Cardiovascular disease is the major complication and cause of mortality in the dialysis population, accounting for about 40% of deaths. Oxidative stress has been strongly implicated in the pathogenesis of these events. As patients in end-stage renal disease (ESRD) are in a state of elevated free radical activity, the aim of the present study was to investigate the negative impact of smoking in 45 male hemodialysis (HD) patients. These patients, who were 40–85 years of age (mean age 60.9 ± 13.3 years), had been on hemodialysis for at least 12 months before participating in this study. Fasting blood sampling for serum lipid, albumin, urate, lipid peroxides total blood glutathione (tGSH), non-GSH free sulfhydryl compounds (non-GSH fSH), plasma glutathione peroxidase (pGSHPx), erythrocytes glutathione peroxidase (rGSHPx), plasma glutathione S-transferase (pGST) and erythrocytes glutathione S-transferase (rGST) were determined. Our study showed that the plasma malonyldialdehyde (MDA) concentration was significantly higher in HD patients who smoked than in those who were non- smokers (1.99 ± 0.53 vs. 1.55 ± 0.46 nmol/ml, p = 0.008). No association was found between levels of MDA in smokers and BMI, serum cholesterol and triglycerides and smoking index. We also found that the circulating plasma levels of tGSH and non-GSH fSH was lower in the HD patients who smoked (tGSH 164.9 ± 41.5 vs. 203.4 ± 45.3 µg/ml; fSH 271.1 ± 55.8 vs. 308.8 ± 46.7 µg/ml; p < 0.05 and p < 0.001, respectively). There were no significant differences in the plasma levels of uric acid, pGSHPx, rGSHPx, pGST, rGST, albumin, and age between the 2 groups. Partial correlation analysis of the plasma levels of the measured antioxidants and the smoking index revealed a negative correlation between the plasma levels of tGSH and smoking index (r = –0.62, p < 0.003). Similarly, the plasma levels of tGSH was found negatively correlated with the levels of plasma MDA (r = –0.32, p < 0.05) of the HD patients. In conclusion, our data suggest that cigarette smoking has a negative impact on plasma-circulating products of lipid peroxidation in HD patients. The lower blood levels of the tGSH and non-GSH fSH in HD patients who smoked suggests that these patients may be more susceptible to oxidative damage caused by smoking.

Keywords:
Glutathione, Smoking, Hemodialysis, Lipid peroxides
1.
USRDS 1994 Annual Report: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md., 1994.
2.
Foley RN, Parfrey PS, Sarnak MJ: Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998;32(suppl 3):S112–S119.
3.
Parfrey PS, Foley RN, Harnett JD, Kent GM, Murray D, Barre PE: Outcome and risk factors of ischemic heart disease in chronic uremia. Kidney Int 1996;49:1428–1434.
4.
Kaul N, Siveski-Iliskovich N, Hill M, Slezak J, Singal PK: Free radicals and the heart. J Pharmacol Toxicol Methods 1993;30:55–67.
5.
Himmelfarb J, Lazarus M, Hakim R: Reactive oxygen species production by monocytes and polymorphonuclear leukocytes during dialysis. Am J Kidney Dis 1991;17:271–276.
6.
Luciak M, Trznadel K: Free oxygen species metabolism during hemodialyis with different membranes. Nephrol Dial Transplant Suppl 1991;3:66–70.
7.
Mimimic-Oka J, Simic T, Djukanovic L, Reljic Z, Davicevic A: Alteration in plasma antioxidant capacity in various degrees of chronic renal failure. Clin Nephrol 199;51:233–241.
8.
Loughrey CM, Young IS, Lightbody JH, McMaster D, McNamee PT, Trimble ER: Oxidative stress in hemodialysis. Q J Med 1994;87:679–683.
9.
Peuchant E, Carbonneau MA, Dubourg L, Thomas MJ, Perromat A, Vallot C, Clerc M: Lipoperoxidation in plasma and red blood cells of patients undergoing hemodialysis: Vitamins A, E and iron status. Free Radic Biol Med 1994;16:339–346.
