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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1998 Mar 15;101(6):1210–1218. doi: 10.1172/JCI1314

In vivo absorption, metabolism, and urinary excretion of alpha,beta-unsaturated aldehydes in experimental animals. Relevance to the development of cardiovascular diseases by the dietary ingestion of thermally stressed polyunsaturate-rich culinary oils.

M Grootveld 1, M D Atherton 1, A N Sheerin 1, J Hawkes 1, D R Blake 1, T E Richens 1, C J Silwood 1, E Lynch 1, A W Claxson 1
PMCID: PMC508674  PMID: 9502761

Abstract

Thermal stressing of polyunsaturated fatty acid (PUFA)- rich culinary oils according to routine frying or cooking practices generates high levels of cytotoxic aldehydic products (predominantly trans-2-alkenals, trans,trans-alka-2,4-dienals, cis,trans-alka-2, 4-dienals, and n-alkanals), species arising from the fragmentation of conjugated hydroperoxydiene precursors. In this investigation we demonstrate that typical trans-2-alkenal compounds known to be produced from the thermally induced autoxidation of PUFAs are readily absorbed from the gut into the systemic circulation in vivo, metabolized (primarily via the addition of glutathione across their electrophilic carbon-carbon double bonds), and excreted in the urine as C-3 mercapturate conjugates in rats. Since such aldehydic products are damaging to human health, the results obtained from our investigations indicate that the dietary ingestion of thermally, autoxidatively stressed PUFA-rich culinary oils promotes the induction, development, and progression of cardiovascular diseases.

