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Intestinal Absorption and Metabolism of Peroxidized Lipids

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Intestinal Lipid Metabolism

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Abstract

The intestine is unique among all fully differentiated organs in that it sits at the interface between the organism and its lumenal environment. In this regard, the intestine is a primary site of nutrient absorption and a critical defense barrier against dietary-derived mutagens, carcinogens, and oxidants. An important class of oxidants present in the human diet is lipid hydroperoxides, which are toxic products of oxidized polyunsaturated fats. Accumulation of peroxidized lipids in the gut lumen can contribute to impairment of mucosal metabolic pathways, enterocyte dysfunction independent of cell injury, and development of gut pathologies, such as cancer. Despite this recognition, and the implication of dietary peroxidized lipids in gut pathologies, we know little of the underlying mechanisms of the genesis of the disease processes or of the pathways of intestinal metabolism and lumenal disposition of dietary lipid hydroperoxides in vivo. This chapter summarizes our current understanding of the determinants of the intestinal absorption and metabolism of peroxidized lipids. In particular, we review the evidence supporting the pivotal role that GSH and NADPH play in the overall mucosal metabolism of toxic lipid hydroperoxides, and how reductant availability can be compromised under certain pathophysiological conditions, such as chronic hypoxia. The discussion is pertinent to understanding dietary lipid peroxides and GSH redox balance in intestinal physiology and pathophysiology and the significance of lumenal GSH in preserving the metabolic integrity of the intestinal epithelium.

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References

  • Ames, B. N., 1983, Dietary carcinogens and anticarcinogens: Oxygen radicals and degenerative diseases, Science 221:1256–1264.

    Article  PubMed  CAS  Google Scholar 

  • Andreoli, S. P., Mallett, C. P., and Bergstein, J. M., 1986, Role of glutathione in protecting endothelial cells against hydrogen peroxide oxidant injury, J. Lab. Clin. Med. 108:190–198.

    PubMed  CAS  Google Scholar 

  • Andrews, J. S., Griffith, W. H., Mead, J. F., and Stein, R. A., 1960, Toxicity of air-oxidized soybean oil, J. Nutr.70:199–210.

    PubMed  CAS  Google Scholar 

  • Aw, T. Y., 1994, Biliary glutathione promotes the mucosal metabolism of lumenal peroxidized lipids by rat small intestine in vivo, J. Clin. Invest 94(September): 1218–1225.

    Article  PubMed  CAS  Google Scholar 

  • Aw, T. Y., 1997, Lumenal peroxides in intestinal thiol-disulfide balance and cell turnover, Comp. Biochem. Phys-ioi 118B(3):479–485.

    Article  CAS  Google Scholar 

  • Aw, T. Y, and Rhoads, C. A., 1994, Glucose regulation of hydroperoxide metabolism in rat intestinal cells, J. Clin.Invest. 94:2426–2434.

    Article  PubMed  CAS  Google Scholar 

  • Aw, T. Y, and Williams, M. W., 1992, Intestinal absorption and lymphatic transport of peroxidized lipids in rats:effect of exogenous GSH, Am. J. Physiol. 263:G665–G672.

    PubMed  CAS  Google Scholar 

  • Aw, T. Y., Andersson, B. S., and Jones, D. P., 1987, Suppression of mitochondrial respiratory function after short-term anoxia, Am. J. Physiol. 252:C362–C368.

    PubMed  CAS  Google Scholar 

  • Aw, T. Y., Shan, X., Sillau, A. H., and Jones, D. P., 1991, Effect of chronic hypoxia on acetaminophen metabolism in the rat, Biochem. Pharmacol 42(5): 1029–1038.

    Article  PubMed  CAS  Google Scholar 

  • Aw, T. Y., Williams, M. W., and Gray, L., 1992, Absorption and lymphatic transport of peroxidized lipids by rat small intestine in vivo: Role of mucosal GSH, Am. J. Physiol. 262:G99–G106.

    PubMed  CAS  Google Scholar 

  • Aw, T. Y., Smith, D. S., and Williams, A. D., 1993, Decreases in mucosal glutathione (GSH) promote portal transport of omega-3 fatty acid hydroperoxides in vivo, FASEB J. 7(3):A385.

    Google Scholar 

  • Bai, C., and Jones, D. P., 1996, GSH transport and GSH-dependent detoxication in small intestine of rats exposed in vivo to hypoxia, Am. J. Physiol. 271:G701–G706.