10.
Orth SR, Viedt C, Ritz E: Adverse effects of smoking in the renal patient. Tohoku J Exp Med 2001;194:1–15.
11.
Church DF, Pryor WA: Free radical chemistry of cigarette smoke and its toxicological implications. Environ Health Perspect 1985;64:111–126.
12.
Morrow JD, Frei B, Longmire AW, Gaziano JM, Lynch SM, Shyr Y, Strauss WE, Oates JA, Roberts LJ: Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers: Smoking as a cause of oxidative damage. N Engl J Med 1995;332:1198–1203.
13.
Scheffler E, Wiest E, Woehrle J, Otto I, Schylz I, Huber I, Ziegler R, Dresel HA: Smoking influences the atherogenic potential of low-density lipoprotein. Clin Invest 1992;70:263–268.
14.
Harats D, Ben-Naim M, Dabach Y, Hollander G, Stein O, Stein Y: Cigarette smoke renders LDL susceptible to peroxidative modification and enhanced metabolism by macrophages. Atherosclerosis 1989;79:245–252.
15.
Stryker WS, Kaplan LA, Stein EA, Stampfer MJ, Sober A, Willen WC: The relation of diet, cigarette smoking and alcohol consumption to plasma beta-carotene and alpha tocopherol levels. Am J Epidemiol 1988;127:282–296.
16.
Liu CS, Chen HW, Li CK, Chen SC, Wei YH: Alterations of small-molecular weight antioxidants in the blood of smokers. Chem Biol Interact 1998;116:143–154.
17.
Fahn HJ, Wang LS, Kao SH, Chang SC, Huang MH, Wei YH: Am J Respir Cell Mol Biol 1998;19:901–909.
18.
Asami S, Hirano T, Yamaguchi R, Tomioka Y, Itoh H, Kasai H: Increase of a type of oxidative DNA damage, 8-hydroxyguanine and its repair activity in human leukocytes by cigarette smoking. Cancer Res 1996;94:119–125.
19.
Travis J: Oxidants and antioxidants in the lung. Am Rev Respir Dis 1987;135:773–774.
20.
Pan WH, Lee MM, Yu SL, Huang PC: Food predictive of nutrient intake in Chinese diet in Taiwan. II. Vitamin A, vitamin B1, vitamin B2, vitamin C and calcium. Int J Epidemiol 1992;21;929–934.
21.
Anderson ME, Meister A: Dynamic state of glutathione in blood plasma. J Biol Chem 1980;255:9530–9533.
22.
Ellman GL : Tissue sulfhydryl groups. Arch Biochem Biophys 1969;82:70–77.
23.
Flohe I, Gunzer WA: Assays of glutathione peroxidase. Methods Enzymol 1994;105:114–121.
24.
Habig WH, Pabst MJ, Jaloby WB: Gluthathione S-transferase: The first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130–7139.
25.
Wong SHY, Knight JA, Hopfer SM, Zaharia O, Leach CN, Sunderman FW: Lipoperoxides in plasma as measured by liquid-chromatographic separation of malondialdehyde-thiobarbituric acid adduct. Clin Chem 1987;33:214–220.
26.
Lim PS, Wang NP, Lu TC, Wang TH, Hsu WM, Chan EC, Hung WR, Yang CC, Kuo IF, Wei YH: Evidence for alterations in circulating low-molecular-weight antioxidants and increased lipid peroxidation in smokers on hemodialysis. Nephron 2001;88:127–133.
27.
Eiserich JP, van der Vliet A, Handelman GJ, Halliwell B, Cross CE: Dietary antioxidants and cigarette smoke-induced biomolecular damage: A complex interaction. Am J Clin Nutr 1995;62:1490S–1500S.
28.
Amstad P, Moret R, Cerutti P: Glutathione peroxidase compensates for the hypersensitivity of Cu, Zn-superoxide dismutase overproducers to oxidant stress. J Biol Chem 1994;269:1606–1609.
