundant urinary type VI isoprostanes, Tetrahedron Lett., 39, 7039, 1998. 

In conclusion, a regular dietary intake of co-3 PUFA didn t have any influence on the susceptibility of LDL to copper-induced oxidation, including foods rich in co-3 PUFA reduced in vivo lipid peroxidation and hence urinary F2 isoprostane excretion [86],... 

Mori, T.A., Puddey, I.B., Burke, V., Croft, K.D., Dunstan, D.W., Rivera, J.H., and BeHin, L.J. (2000) Effect of cn3 Fatty Acids on Oxidative Stress in Humans GC-MS Measurements of Urinary F2-Isoprostane Excretion, Redox Report 5,45-46. 

Sasaki DM, Yuan Y, Gikas K, Kanai K, Taber D, Morrow JD, Roberts LJ, Callewaert DM. Enz5me immunoassays for 15-F2T isoprostane-M, an urinary biomarker for oxidant stress. Adv Exp Med Biol 2002 507 537-541. 

In view of the earlier identification of isoprostane-containing phosphatidylcholines (PCs) as indicators of oxidative stress (Morrow et al., 1992, 1994), the recent isolation and identification of a major urinary metabolite of p2 isoprostane 8-iso-PGF2a as 2,3-dinor-5,6-dihydro-8-iso-prostaglandin p2a (Roberts et al, 1996) is of special interest. The urinary metabolite of 8-iso-PGp2a was analysed by GC/NICI/MS after conversion to the PPB ester, TMS ether and catalytic hydrogenation. 

In a metabolic study in which tritium-labelled 8-iso-PGF2, (a major F -isoprostane) was intravenously administered to rabbits, the total radioactivity was found to disappear quickly from the circulation (Basu, 1998c). The plasma half-life of 8-iso-PGF in rabbits was found to be 1 min at the distribution phase. The terminal elimination phase half-life was about 4 min. Several polar P-oxidized metabolites were found in the plasma and were finally excreted efficiently into the urine. a-Tetranor-15-keto-13,14-dihydro-8-iso-PGF2 was identified as a major urinary metabolite in the rabbits, along with several other P-oxidized products. The metabolism of 8-iso-PGp2 j to a-tetranor-15-keto-... 

Most of the assays of isoprostanes to date have focused on assessing 8-iso-PGF levels in body fluids, since this is a major product of the total peroxidation process in vivo. When measuring the urinary metabolites of S-iso-PGF, the correct choice of the appropriate metabolite is important since the metabolic profile and appearance of the different metabolites vary between species (Roberts et al, 1996 Basu, 1998c Chiabrando et al, 1999). The tetranor metabolite of 8-iso-PGFj is the major urinary product in the rabbit, whereas the dinor metabolite is the dominant product in humans. 

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