    PubMed  CAS  Google Scholar 

  • Bergan, F. G., and Draper, H. H., 1970, Absorption and metabolism of l-14C-methyl linoleate hydroperoxide, Lipids 5:976–982.

    Article  PubMed  CAS  Google Scholar 

  • Bousignone, A., and Flora, A. D., 1972, Regulatory properties of glucose 6-phosphate dehydrogenase, Current Topics in Cell Regulation 6:21–62.

    Google Scholar 

  • Boyer, S. J., and Blume, F. D., 1984, Weight loss and changes in body composition at high altitude, J. Appl. Physiol. 57: 1580–1585.

    PubMed  CAS  Google Scholar 

  • Brigelius, R., 1985, Mixed disulfȹdes: Biological functions and increase in oxidative stress, in: Oxidative Stress. 1st ed. (H. Sies, ed.), Academic Press, Inc., London, pp. 243–272.

    Google Scholar 

  • Bull, A. W., Nigro, N. D., Golembieski, W. A., Crissman, J. D., and Marnett, L. J., 1984, In vivo stimulation of DNA synthesis and induction of ornithine decarboxylase in rat colon by fatty acid hydroperoxides autoxidation products of unsaturated fatty acids, Canc. Res. 44:4924–4928.

    CAS  Google Scholar 

  • Bunyan, J., Green, J., Murrell, E. A., Diplock, A. T., and Cawthorne, M. A., 1968, On the postulated peroxidation of unsaturated lipids in the tissues of vitamin E-deficient rats, Br. J. Nutr. 22:97–110.

    Article  PubMed  CAS  Google Scholar 

  • Burrows, B., Kettel, L. J., Niden, A. H., Rabinowitz, M., and Diener, C. R., 1972, Patterns of cardiovascular dysfunction in chronic obstructive pulmonary disease, N. Engl. J. Med. 286:912–918.

    Article  PubMed  CAS  Google Scholar 

  • Carroll, K. K., and Khor, H. T., 1975, Dietary fat in relation to tumorigenesis, Prog. Biochem. Pharmacol. 10:308–353.

    PubMed  CAS  Google Scholar 

  • Cerra, F. B., 1987, Hypermetabolism, organ failure, and metabolic support, Surgery 101:1–14.

    PubMed  CAS  Google Scholar 

  • Chu, F. F., Doroshow, J. H., and Esworthy, R. S., 1993, Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPX-GI, J. Biol. Chem. 268:2571–2576.

    PubMed  CAS  Google Scholar 

  • Correa, P., Strong, J. P., Johnson, W. D., Pizzolato, P., and Haenszel, W., 1982, Atherosclerosis and polyps of the colon: Quantification of precursors of coronary heart disease and colon cancer, J. Chronic Dis. 35:313–320.

    Article  PubMed  CAS  Google Scholar 

  • Eggleston, L. V., and Krebs, H. A., 1974, Regulation of the pentose phosphate cycle, Biochem. J. 138:425–435.

    PubMed  CAS  Google Scholar 

  • Fink, D. J., and Kritchevsky, D., 1981, Introduction to the workshop on fat and cancer, Cancer Res. 41:3684.

    PubMed  Google Scholar 

  • Fischer, S. M., Gleason, G. L., Mills, G. D., and Slaga, J. J., 1980, Indomethacin enhancement of TPA tumor promotion in mice, Canc. Lett. 10:343–350.

    Article  CAS  Google Scholar 

  • Girotti, A. W., 1985, Mechanisms of lipid peroxidation, J. Free Rad. Biol. Med. 1(2):87–95.

    Article  CAS  Google Scholar 

  • Glavind, J., 1970, Intestinal absorption and lymphatic transport of methyl linoleate hydroperoxide and hydroxy-octadecadienoate in the rat, Acta Chem. Scand. 24:3723–3728.

    Article  PubMed  CAS  Google Scholar 

  • Grisham, M. B., and Granger, D. N., 1988, Neutrophil-mediated mucosal injury: Role of reactive oxygen metabolites, Dig. Dis. Sci. 33:6S–15S.

    Article  PubMed  CAS  Google Scholar 

  • Hagen, T. M., and Jones, D. P., 1987, Transepithelial transport of glutathione in vascularly perfused small intestine of rat, Am. J. Physiol. 252:G607–G613.