29.
Toth KM, Berger EM, Beehler CJ, Repine JE: Erythrocytes from cigarette smokers contain more glutathione and catalase and protect endothelial cells from hydrogen peroxide better than do erythrocytes from non-smokers. Am Rev Respir Dis 1986;134:281–284.
30.
Michelet F, Gueguen R, Leroy P, Wellman M, Nicolas A, Siest G: Blood and plasma glutathione measured in healthy subjects by HPLC: Relation to sex, aging, biological variables, and life habits. Gen Clin Chem 1995;41:1509–1517.
31.
Liu CS, Wei YH: Age-associated alteration of blood thiol-group-related antioxidants in smokers. Environ Res 1999;80:18–24.
32.
Yang CS, Chou ST, Liu L, Tsai PJ, Kuo JS: Effect of ageing on human plasma glutathione concentrations as determined by high-performance liquid chromatography with fluorimetric detection. J Chromatogr [B] 1995;674:23–30.
33.
Lim PS, Wei YH, Yu YL, Kho B: Enhanced oxidative stress in hemodialysis patients receiving intravenous iron therapy. Nephrol Dial Transplant 1999;14:2680–2687.
34.
Galli F, Rovidati S, Benedetti S, Buoncristiani U, Covarelli C, Floridi A, Canestrari F: Overexpression of erythrocytes glutathione S-transferase in uremia and dialysis. Clin Chem 1999;45:1781–1788.
35.
Meister A: Metabolism and function of glutathione; in Dolphin D, Poulson R, Avramovic O (eds): Glutathione: Chemical, Biochemical and Medical Aspects. New York, Wiley, 1989, part A, pp 367–474.
36.
Roxborough HE, Mercer C, McMaster D, Maxwell AP, Young IS: Plasma glutathione peroxidase activity in hemodialysis patients. Nephron 1999;81:278–283.
37.
Yoshimura S, Suemizu H, Nomoto Y, Sakai H, Katsuoka Y, Kawamura N, Moriuchi T: Plasma glutathione peroxidase deficiency caused by renal dysfunction. Nephron 1996;73:207–211.
38.
Abou-Seif MA: Blood antioxidant status and urine sulfate and thiocyanate levels in smokers. J Biochem Toxicol 1996;11:133–138.
39.
Hulea SA, Olinescu R, Nita S, Crocnan D, Kummerow FA: Cigarette smoking causes biochemical changes in blood that suggestive of oxidative stress: A case-control study. J Environ Pathol Toxicol Oncol 1995;14:173–180.
40.
Andersen HR, Nielsen JB, Nielsen F, Grandjean P: Antioxidant enzyme activities in human erythrocytes. Clin Chem 1997;43:562–568.
41.
Codandabany U: Erythrocyte lipid peroxidation and antioxidants in cigarette smokers. Cell Biochem Funct 2000;18:99–102.
42.
Frei B, Forte TM, Ames BN, Cross CE: Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Biochem J 1991;277:133–138.
43.
Frei B: Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage: Am J Clin Nutr 1991;54 (suppl):1113S–1118S.
44.
Miller ER, Appel LJ, Jiang L, Risby TH: Association between cigarette smoking and lipid peroxidation in a controlled feeding study. Circulation 1997;96:1097–1101.
45.
Zoppini G, Targher G, Monauni T, Faccini G, Pasqualini E, Martinelli C, Zenari ML, Muggeo M: Increase in circulating products of lipid peroxidation in smokers with IDDM. Diabetes 1996;19:1233–1236.
46.
Leonard MB, Lawton K, Watson ID, Patrick A, Walker A, MacFarlane I: Cigarette smoking and free radical activity in young adults with insulin-dependent diabetes. Diabetic Med 1995;12:46–50.
47.
Janero DR: Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury: Free Radic Biol Med 1990;9:515–540.
© 2002 S. Karger AG, Basel
2002
Copyright / Drug Dosage / Disclaimer
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.
You do not currently have access to this content.