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. 1991 Jul 1;277(Pt 1):133–138. doi: 10.1042/bj2770133

Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Protective effects of ascorbic acid.

B Frei 1, T M Forte 1, B N Ames 1, C E Cross 1
PMCID: PMC1151201  PMID: 1854329

Abstract

Cigarette smoke (CS) is known to contain a large number of oxidants. In order to assess the oxidative effects of CS on biological fluids, we exposed human blood plasma to filtered (gas phase) and unfiltered (whole) CS, and determined the rate of utilization of endogenous antioxidants in relation to the appearance of lipid hydroperoxides. Lipid peroxidation was measured with a specific and sensitive assay that can detect lipid hydroperoxides at plasma levels as low as 10 nM. We found that exposure of plasma to the gas phase of CS, but not to whole CS, induces lipid peroxidation once endogenous ascorbic acid has been oxidized completely. In addition, CS exposure caused oxidation of plasma protein thiols and albumin-bound bilirubin, whereas uric acid and alpha-tocopherol were not consumed at significant rates. In plasma exposed to the gas phase of CS, low-density lipoprotein exhibited slightly increased electrophoretic mobility, but there was no apparent degradation of apolipoprotein B. Our results support the concept of an increased vitamin C utilization in smokers, and suggest that lipid peroxidation induced by oxidants present in the gas phase of CS leads to potentially atherogenic changes in lipoproteins.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cantin A., Crystal R. G. Oxidants, antioxidants and the pathogenesis of emphysema. Eur J Respir Dis Suppl. 1985;139:7–17. [PubMed] [Google Scholar]
  2. Cerutti P. A. Prooxidant states and tumor promotion. Science. 1985 Jan 25;227(4685):375–381. doi: 10.1126/science.2981433. [DOI] [PubMed] [Google Scholar]
  3. Chow C. K., Thacker R. R., Changchit C., Bridges R. B., Rehm S. R., Humble J., Turbek J. Lower levels of vitamin C and carotenes in plasma of cigarette smokers. J Am Coll Nutr. 1986;5(3):305–312. doi: 10.1080/07315724.1986.10720134. [DOI] [PubMed] [Google Scholar]
  4. Church D. F., Pryor W. A. Free-radical chemistry of cigarette smoke and its toxicological implications. Environ Health Perspect. 1985 Dec;64:111–126. doi: 10.1289/ehp.8564111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cross C. E., Forte T., Stocker R., Louie S., Yamamoto Y., Ames B. N., Frei B. Oxidative stress and abnormal cholesterol metabolism in patients with adult respiratory distress syndrome. J Lab Clin Med. 1990 Apr;115(4):396–404. [PubMed] [Google Scholar]
  6. Cross C. E., Halliwell B., Borish E. T., Pryor W. A., Ames B. N., Saul R. L., McCord J. M., Harman D. Oxygen radicals and human disease. Ann Intern Med. 1987 Oct;107(4):526–545. doi: 10.7326/0003-4819-107-4-526. [DOI] [PubMed] [Google Scholar]
  7. Dousset N., Negre-Salvayre A., Lopez M., Salvayre R., Douste-Blazy L. Ultraviolet-treated lipoproteins as a model system for the study of the biological effects of lipid peroxides on cultured cell. I. Chemical modifications of ultraviolet-treated low-density lipoproteins. Biochim Biophys Acta. 1990 Aug 6;1045(3):219–223. doi: 10.1016/0005-2760(90)90123-f. [DOI] [PubMed] [Google Scholar]
  8. ELLMAN G. L. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959 May;82(1):70–77. doi: 10.1016/0003-9861(59)90090-6. [DOI] [PubMed] [Google Scholar]
  9. Esterbauer H., Striegl G., Puhl H., Oberreither S., Rotheneder M., el-Saadani M., Jürgens G. The role of vitamin E and carotenoids in preventing oxidation of low density lipoproteins. Ann N Y Acad Sci. 1989;570:254–267. doi: 10.1111/j.1749-6632.1989.tb14925.x. [DOI] [PubMed] [Google Scholar]
  10. Esterbauer H., Striegl G., Puhl H., Rotheneder M. Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Radic Res Commun. 1989;6(1):67–75. doi: 10.3109/10715768909073429. [DOI] [PubMed] [Google Scholar]