    PubMed  CAS  Google Scholar 

  • Hagen, T. M., Brown, L. A., and Jones, D. P., 1986, Protection against paraquat induced injury by exogenous GSH in pulmonary alveolar type II cells, Biochem. Pharmacol. 35:4537–4542.

    Article  PubMed  CAS  Google Scholar 

  • Hagen, T. M., Aw, T. Y., and Jones, D. P., 1988, Glutathione uptake and protection against oxidative injury in isolated kidney cells, Kidney Int. 34:74–81.

    Article  PubMed  CAS  Google Scholar 

  • Hagen, T. M., Wierzbicka, G. T., Bowman, B. B., Aw, T. Y., and Jones, D. P., 1990, Fate of dietary glutathione: Disposition in the gastrointestinal tract, Am. J. Physiol. 259:G530–G535.

    PubMed  CAS  Google Scholar 

  • Hara, H., Miyashita, K., Ito, S., and Kasai, T., 1996, Oxidized ethyl linoleate induces mucosal hypertrophy of the large intestine and affects cecal fermentation of dietary fiber in rats, J. Nutr. 126:800–806.

    PubMed  CAS  Google Scholar 

  • Iwakiri, T., Rhoads, C. A., and Aw, T. Y., 1995, Determinants of hydroperoxide detoxification in diabetic rat intestine: Effect of insulin and fasting on the glutathione redox cycle, Metabolism 44(11): 1462–1468.

    Article  PubMed  CAS  Google Scholar 

  • Jaeschke, H., 1990a, Glutathione disulfide as index of oxidant stress in rat liver during hypoxia, Am. J. Physiol. 258:G499–G505.

    PubMed  CAS  Google Scholar 

  • Jaeschke, H., 1990b, Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo: The protective effect of allopurinol, J. Pharmacol. Exp. Ther. 255(3):935–941.

    PubMed  CAS  Google Scholar 

  • Jones, D. P., 1981, Hypoxia and drug metabolism, Biochem. Pharmacol. 30(10):1019–1023.

    Article  PubMed  CAS  Google Scholar 

  • Jones, D. P., and Mason, H. S., 1978, Gradients of 02 concentration in hepatocytes, J. Biol. Chem. 253(14):4874–4880.

    PubMed  CAS  Google Scholar 

  • Jones, D. P., Coates, R. J., Flagg, E. W., Eley, J. W., Block, G., Greenberg, R. S., Gunter, E. W., and Jackson, B., 1992, Glutathione in foods listed in the National Cancer Institute’s Health Habits and History Food Frequency Questionnaire, Nutr. Cancer 17:57–75.

    Article  PubMed  CAS  Google Scholar 

  • Jones, D. P., LeGrand, T. S., Aw, T. Y., Dillehay, D., Cohen, S. D., Khairallah, E. A., and Manautou, J. E., 1995, Effect of oxygen deficiency on acetaminophen (APAP) toxicity in mice, Toxicol. 15(1): 152.

    Google Scholar 

  • Kaneda, T., Sakai, H., and Ishii, S., 1955, Nutritive value or toxicity of highly unsaturated fatty acids, J. Biochem. 42:561–573.

    CAS  Google Scholar 

  • Kaplowitz, N., Aw, T. Y., and Ookhtens, M., 1985, The regulation of hepatic glutathione, Ann. Rev. Pharmacol. Toxicol. 25:715–744.

    Article  CAS  Google Scholar 

  • Kauffman, F. C., Evans, R. K., and Thurman, R. G., 1977, Alterations in nicotinamide and adenine nucleotide systems during mixed-function oxidation of p-nitroanisole in perfused livers from normal and phenobarbital-treated rats, Biochem. J. 166:583–592.

    PubMed  CAS  Google Scholar 

  • Kimura, T., Iida, K., and Takei, Y., 1984, Mechanisms of adverse effect of air-oxidized soybean oil-feeding in rats, J. Nutr. Sci. Vitaminology 30:125–133.

    Article  CAS  Google Scholar 

  • Kinlen, L. J., 1983, Fat and cancer (editorial), Br. Med. J. 286:1081–1082.