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Selected References

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  1. Addis P. B. Occurrence of lipid oxidation products in foods. Food Chem Toxicol. 1986 Oct-Nov;24(10-11):1021–1030. doi: 10.1016/0278-6915(86)90283-8. [DOI] [PubMed] [Google Scholar]
  2. Barrowcliffe T. W., Gray E., Kerry P. J., Gutteridge J. M. Triglyceride-rich lipoproteins are responsible for thrombin generation induced by lipid peroxides. Thromb Haemost. 1984 Aug 31;52(1):7–10. [PubMed] [Google Scholar]
  3. Bergan J. G., Draper H. H. Absorption and metabolism of 1-14C-methyl linoleate hydroperoxide. Lipids. 1970 Dec;5(12):976–982. doi: 10.1007/BF02533200. [DOI] [PubMed] [Google Scholar]
  4. Claxson A. W., Hawkes G. E., Richardson D. P., Naughton D. P., Haywood R. M., Chander C. L., Atherton M., Lynch E. J., Grootveld M. C. Generation of lipid peroxidation products in culinary oils and fats during episodes of thermal stressing: a high field 1H NMR study. FEBS Lett. 1994 Nov 21;355(1):81–90. doi: 10.1016/0014-5793(94)01147-8. [DOI] [PubMed] [Google Scholar]
  5. Cortesi R., Privett O. S. Toxicity of fatty ozonides and peroxides. Lipids. 1972 Nov;7(11):715–721. doi: 10.1007/BF02533120. [DOI] [PubMed] [Google Scholar]
  6. Draminski W., Eder E., Henschler D. A new pathway of acrolein metabolism in rats. Arch Toxicol. 1983 Mar;52(3):243–247. doi: 10.1007/BF00333903. [DOI] [PubMed] [Google Scholar]
  7. Draper H. H., Hadley M., Lissemore L., Laing N. M., Cole P. D. Identification of N-epsilon-(2-propenal)lysine as a major urinary metabolite of malondialdehyde. Lipids. 1988 Jun;23(6):626–628. doi: 10.1007/BF02535610. [DOI] [PubMed] [Google Scholar]
  8. Gurtoo H. L., Marinello A. J., Struck R. F., Paul B., Dahms R. P. Studies on the mechanism of denaturation of cytochrome P-450 by cyclophosphamide and its metabolites. J Biol Chem. 1981 Nov 25;256(22):11691–11701. [PubMed] [Google Scholar]
  9. Gutteridge J. M., Lamport P., Dormandy T. L. The antibacterial effect of water-soluble compounds from autoxidising linolenic acid. J Med Microbiol. 1976 Feb;9(1):105–110. doi: 10.1099/00222615-9-1-105. [DOI] [PubMed] [Google Scholar]
  10. Haberland M. E., Fogelman A. M., Edwards P. A. Specificity of receptor-mediated recognition of malondialdehyde-modified low density lipoproteins. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1712–1716. doi: 10.1073/pnas.79.6.1712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hadley M., Draper H. H. Identification of N-(2-propenal) serine as a urinary metabolite of malondialdehyde. FASEB J. 1988 Feb;2(2):138–140. doi: 10.1096/fasebj.2.2.3125082. [DOI] [PubMed] [Google Scholar]
  12. Hadley M., Draper H. H. Identification of N-(2-propenal)ethanolamine as a urinary metabolite of malondialdehyde. Free Radic Biol Med. 1989;6(1):49–52. doi: 10.1016/0891-5849(89)90159-7. [DOI] [PubMed] [Google Scholar]
  13. Hadley M., Draper H. H. Isolation of a guanine-malondialdehyde adduct from rat and human urine. Lipids. 1990 Feb;25(2):82–85. doi: 10.1007/BF02562209. [DOI] [PubMed] [Google Scholar]
  14. Haywood R. M., Claxson A. W., Hawkes G. E., Richardson D. P., Naughton D. P., Coumbarides G., Hawkes J., Lynch E. J., Grootveld M. C. Detection of aldehydes and their conjugated hydroperoxydiene precursors in thermally-stressed culinary oils and fats: investigations using high resolution proton NMR spectroscopy. Free Radic Res. 1995 May;22(5):441–482. doi: 10.3109/10715769509147552. [DOI] [PubMed] [Google Scholar]
  15. Hess J. L., Pallansch M. A., Harich K., Bunce G. E. Quantitative determination of alpha-tocopherol on thin layers of silica gel. Anal Biochem. 1977 Dec;83(2):401–407. doi: 10.1016/0003-2697(77)90049-5. [DOI] [PubMed] [Google Scholar]
  16. Hoff H. F., O'Neil J., Chisolm G. M., 3rd, Cole T. B., Quehenberger O., Esterbauer H., Jürgens G. Modification of low density lipoprotein with 4-hydroxynonenal induces uptake by macrophages. Arteriosclerosis. 1989 Jul-Aug;9(4):538–549. doi: 10.1161/01.atv.9.4.538. [DOI] [PubMed] [Google Scholar]
  17. Jürgens G., Hoff H. F., Chisolm G. M., 3rd, Esterbauer H. Modification of human serum low density lipoprotein by oxidation--characterization and pathophysiological implications. Chem Phys Lipids. 1987 Nov-Dec;45(2-4):315–336. doi: 10.1016/0009-3084(87)90070-3. [DOI] [PubMed] [Google Scholar]
