Abstract
The effects of the phenolic compounds butylated hydroxytoluene (BHT), sesamin (S), curcumin (CU), and ferulic acid (FA) on plasma, liver, and lung concentrations of α- and γ-tocopherols (T), on plasma and liver cholesterol, and on the fatty acid composition of liver lipids were studied in male Sprague-Dawley rats. Test compounds were given to rats ad libitum for 4 wk at 4 g/kg diet, in a diet low but adequate in vitamin E (36 mg/kg of γ-T and 25 mg/kg of α-T) and containing 2 g/kg of cholesterol. BHT significantly reduced feed intake (P<0.05) and body weight and increased feed conversion ratio; S and BHT caused a significant enlargement of the liver (P<0.001), whereas CU and FA did not affect any of these parameters. The amount of liver lipids was significantly lowered by BHT (P<0.01) while the other substances reduced liver lipid concentrations but not significantly. Regarding effects on tocopherol levels, (i) feeding of BHT resulted in a significant elevation (P<0.001) of α-T in plasma, liver, and lung, while γ-T values remained unchanged; (ii) rats provided with the S diet had substantially higher γ-T levels (P<0.001) in plasma, liver, and lung, whereas α-T levels were not affected; (iii) administration of CU raised the concentration of α-T in the lung (P<0.01) but did not affect the plasma or liver values of any of the tocopherols; and (iv) FA had no effect on the levels of either homolog in the plasma, liver, or lung. The level of an unknown substance in the liver was significantly reduced by dietary BHT (P<0.001). BHT was the only compound that tended to increase total cholesterol (TC) in plasma, due to an elevation of cholesterol in the very low density lipoprotein + low density lipoprotein (VLDL+LDL) fraction. S and FA tended to lower plasma total and VLDL+LDL cholesterol concentrations, but the effect for CU was statistically significant (P<0.05). FA increased plasma high density lipoprotein cholesterol while the other compounds reduced it numerially, but not significantly. BHT, CU, and S reduced cholesterol levels in the liver TC (P<0.001) and percentages of TC in liver lipids (P<0.05). With regard to the fatty acid composition of liver lipids, S increased the n-6/n-3 and the 18∶3/20∶5 polyunsaturated fatty acids (PUFA) ratios, and BHT lowered total monounsaturated fatty acids and increased total PUFA (n−6+n−3). The effects of CU and FA on fatty acids were not highly significant. These results suggest some in vivo interactions between these phenolic compounds and tocopherols that may increase the bioavailability of vitamin E and decrease cholesterol in rats.
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Abbreviations
- BHT:
-
butylated hydroxytoluene
- CU:
-
curcumin
- FA:
-
ferulic acid
- GLM:
-
general linear model
- HDL:
-
high density lipoprotein
- HPLC:
-
high-performance liquid chromatography
- LDL:
-
low density lipoprotein
- PUFA:
-
polyunsaturated fatty acid
- S:
-
sesamin
- T:
-
tocopherol
- TC:
-
total cholesterol
- TMS:
-
trimethylsilyl
- TTP:
-
tocopherol transfer protein
- VLDL:
-
very low density lipoprotein
References
Huang, M.T., and Ferraro, T. (1992) Phenolic Compounds in Food and Cancer Prevention, in Phenolic Compounds in Food and their Effects on Health (II), pp. 8–34, American Chemical Society, Washington, DC.
Henn, T., and Stehle, P. (1998) [Total Phenolics and Antioxidant Activity of Commercial Wines, Teas and Fruit Juices], Ernährungs-Umschau 45, 308–313.
Bentsath, A., Rusznyak, S., and Szent-Györgi, A. (1936) Vitamin Nature of Flavones, Nature 138, 798.
Bentsath, A., Rusznyak, S., and Szent-Györgi, A. (1937) Vitamin P, Nature 139, 326–327.
Anonymous (1993) Inhibition of LDL Oxidation by Phenolic Substances in Red Wine: A Clue to the French Paradox?, Nutr. Rev. 51, 185–187.
