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      8-Iso-Prostaglandin F as a Useful Clinical Biomarker of Oxidative Stress in ESRD Patients

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          Abstract

          Background/Aims: Chronic renal failure is associated with elevated indices of oxidative stress. We tested the hypothesis that the in vivo formation of the F<sub>2</sub>-isoprostane (8-iso-prostaglandin PGF<sub>2α</sub>), a bioactive product of arachidonic acid peroxidation, is enhanced in end-stage renal disease (ESRD) patients receiving hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). Methods: Plasma samples were obtained from 35 HD patients, 30 CAPD patients and 30 age- and sex-matched healthy subjects for measurement of immunoreactive 8-iso-PGF<sub>2α</sub>. Results: Plasma 8-iso-PGF<sub>2α</sub> levels were significantly higher (p < 0.001) in HD and CAPD patients (346.3 ± 132.4 pg/ml; range 49.8–870) than in age-matched control subjects (150.9 ± 61.6 pg/ml; range 33.5–235). In addition, we also found that 8-iso-PGF<sub>2α</sub> concentration was significantly (p = 0.007) higher in HD patients (389.8 ± 148.3 pg/ml) than in CAPD patients (254.3 ± 76.6 pg/ml). Plasma 8-iso-PGF<sub>2α</sub> concentration was linearly correlated with serum haptoglobin, C-reactive protein (CRP) and plasma MDA (r = 0.58, p = 0.003; r = 0.29, p < 0.05 and r = 0.38, p < 0.05 respectively). On the other hand, plasma 8-iso-PGF<sub>2α</sub> levels were inversely associated with serum albumin and total cholesterol (r = –0.31 and r = –0.28, respectively; p < 0.05). Conclusions: We conclude that ESRD on both HD and CAPD is associated with increased formation of F<sub>2</sub>-isoprostanes, a correlate of enhanced lipid peroxidation. We also found that plasma 8-iso-PGF<sub>2α</sub> was casually related to some acute phase reactant proteins such as serum CRP, albumin and haptoglobin. This may provide an important biochemical link between lipid peroxidation, inflammation and accelerated atherosclerosis in the uremic milieu.

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          Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. Smoking as a cause of oxidative damage.

          It has been hypothesized that the pathogenesis of diseases induced by cigarette smoking involves oxidative damage by free radicals. However, definitive evidence that smoking causes the oxidative modification of target molecules in vivo is lacking. We conducted a study to determine whether the production of F2-isoprostanes, which are novel products of lipid peroxidation, is enhanced in persons who smoke. We measured the levels of free F2-isoprostanes in plasma, the levels of F2-isoprostanes esterified to plasma lipids, and the urinary excretion of metabolites of F2-isoprostanes in 10 smokers and 10 nonsmokers matched for age and sex. The short-term effects of smoking (three cigarettes smoked over 30 minutes) and the effects of two weeks of abstinence from smoking on levels of F2-isoprostanes in the circulation were also determined in the smokers. Plasma levels of free and esterified F2-isoprostanes were significantly higher in the smokers (242 +/- 147 and 574 +/- 217 pmol per liter, respectively) than in the nonsmokers (103 +/- 19 and 345 +/- 65 pmol per liter; P = 0.02 for free F2-isoprostanes and P = 0.03 for esterified F2-isoprostanes). Smoking had no short-term effects on the circulating levels of F2-isoprostanes. However, the levels of free and esterified F2-isoprostanes fell significantly after two weeks of abstinence from smoking (250 +/- 156 and 624 +/- 214 pmol per liter, respectively, before the cessation of smoking, as compared with 156 +/- 67 and 469 +/- 108 pmol per liter after two weeks' cessation; P = 0.03 for free F2-isoprostanes and P = 0.02 for esterified F2-isoprostanes). The increased levels of F2-isoprostanes in the circulation of persons who smoke support the hypothesis that smoking can cause the oxidative modification of important biologic molecules in vivo.
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            Reactive oxygen species, cell signaling, and cell injury

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              The isoprostanes

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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2002
                2002
                15 January 2003
                : 20
                : 6
                : 537-542
                Affiliations
                Department of aNephrology, Kuang Tien General Hospital, Taichung and bGraduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan
                Article
                66962 Blood Purif 2002;20:537–542
                10.1159/000066962
                12566669
                © 2002 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 2, Tables: 1, References: 42, Pages: 6
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/66962
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