    Article  CAS  Google Scholar 

  • Kowalski, D. P., Feeley, R. M., and Jones, D. P., 1990, Use of exogenous glutathione for metabolism of peroxidized methyl linoleate in rat small intestine, J. Nutr. 120:1115–1121.

    PubMed  CAS  Google Scholar 

  • Lash, L. H., Hagen, T. M., and Jones, D. P., 1986, Exogenous glutathione protects intestinal epithelial cells from oxidative injury, Proc. Natl. Acad. Sci. USA 83:4641–4645.

    Article  PubMed  CAS  Google Scholar 

  • LeGrand, T. S., and Aw, T. Y, 1996, Chronic hypoxia and glutathione-dependent detoxication in rat small intestine, Am. J. Physiol. 270:G725–G729.

    PubMed  CAS  Google Scholar 

  • LeGrand, T. S., and Aw, T. Y., 1997, Chronic hypoxia, glutathione-dependent detoxication, and metabolic instability in rat small intestine, Am. J. Physiol. 272:G328–G334.

    PubMed  CAS  Google Scholar 

  • LeGrand, T. S., and Aw, T. Y., 1998, Chronic hypoxia alters glucose utilization during GSH-dependent detoxication in rat small intestine, Am. J. Physiol. 274:G376–G384.

    PubMed  CAS  Google Scholar 

  • Lifshitz, F, Wapnir, R. A., and Teichberg, S., 1986, Alterations in jejunal transport and (Na+-K+)-ATPase in an experimental model of hypoxia in rats, Proc. Soc. Exp. Biol. Med. 181:87–97.

    PubMed  CAS  Google Scholar 

  • Martensson, J., Jain, A., and Meister, A., 1990, Glutathione is required for intestinal function, Proc. Natl. Acad. Sci. USA 87:1715–1719.

    Article  PubMed  CAS  Google Scholar 

  • Masuda, Y., Ozaki, M., and Aoki, S., 1993, K+-driven sinusoidal efflux of glutathione disulfide under oxidative stress in the perfused rat liver, FEBS Lett. 334(1): 109–113.

    Article  PubMed  CAS  Google Scholar 

  • Mizoguchi, T., Morita, Y., Nanjo, H., Tereada, T., and Nishihara, T., 1994, Responses of glutathione-related enzymes in isolated rat small intestine to Fe2+-EDTA-mediated oxidative stress, Biol. Pharm. Bull. 17(5):607–611.

    Article  PubMed  CAS  Google Scholar 

  • Nagatsugawa, K., and Kaneda, T., 1983, Absorption and metabolism of methyl linoleate hydroperoxides in rats, J. Jpn. Oil Chem. Soc. 32:362–366.

    Google Scholar 

  • Parks, D. A., Bulkley, G. B., and Granger, D. N., 1983, Role of oxygen-derived free radicals in digestive tract diseases, Surgery 94:415–422.

    PubMed  CAS  Google Scholar 

  • Pritchard, P. J., and Porteous, J. W., 1977, Steady-state metabolism and transport of d-glucose by rat small intestine in vitro, Biochem. J. 164:1–14.

    PubMed  CAS  Google Scholar 

  • Reddy, B. S., 1983, Dietary fat and colon cancer, in: Experimental Colon Carcinogenesis (H. Antrup and G. M. Williams, eds.), CRC Press, Boca Raton, FL, pp. 225–239.

    Google Scholar 

  • Reddy, K., and Tappel, A. L., 1974, Effect of dietary selenium and autoxidized lipids on the glutathione peroxidse system of gastrointestinal tract and other tissues in the rat, J. Nutr. 104:1069–1078.

    PubMed  CAS  Google Scholar 

  • Sevanian, A., and Hochstein, P., 1985, Mechanisms and consequences of lipid peroxidation in biological systems, Ann. Rev. Nutr. 5:365–390.

    Article  CAS  Google Scholar 

  • Shan, X., Aw, T. Y., and Jones, D. P., 1990, Glutathione-dependent protection against oxidative injury, Pharmac. Ther 47:61–71.

    Article  CAS  Google Scholar 

  • Sies, H., 1985, Hydroperoxides and thiol oxidants in the study of oxidative stress in intact cells and organs, in: Oxidative Stress (H. Sies, ed.), Academic Press, Inc., London, pp. 73–90.

    Google Scholar 

  • Simic, M. G., and Karel, M., 1980, Autoxidation in Food and Biological Systems, Plenum Press, New York.