  11. Frei B., England L., Ames B. N. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6377–6381. doi: 10.1073/pnas.86.16.6377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Frei B., Stocker R., Ames B. N. Antioxidant defenses and lipid peroxidation in human blood plasma. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9748–9752. doi: 10.1073/pnas.85.24.9748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Frei B., Yamamoto Y., Niclas D., Ames B. N. Evaluation of an isoluminol chemiluminescence assay for the detection of hydroperoxides in human blood plasma. Anal Biochem. 1988 Nov 15;175(1):120–130. doi: 10.1016/0003-2697(88)90369-7. [DOI] [PubMed] [Google Scholar]
  14. Galdston M., Melnick E. L., Goldring R. M., Levytska V., Curasi C. A., Davis A. L. Interactions of neutrophil elastase, serum trypsin inhibitory activity, and smoking history as risk factors for chronic obstructive pulmonary disease in patients with MM, MZ, and ZZ phenotypes for alpha-antitrypsin. Am Rev Respir Dis. 1977 Nov;116(5):837–846. doi: 10.1164/arrd.1977.116.5.837. [DOI] [PubMed] [Google Scholar]
  15. Haapanen A., Koskenvuo M., Kaprio J., Kesäniemi Y. A., Heikkilä K. Carotid arteriosclerosis in identical twins discordant for cigarette smoking. Circulation. 1989 Jul;80(1):10–16. doi: 10.1161/01.cir.80.1.10. [DOI] [PubMed] [Google Scholar]
  16. Harats D., Ben-Naim M., Dabach Y., Hollander G., Havivi E., Stein O., Stein Y. Effect of vitamin C and E supplementation on susceptibility of plasma lipoproteins to peroxidation induced by acute smoking. Atherosclerosis. 1990 Nov;85(1):47–54. doi: 10.1016/0021-9150(90)90181-h. [DOI] [PubMed] [Google Scholar]
  17. Harats D., Ben-Naim M., Dabach Y., Hollander G., Stein O., Stein Y. Cigarette smoking renders LDL susceptible to peroxidative modification and enhanced metabolism by macrophages. Atherosclerosis. 1989 Oct;79(2-3):245–252. doi: 10.1016/0021-9150(89)90130-5. [DOI] [PubMed] [Google Scholar]
  18. Heinecke J. W., Rosen H., Chait A. Iron and copper promote modification of low density lipoprotein by human arterial smooth muscle cells in culture. J Clin Invest. 1984 Nov;74(5):1890–1894. doi: 10.1172/JCI111609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Henriksen T., Mahoney E. M., Steinberg D. Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors for acetylated low density lipoproteins. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6499–6503. doi: 10.1073/pnas.78.10.6499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hoidal J. R., Niewoehner D. E. Lung phagocyte recruitment and metabolic alterations induced by cigarette smoke in humans and in hamsters. Am Rev Respir Dis. 1982 Sep;126(3):548–552. doi: 10.1164/arrd.1982.126.3.548. [DOI] [PubMed] [Google Scholar]
  21. Hunninghake G. W., Crystal R. G. Cigarette smoking and lung destruction. Accumulation of neutrophils in the lungs of cigarette smokers. Am Rev Respir Dis. 1983 Nov;128(5):833–838. doi: 10.1164/arrd.1983.128.5.833. [DOI] [PubMed] [Google Scholar]
  22. Janero D. R. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med. 1990;9(6):515–540. doi: 10.1016/0891-5849(90)90131-2. [DOI] [PubMed] [Google Scholar]
  23. Jialal I., Vega G. L., Grundy S. M. Physiologic levels of ascorbate inhibit the oxidative modification of low density lipoprotein. Atherosclerosis. 1990 Jun;82(3):185–191. doi: 10.1016/0021-9150(90)90039-l. [DOI] [PubMed] [Google Scholar]
  24. Kostis J. B., Turkevich D., Sharp J. Association between leukocyte count and the presence and extent of coronary atherosclerosis as determined by coronary arteriography. Am J Cardiol. 1984 Apr 1;53(8):997–999. doi: 10.1016/0002-9149(84)90624-6. [DOI] [PubMed] [Google Scholar]
  25. Krauss R. M., Burke D. J. Identification of multiple subclasses of plasma low density lipoproteins in normal humans. J Lipid Res. 1982 Jan;23(1):97–104. [PubMed] [Google Scholar]
  26. Lentz P. E., Di Luzio N. R. Peroxidation of lipids in alveolar macrophages. Production by aqueous extracts of cigarette smoke. Arch Environ Health. 1974 May;28(5):279–282. doi: 10.1080/00039896.1974.10666487. [DOI] [PubMed] [Google Scholar]