Staley, L.L., and Mazier, M.J.P. (1999) Potential Explanation for the French Paradox, Nutr. Res. 19, 3–15.
Hoffman, R.M., and Garewal, H.S. (1995) Antioxidants and the Prevention of Coronary Heart Disease, Arch. Intern. Med. 155, 241–246.
Pace-Asciak, C.R., Hahn, R.S., Diamandis, E.P., Soleas, G., and Goldberg, D.M. (1995) The Red Wine Phenolics trans-Resveratrol and Quercetin Block Human Platelet Aggregation and Eicosanoid Synthesis: Implications for Protection Against Coronary Heart Disease, Clin. Chim. Acta 235, 207–219.
Harman, D. (1992) Free Radical Theory of Aging, Mutat. Res. 275, 257–266.
Guyton, K.Z., and Kensler, T.W. (1993) Oxidative Mechanisms in Carcinogenesis, Br. Med. Bull. 49, 523–544.
Bartsch, H., Ohshima, H., and Pignatelli, B. (1988) Inhibitors of Endogenous Nitrosation: Mechanisms and Implications in Human Cancer Prevention, Mutat. Res. 202, 307–324.
Shahidi, F., Janitha, P.K., and Wanasundara, P.D. (1992) Phenolic Antioxidants, Crit. Rev. Food Sci. Nutr. 32, 67–103.
Steinberg, D., Parthasarathy, S., Carew, T.E., Khoo, J.C., and Witztum, J.L. (1989) Beyond Cholesterol, Modifications of Low-density Lipoprotein That Increase Its Atherogenity, New Engl. J. Med. 320, 915–924.
Ikeda, I., Imasato, Y., Sasaki, E., Nakayama, M., Nagao, H., Takeo, T., Yayabe, F., and Sugano, M. (1992) Tea Catechins Decrease Micellar Solubility and Intestinal Absorption of Cholesterol in Rats, Biochem. Biophys. Acta 1127, 141–146.
Hirose, N., Inoue, T., Nishihara, K., Sugano, M., Akimoto, K., Shimizu, S., and Yamada, H. (1991) Inhibition of Cholesterol Absorption and Synthesis in Rats by Sesamin, J. Lipid Res. 32, 629–638.
Agarwal, R., Wang, Z.Y., Bik, D.P., and Mukhtar, H. (1991) Nordihydro-Guariaretic Acid, an Inhibitor of Lipoxygenase, Also Inhibits Cytochrome P-450-Mediated Mono-Oxygenase Activity in Rat Epidermal and Hepatic Microsomes, Drug. Metab. Dispos. 19, 620–624.
Alanko, J., Riutta, A., Mucha, T., Vapaatalo, H., and Metsa-Ketela, T. (1993) Modulation of Arachidonic Acid Metabolism by Phenols: Relation to Positions of Hydroxyl Groups and Peroxyl Radical Scavenging Properties, Free Radical-Biol. Med. 14, 19–25.
Laughton, M.J., Evans, P.J., Moroney, M.A., Hoult, J.R., and Halliwell, B. (1991) Inhibition of Mammalian 5-Lipoxygenase and Cyclo-Oxygenase by Flavonoids and Phenolic Dietary Additives. Relationship to Antioxidant Activity and to Iron Ion-Reducing Ability, Biochem. Pharmacol. 42, 1673–1681.
Mazur, W., and Adlercreutz, H. (1998) Natural and Anthropogenic Environmental Oestrogens: The Scientific Basis for Risk Assessment, Pure Appl. Chem. 70, 1759–1776.
The ATBC Cancer Prevention Study Group (1994) The Effect of Vitamin E and β-Carotene on the Incidence of Lung Cancer and Other Cancers in Male Smokers, New Engl. J. Med. 330, 1029–1035.
Chan, A.C. (1998) Vitamin E and Atherosclerosis, J. Nutr. 128, 1593–1596.
Takahata, K., Monobe, K., Tada, M., and Weber, P.C. (1998) The Benefits and Risks of n-3 Polyunsaturated Fatty Acids, Biosci. Biotechnol. Biochem. 62, 2079–2085.