  18. Kanazawa K., Kanazawa E., Natake M. Uptake of secondary autoxidation products of linoleic acid by the rat. Lipids. 1985 Jul;20(7):412–419. doi: 10.1007/BF02534231. [DOI] [PubMed] [Google Scholar]
  19. Kaunitz H. Medium chain triglycerides (MCT) in aging and arteriosclerosis. J Environ Pathol Toxicol Oncol. 1986 Mar-Apr;6(3-4):115–121. [PubMed] [Google Scholar]
  20. Kaye C. M. Biosynthesis of mercapturic acids from allyl alcohol, allyl esters and acrolein. Biochem J. 1973 Aug;134(4):1093–1101. doi: 10.1042/bj1341093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kingsbury K. J., Brett C., Stovold R., Chapman A., Anderson J., Morgan D. M. Abnormal fatty acid composition and human atherosclerosis. Postgrad Med J. 1974 Jul;50(585):425–440. doi: 10.1136/pgmj.50.585.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kristal B. S., Yu B. P. An emerging hypothesis: synergistic induction of aging by free radicals and Maillard reactions. J Gerontol. 1992 Jul;47(4):B107–B114. doi: 10.1093/geronj/47.4.b107. [DOI] [PubMed] [Google Scholar]
  23. Kritchevsky D. Dietary fat and experimental atherosclerosis. Int J Tissue React. 1991;13(2):59–65. [PubMed] [Google Scholar]
  24. Kritchevsky D., Tepper S. A. Cholesterol vehicle in experimental atherosclerosis. 9. Comparison of heated corn oil and heated olive oil. J Atheroscler Res. 1967 Sep-Oct;7(5):647–651. doi: 10.1016/s0368-1319(67)80041-3. [DOI] [PubMed] [Google Scholar]
  25. Martin W. The combined role of atheroma, cholesterol, platelets, the endothelium and fibrin in heart attacks and strokes. Med Hypotheses. 1984 Nov;15(3):305–322. doi: 10.1016/0306-9877(84)90021-5. [DOI] [PubMed] [Google Scholar]
  26. OLCOTT H. S., DOLEV A. TOXICITY OF FATTY ACID ESTER HYDROPEROXIDES. Proc Soc Exp Biol Med. 1963 Dec;114:820–822. doi: 10.3181/00379727-114-28809. [DOI] [PubMed] [Google Scholar]
  27. Oliver M. F. Cigarette smoking, polyunsaturated fats, linoleic acid, and coronary heart disease. Lancet. 1989 Jun 3;1(8649):1241–1243. doi: 10.1016/s0140-6736(89)92338-6. [DOI] [PubMed] [Google Scholar]
  28. Parthasarathy S., Khoo J. C., Miller E., Barnett J., Witztum J. L., Steinberg D. Low density lipoprotein rich in oleic acid is protected against oxidative modification: implications for dietary prevention of atherosclerosis. Proc Natl Acad Sci U S A. 1990 May;87(10):3894–3898. doi: 10.1073/pnas.87.10.3894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Selley M. L., Bourne D. J., Bartlett M. R., Tymms K. E., Brook A. S., Duffield A. M., Ardlie N. G. Occurrence of (E)-4-hydroxy-2-nonenal in plasma and synovial fluid of patients with rheumatoid arthritis and osteoarthritis. Ann Rheum Dis. 1992 Apr;51(4):481–484. doi: 10.1136/ard.51.4.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Staprãns I., Rapp J. H., Pan X. M., Hardman D. A., Feingold K. R. Oxidized lipids in the diet accelerate the development of fatty streaks in cholesterol-fed rabbits. Arterioscler Thromb Vasc Biol. 1996 Apr;16(4):533–538. doi: 10.1161/01.atv.16.4.533. [DOI] [PubMed] [Google Scholar]
  31. Turner S. R., Campbell J. A., Lynn W. S. Polymorphonulcear leukocyte chemotaxis toward oxidized lipid components of cell membranes. J Exp Med. 1975 Jun 1;141(6):1437–1441. doi: 10.1084/jem.141.6.1437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Van Hinsbergh V. W. LDL cytotoxicity. The state of the art. Atherosclerosis. 1984 Nov;53(2):113–118. doi: 10.1016/0021-9150(84)90188-6. [DOI] [PubMed] [Google Scholar]
  33. Whitman S. C., Fish J. R., Rand M. L., Rogers K. A. n-3 fatty acid incorporation into LDL particles renders them more susceptible to oxidation in vitro but not necessarily more atherogenic in vivo. Arterioscler Thromb. 1994 Jul;14(7):1170–1176. doi: 10.1161/01.atv.14.7.1170. [DOI] [PubMed] [Google Scholar]
  34. Winter C. K., Segall H. J., Jones A. D. Distribution of trans-4-hydroxy-2-hexenal and tandem mass spectrometric detection of its urinary mercapturic acid in the rat. Drug Metab Dispos. 1987 Sep-Oct;15(5):608–612. [PubMed] [Google Scholar]
  35. Witz G. Biological interactions of alpha,beta-unsaturated aldehydes. Free Radic Biol Med. 1989;7(3):333–349. doi: 10.1016/0891-5849(89)90137-8. [DOI] [PubMed] [Google Scholar]

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