    Google Scholar 

  • Sridharan, K., Malhotra, M. S., Upadhayay, T. N., Grover, S. K., and Dua, G. L., 1982, Changes in gastrointestinal function in humans at an altitude of 3,500 m, Eur. J. Appl. Physiol. Occup. Physiol. 50:145–154.

    Article  CAS  Google Scholar 

  • Stoner, H. B., 1986, Metabolism after trauma and in sepsis, Circ. Shock 19:75–87.

    PubMed  CAS  Google Scholar 

  • Thurlbeck, W. M., Henderson, J. A., Fraser, R., and Bates, D. V., 1970, Chronic obstructive lung disease: A comparison between clinical, roentgenologic, functional, and morphological criteria in chronic bronchitis, emphysema, asthma, and bronchiectasis, Medicine 49:81–145.

    Article  Google Scholar 

  • Tribble, D. L., and Jones, D. P., 1990, Oxygen dependence of oxidative stress: Rate of NADPH supply for maintaining the GSH pool during hypoxia, Biochem. Pharmacol. 39(4):729–736.

    Article  PubMed  CAS  Google Scholar 

  • Uhlig, S., and Wendel, A., 1992, The physiological consequences of glutathione variations, Life Sct 51:1083–1094.

    Article  CAS  Google Scholar 

  • Van Liere, E. J., and Stickney, J. C., 1963, Hypoxia, The University of Chicago Press, Chicago.

    Google Scholar 

  • Verma, A. K., Ashenden, C. L., and Boutwell, R. K., 1980, Inhibition of prostaglandin synthesis inhibitors of the induction of epidermal ornithine decarboxylase activity, the accumulation of prostaglandin, and tumor promotion caused by 12-0-tetradecanoylphorbol-13-acetate, Canc. Res. 140:308–315.

    Google Scholar 

  • Vilas, N. N., Bell, R. R., and Draper, H. H., 1976, Influence of dietary peroxides, selenium, and vitamin E on glutathine peroxidase of the gastrointestinal tract, J. Nutr. 106:589–596.

    PubMed  CAS  Google Scholar 

  • Weigl, K., and Sies, H., 1977, Drug oxidations dependent on cytochrome P-450 in isolated hepatocytes: The role of the tricarboxylates and the aminotransferases in NADPH supply, Eur. J. Biochem. 77:401–408.

    Article  PubMed  CAS  Google Scholar 

  • Wendel, A., 1980, Glutathione peroxidase, in: Enzymatic Basis of Detoxication (W. B. Jakoby, ed.), Academic Press, New York, pp. 333–353.

    Google Scholar 

  • Wierzbicka, G. T., Hagen, T. M., and Jones, D. P., 1989, Glutathione in food, J. Food Compos. Anal. 2:327–337.

    Article  CAS  Google Scholar 

  • Williams, A. D., and Aw, T. Y., 1994, Glutathione (GSH) supply for lipid hydroperoxide metabolism in intestinal epithelial cells, Gastroenterol. 106(4): 1054.

    Google Scholar 

  • Wilson, T. H., and Wiseman, G., 1954, The use of sacs of everted small intestine for the study of the transference of substances from the mucosal to the serosal surface, J. Physiol. 123:116–125.

    PubMed  CAS  Google Scholar 

  • Wolff, S. P., and Nourooz-Zadeh, J., 1996, Hypothesis: UK consumption of dietary lipid hydroperoxides-A possible contributory factor to atherosclerosis, Atheroslerosis 119:261–263.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Respiratory Care, The University of Texas Health Science Center, San Antonio, Texas, 78245

    Terry S. LeGrand

  2. Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, Louisiana, 71130-3932

    Tak Yee Aw

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  1. Terry S. LeGrand
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Editors and Affiliations

  1. University of Tennessee College of Medicine, Memphis, Tennessee

    Charles M. Mansbach II

  2. University of Cincinnati College of Medicine, Cincinnati, Ohio

    Patrick Tso

  3. University of Toronto, Toronto, Ontario, Canada

    Arnis Kuksis

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LeGrand, T.S., Aw, T.Y. (2001). Intestinal Absorption and Metabolism of Peroxidized Lipids. In: Mansbach, C.M., Tso, P., Kuksis, A. (eds) Intestinal Lipid Metabolism. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1195-3_19

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