Willett, W.C. (1998) The Dietary Pyramid: Does the Foundation Need Repair? Am. J. Clin. Nutr. 68, 218–219.
Pietinen, P., Rimm, E.B., Korhonen, P., Hartman, A.M., Willett, W.C., Albanes, D., and Virtamo, T.J. (1996) Intake of Dietary Fiber and Risk of Coronary Heart Disease in a Cohort of Finnish Men: The α-Tocopherol, β-Carotene Cancer Prevention Study, Circulation 94, 2720–2727.
Yamashita, K., Nohara, Y., Katayama, K., and Namiki, M. (1992) Sesame Seed Lignans and α-Tocopherol Act Synergistically to Produce Vitamin E Activity in Rats, J. Nutr. 122, 2440–2446.
Kamal-Eldin, A., Pettersson, D., and Appelqvist, L.Å. (1995) Sesamin (a compound from sesame oil) Increases Tocopherol Levels in Rats Fed ad libitum, Lipids 30, 499–505.
Yamashita, K., Iizuka, Y., Imai, T., and Namiki, M. (1995) Sesame Seed and Its Lignans Produce Marked Enhancement of Vitamin E Activity in Rats Fed a Low α-Tocopherol Diet, Lipids 30, 1019–1028.
Nardini, M., Natella, F., Gentili, V., Di Felice, M., and Scaccini, C. (1997) Effect of Caffeic Acid Dietary Supplementation on the Antioxidant Defense System in Rat: An in vivo Study, Arch. Biochem. Biophys. 342, 157–160.
Hara, A., and Radin, N.S. (1978) Lipid Extraction of Tissues with a Low-Toxicity Solvent, Anal. Biochem. 90, 420–426.
Seigler, L., and Wu, W.T. (1981) Separation of Serum High-Density Lipoprotein for Cholesterol Determination: Ultracentrifugation vs. Precipitation with Sodium Phosphotungstate and Magnesium Chloride, Clin. Chem. 27, 838–841.
SAS® (1988) User's Guide: Statistics version 6.03 Edition, SAS Institute, Inc., Cary, NC.
Srinivasan, M.R., and Satyanarayana, M.N. (1988) Influence of Capsaicin, Eugenol, Curcumin and Ferulic Acid on Sucrose-Induced Hypertriglyceridemia in Rats, Nutr. Reports Intern. 38, 571–581.
Kahl, R., and Kappus, H. (1992) [Toxicology of the Synthetic Antoxidants BHA and BHT in Comparison with the Natural Antioxidant Vitamin-E], Z. Lebensm. Unters. Forsch. 196, 329–338.
Takahashi, O., and Hiraga, K. (1981) Effect of Butylated Hydroxytoluene on the Lipid Composition of Rat Liver, Toxicology 22, 161–170.
Sugano, M., Inoue, T., Koba, K., Yoshida, K., Hirose, N., Shinmen, Y., Akimoto, K., and Amachi, T. (1990) Influence of Sesame Lignans on Various Lipid Parameters in Rats, Agric. Biol. Chem. 54, 2669–2673.
Sugano, M., and Akimoto, K. (1993) Sesamin: A Multifunctional Gift from Nature, J. Chinese Nutr. Soc. 18, 1–11.
Nakabayashi, A., Kitagawa, Y., Suwa, Y., Akimoto, K., Asami, S., Shimizu, S., Hirose, N., Sugano, M., and Yamada, H. (1995) α-Tocopherol Enhances the Hypocholesterolemic Action of Sesamin in Rats, Int. J. Vit. Nutr. Res. 65, 162–168.
Yamamoto, K., Fukuda, N., Shiroi, S., Yoshida, K., Hirose, N., Shinmen, Y., Akimoto, K., and Amachi, T. (1995) Effect of Dietary Antioxidants on the Susceptibility to Hepatic Microsomal Lipid Pperoxidation in the Rat, Ann. Nutr. Metabol. 39, 99–106.