  27. Lenz M. L., Hughes H., Mitchell J. R., Via D. P., Guyton J. R., Taylor A. A., Gotto A. M., Jr, Smith C. V. Lipid hydroperoxy and hydroxy derivatives in copper-catalyzed oxidation of low density lipoprotein. J Lipid Res. 1990 Jun;31(6):1043–1050. [PubMed] [Google Scholar]
  28. Ludwig P. W., Hoidal J. R. Alterations in leukocyte oxidative metabolism in cigarette smokers. Am Rev Respir Dis. 1982 Dec;126(6):977–980. doi: 10.1164/arrd.1982.126.6.977. [DOI] [PubMed] [Google Scholar]
  29. MacNee W., Selby C. Neutrophil kinetics in the lungs. Clin Sci (Lond) 1990 Aug;79(2):97–107. doi: 10.1042/cs0790097. [DOI] [PubMed] [Google Scholar]
  30. Mjøs O. D. Lipid effects of smoking. Am Heart J. 1988 Jan;115(1 Pt 2):272–275. doi: 10.1016/0002-8703(88)90649-7. [DOI] [PubMed] [Google Scholar]
  31. Murata A., Shiraishi I., Fukuzaki K., Kitahara T., Harada Y. Lower levels of vitamin C in plasma and urine of Japanese male smokers. Int J Vitam Nutr Res. 1989;59(2):184–189. [PubMed] [Google Scholar]
  32. Musliner T. A., Giotas C., Krauss R. M. Presence of multiple subpopulations of lipoproteins of intermediate density in normal subjects. Arteriosclerosis. 1986 Jan-Feb;6(1):79–87. doi: 10.1161/01.atv.6.1.79. [DOI] [PubMed] [Google Scholar]
  33. Nesje L. A., Mjøs O. D. Plasma HDL cholesterol and the subclasses HDL2 and HDL3 in smokers and non-smokers. Artery. 1985;13(1):7–18. [PubMed] [Google Scholar]
  34. Parthasarathy S., Barnett J., Fong L. G. High-density lipoprotein inhibits the oxidative modification of low-density lipoprotein. Biochim Biophys Acta. 1990 May 22;1044(2):275–283. doi: 10.1016/0005-2760(90)90314-n. [DOI] [PubMed] [Google Scholar]
  35. Parthasarathy S., Steinbrecher U. P., Barnett J., Witztum J. L., Steinberg D. Essential role of phospholipase A2 activity in endothelial cell-induced modification of low density lipoprotein. Proc Natl Acad Sci U S A. 1985 May;82(9):3000–3004. doi: 10.1073/pnas.82.9.3000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Pryor W. A., Dooley M. M., Church D. F. Mechanisms of cigarette smoke toxicity: the inactivation of human alpha-1-proteinase inhibitor by nitric oxide/isoprene mixtures in air. Chem Biol Interact. 1985 Jul;54(2):171–183. doi: 10.1016/s0009-2797(85)80161-7. [DOI] [PubMed] [Google Scholar]
  37. Pryor W. A., Prier D. G., Church D. F. Electron-spin resonance study of mainstream and sidestream cigarette smoke: nature of the free radicals in gas-phase smoke and in cigarette tar. Environ Health Perspect. 1983 Jan;47:345–355. doi: 10.1289/ehp.8347345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Schwalb G., Anderson R. Increased frequency of oxidant-mediated DNA strand breaks in mononuclear leucocytes exposed to activated neutrophils from cigarette smokers. Mutat Res. 1989 Mar;225(3):95–99. doi: 10.1016/0165-7992(89)90124-3. [DOI] [PubMed] [Google Scholar]
  39. Steinberg D., Parthasarathy S., Carew T. E., Khoo J. C., Witztum J. L. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989 Apr 6;320(14):915–924. doi: 10.1056/NEJM198904063201407. [DOI] [PubMed] [Google Scholar]
  40. Steinbrecher U. P., Pritchard P. H. Hydrolysis of phosphatidylcholine during LDL oxidation is mediated by platelet-activating factor acetylhydrolase. J Lipid Res. 1989 Mar;30(3):305–315. [PubMed] [Google Scholar]
  41. Yamamoto Y., Frei B., Ames B. N. Assay of lipid hydroperoxides using high-performance liquid chromatography with isoluminal chemiluminescence detection. Methods Enzymol. 1990;186:371–380. doi: 10.1016/0076-6879(90)86130-n. [DOI] [PubMed] [Google Scholar]
  42. Yokode M., Kita T., Arai H., Kawai C., Narumiya S., Fujiwara M. Cholesteryl ester accumulation in macrophages incubated with low density lipoprotein pretreated with cigarette smoke extract. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2344–2348. doi: 10.1073/pnas.85.7.2344. [DOI] [PMC free article] [PubMed] [Google Scholar]

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