Simán, C.M., and Eriksson, U.J. (1996) Effect of Butylated Hydroxytoluene on α-Tocopherol Content in Liver and Adipose Tissue of Rats, Toxicol. Lett. 87, 103–108.
Subba Rao, D., Chandra Sekhara, N., Satyanarayana, N., and Srinivasan, M. (1970) Effect of Curcumin on Serum and Liver Cholesterol Levels in the Rat, J. Nutr. 100, 1307–1316.
Satchithanandam, S., Chanderbhan, R., Kharroubi, A.T., Calvert, R.J., Klurfeld, D., Tepper, S.A., and Kritchevsky, D. (1996) Effect of Sesame Oil on Serum and Liver Lipid Profiles in the Rat, Int. J. Vit. Nutr. Res. 66, 386–392.
Bieri, J.G., and Evarts, R.P. (1974) Vitamin E Activity of α-Tocopherol in the Rat, Chick and Hamster, J. Nutr. 104, 850–857.
Bieri, J.G., and Evarts, R.P. (1974) Gamma Tocopherol: Metabolism, Biological Activity and Significance in Human Vitamin E Nutrition, Am. J. Clin. Nutr. 27, 980–986.
Leth, T., and Søndergaard, H. (1977) Biological Activity of Vitamin E Compounds and Natural Materials by the Resorption-Gestation Test, and Chemical Determination of the Vitamin E Activity in Foods and Feeds, J. Nutr. 107, 2236–2243.
Tran, K., and Chan, A.C. (1992) Comparative Uptake of α- and γ-Tocopherol by Human Endothelial Cells, Lipids 27, 38–41.
Kayden, H.J., and Traber, M.G. (1993) Absorption, Lipoprotein Transport, and Regulation of Plasma Concentrations of Vitamin E in Humans, J. Lipid Res. 34, 343–358.
Sato, Y., Hagiwara, K., Arai, H., and Inoue, K. (1991) Rurification and Characterization of the α-Tocopherol Transfer Protein from Rat Liver, FEBS Lett. 288, 41–45.
Arita, M., Nomura, K., Arai, H., and Inoue, K. (1997) α-Tocopherol Transfer Protein Stimulates the Secretion of α-Tocopherol from a Cultured Liver Cell Line Through a Brefeldin A-Insensitive Pathway, Proc. Natl. Acad. Sci. USA 94, 12437–12441.
Hosomi, A., Arita, M., Sato, Y., Kiyose, C., Ueda, T., Igarashi, O., Arai, H., and Inoue, K. (1997) Affinity for α-Tocopherol Transfer Protein as a Determinant of the Biological Activities of Vitamin E Analogs FEBS Lett. 409, 105–108.
Traber, M.G., and Kayden, H.J. (1989) Preferential Incorporation of α-Tocopherol vs. γ-Tocopherol in Human Lipoproteins, Am. J. Clin. Nutr. 49, 517–526.
Bjorneboe, A., Bjorneboe, G.E., and Drevon, C.A. (1987) Serum Half-Life, Distribution, Hepatic Uptake and Biliary Excretion of α-Tocopherol in Rats, Biochim. Biophys. Acta 921, 175–181.
Chiku, S., Hamamura, K., and Nakamura, T. (1984) Novel Urinary Metabolite of d-δ-Tocopherol in Rats, J. Lipid Res. 25, 40–48.
Schonfeld, A., Schultz, M., Petrzika, M., and Gassmann, B. (1993) A Novel Metabolite of RRR-α-Tocopherol in Human Urine, Nahrung 37, 498–500.
Schultz, M., Leist, M., Petrzida, M., Gassmann, B., and Brigelius-Flohe, R. (1995) A Novel Urinary Metabolite of α-Tocopherol: 2,5,7,8-Tetramethyl-2(2′-carboxyethyl)-6-hydroxychroman (α-CEHC) as an Indicator of an Adequate Vitamin E Supply? Am. J. Clin. Nutr. 62 (Suppl), 1527S-1543S.
Swanson, J.E., Ben, R.N., Burton, G.W., and Parker, R.S. (1999) Urinary Excretion of 2,7,8-Trimethyl-2-(β-carboxyethyl)-6-hydroxychroman Is a Major Route of Elimination of γ-Tocopherol in Humans, J. Lipid Res. 40 665–671.
Casida, J.E. (1970) Mixed Function Oxidase Involvement in the Biochemistry of Insecticidal Synergists, J. Agric. Food Chem. 18, 753–772.
Mustacich, D.J., Shields, J., Horton, R.A., Brown, M.K., and Reed, D.J. (1998) Biliary Secretion of α-Tocopherol and the Role of the mdr2 P-Glycoprotein in Rats and Mice, Arch. Biochem. Biophys. 350, 183–192.
Mustacich, D.J., Brown, M.K., and Reed, D.J. (1996) Colchicine and Vinblastine Prevent the Piperonyl Butoxide-Induced Increase in Rat Biliary Output of α-Tocopherol, Toxicol. Applied Pharmacol. 139, 411–417.
Joint Industrial Safety Council (1997) Chemical Substances, CD-ROM ISBN 91-7522-551-4, Joint Industrial Safety Council, Stockholm.
Björkhem, I., Henriksson-Freyschuss, A., Breuer, O., Diczfalusy, U., Berglund, L., and Henriksson, P. (1991) The Antioxidant Butylated Hydroxytoluene Protects Against Atherosclerosis, Atheroscler. Thromb. 11, 15–22.
Leblanc, G., and Gillette, I.S. (1993) Elevation of Serum Cholesterol Levels in Mice by the Antioxidant Butylated Hydroxyanisole, Biochem. Pharmacol. 45, 513–515.
Tamizhselvi, R., Samikkannu, T., and Niranjali, S. (1995) Pulmonary Phospholipid Changes Induced by Butylated Hydroxy Toluene, an Antioxidant, in Rats, Ind. J. Exper. Biol. 33, 796–797.
Hirata, F., Fujita, K., Ishikura, Y., Hosoda, K., Ishikawa, T., and Nakamura, H. (1995) Hypocholesteremic Effect of Sesame Lignan in Humans, Atherosclerosis 122, 135–136.
Patil, T.N., and Srinivasan, M. (1971) Hypocholesteremic Effect of Curcumin in Induced Hypercholesterolemic Rats, Ind. J. Exper. Biol. 9, 167–169.
Seetharamaiah, G.S., and Chandrasekhara, N. (1990) Effect of Oryzanol on Cholesterol Absorption and Biliary and Fecal Bile Acids in Rats, Ind. J. Med. Res. [B] 92, 471–475.
Igarashi, O., Umeda-Sawada, R., and Fujiyama-Fujiwara, Y. (1995) Effect of Dietary Factors on the Metabolism of Essential Fatty Acids: Focusing on the Components of Spices, in Nutrition, Lipids, Health and Disease (Ong, A.S.H., Niki, E. and Packer, L., eds.), pp. 59–66, AOCS Press, Champaign.
Shimizu, S., Akimoto, K., Shinmen, Y., Kawashima, H., Sugano, M., and Yamada, H. (1991) Sesamin Is a Potent and Specific Inhibitor of Δ5 Desaturase in Polyunsaturated Fatty Acid Biosynthesis, Lipids 26, 512–516.
Dwyer, J.T. (1988) Health Aspects of Vegetarian Diets, Am. J. Clin. Nutr. 48 (suppl.), 712–738.
Steinmetz, K.A., and Potter, J.D. (1991) Vegetables, Fruits and Cancer. II. Mechanisms, Cancer Causes Control 1, 427–442.
Block, G., Patterson, B., and Subar, A. (1992) Fruit, Vegetables and Cancer Prevention: A Review of the Epidemiological Evidence, Nutr. Cancer 18, 1–29.
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Kamal-Eldin, A., Frank, J., Razdan, A. et al. Effects of dietary phenolic compounds on tocopherol, cholesterol, and fatty acids in rats. Lipids 35, 427–435 (2000). https://doi.org/10.1007/s11745-000-541-y
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DOI: https://doi.org/10.1007/s11745-000-541-y