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The response of the antioxidant defense system in rat hepatocytes challenged with oxysterols is modified by Covi-ox

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Abstract

Suspension cultures of isolated rat hepatocytes were used to investigate whether 7-ketocholesterol and cholestane-3β,5α,6β-triol exert oxidative stress in cells as manifested by increased lipid peroxidation and the induction of the antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase. The oxysterols were found to increase the levels of both superoxide dismutase and catalase and to have variable effects on glutathione peroxidase activity. Increased lipid peroxidation was not observed, indicating that the endogenous antioxidant defense system was capable of protecting against any oxidative stress that might otherwise by exerted by 7-ketocholesterol or cholestane-3β,5α,6β-triol. Covi-ox, a natural tocopherol blend reduced the effects of both oxysterols on the antioxidant enzymes. A concurrent reduction in the production of thiobarbituric acid-reactive substances in Covi-ox-treated cells is indirect evidence that reactive oxygen species were produced by oxysterols in hepatocyte suspension cultures.

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References

  • Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121–6.

    Google Scholar 

  • Berry MN, Edwards AM. Isolated hepatocytes: preparation, properties and applications. Amsterdam: Elsevier; 1991.

    Google Scholar 

  • Blaauboer BJ. Hepatocyte cultures: properties and applications to toxicity testing. In: Kuiper HA, Hoogenboom LAP, eds. In vitro toxicological studies and real time analysis of residues in food. Wageningen: RIKILT-DLO; 1992:25–30. [Flair-Concerted Action No. 8]

    Google Scholar 

  • Blaauboer BJ, Boobis AR, Castell JV et al. The practical applicability of hepatocyte cultures in routine testing. ATLA. 1994;22:231–41.

    Google Scholar 

  • Emanuel HA, Hassel CA, Addis PB, Bergmann SD, Zavoral JH. Plasma cholesterol oxidation products (oxysterols) in human subjects fed a meal rich in oxysterols. J Food Sci. 1991;56:843–7.

    Google Scholar 

  • Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol. 1990;186b:407–21.

    Google Scholar 

  • Fanelli SL, Castro GD, Castro JA. Cholesterol interaction with free radicals produced from carbon tetrachloride or bromo-trichloromethane by either catalytic decomposition or via lipid microsomal activation. Chem-Biol Interact. 1995;98: 223–36.

    Google Scholar 

  • Gebhardt R. Multiple inhibitory effects of garlic extracts on cholesterol biosynthesis in hepatocytes. Lipids. 1993;28: 613–9.

    Google Scholar 

  • Gebhardt R. Protective antioxidant activity of extracts of artichokes in hepatic cells. Med Welt. 1995;46:393–5.

    Google Scholar 

  • Gebhardt R, Beck H. Differential inhibitory effects of garlic-derived organosulphur compounds on cholesterol biosynthesis in primary rat hepatocyte cultures. Lipids. 1996;31: 1269–76.

    Google Scholar 

  • Gelissen IC, Brown AJ, Mander EL, Kritharides L, Dean RT, Jessup W. Sterol efflux is impaired from macrophage foam cells selectively enriched with 7-ketocholesterol. J Biol Chem. 1996;271:17852–60.

    Google Scholar 

  • Gibson GG, Skett P. Introduction to drug metabolism. London: Blackie Academic and Professional; 1984.

    Google Scholar 

  • Huber KC, Pike OA, Huber CS. Antioxidant inhibition of cholesterol oxidation in a spray-dried food system during accelerated storage. J Food Sci. 1995;60:909–16.

    Google Scholar 

  • Imai H, Werthessen NT, Taylor CB, Lee KT. Angiotoxicity and arteriosclerosis due to contaminants of USP grade cholesterol. Arch Pathol Lab Med. 1976;100:565–72.

    Google Scholar 

  • Jacobson MS. Cholesterol oxides in Indian ghee: possible cause of unexplained high risk of atherosclerosis in Indian immigrant population. Lancet. 1987;II:656–8.

    Google Scholar 

  • Kowale BN, Rao VK, Babu NP, Sharma N, Bisht GS. Lipid oxidation and cholesterol oxidation in mutton during cooking and storage. Meat Sci. 1996;43:195–202.

    Google Scholar 

  • Khan SG, Katiyar SK, Agarwal R, Mukhtar H. Enhancement of antioxidant and phase II enzymes by oral feeding of green tea polyphenols in drinking water to SKH-1 hairless mice: possible role in chemoprevention. Cancer Res. 1992;52: 4050–2.

    Google Scholar 

  • Kumar N, Singhal OP. Cholesterol oxides and atherosclerosis: a review. J Sci Food Agric. 1991;58:267.

    Google Scholar 

  • Leist P, Raab B, Maurer S, Rosick U, Brigelius ?, Flohe R. Conventional cell culture media do not adequately supply cells with antioxidants and thus facilitate peroxide-induced genotoxicity. Free Radical Biol Med. 1996;21:297–306.

    Google Scholar 

  • Li SX, Ahn DU, Cherian G, Chung TY, Sim JS. Dietary oils and tocopherol supplementation on cholesterol oxide formation in freeze-dried chicken meat during storage. J Food Lipids. 1996;3:27–42.

    Google Scholar 

  • Mahfouz M, Smith T, Kummerow FA. Changes in linoleic acid metabolism and membrane fatty acids of LLC-PK cells in culture induced by 5alpha-cholestane-3beta,5,6-beta-triol. Lipids. 1995;30:977–85.

    Google Scholar 

  • Mak DH, Ip SP, Li PC, Poon MK, Ko KM. Effects of schisandrin B and alpha-tocopherol on lipid peroxidation, in vitro and in vivo. Mol Cell Biochem. 1996;165:161–5.

    Google Scholar 

  • McCluskey S, Connolly JF, Devery R et al. Lipid and cholesterol oxidation in whole milk powder during processing and storage. J Food Sci. 1997;62:331–7.

    Google Scholar 

  • Nielsen JH, Olsen CE, Lyndon J, Sorensen J, Skibsted LH. Cholesterol oxidation in feta cheese produced from high temperature bleached and from non-bleached butteroil from bovine. J Diary Res. 1996a;63:615–21.

    Google Scholar 

  • Nielsen JH, Olsen CE, Jensen C, Skibsted LH. Cholesterol oxidation in butter and dairy spread during storage. J Dairy Sci. 1996b;63:159–67.

    Google Scholar 

  • Ohtani K, Miyabara K, Okamoto E, Kamei M, Matsui Yuasa I. Cytotoxicity of 7-ketocholesterol towards cultured rat hepatocytes and the effect of vitamin E. Biosci Biotechnol Biochem. 1996;60:1989–93.

    Google Scholar 

  • Osada K, Kodama T, Noda S, Yamada K, Sugano M. Oxidised cholesterol modulates age-related change in lipid metabolism in rats. Lipids. 1995;30:405–13.

    Google Scholar 

  • Paniangvait P, King AJ, Jones AD, German BG. Cholesterol oxides in food of animal origin. J Food Sci. 1995;60:1159–74.

    Google Scholar 

  • Peng SK, Taylor CB, Safarik J, Mikkelson B. Arteriosclerosis induced by 25 hydroxycholesterol in squirrel monkeys. Fed Proc. 1982;41:452.

    Google Scholar 

  • Peng SK, Taylor CB, Hill JC, Morin RJ. Cholesterol oxidation derivatives and arterial endothelial damage. Atherosclerosis. 1985;54:121–33.

    Google Scholar 

  • Rice-Evans C. Antioxidant nutrients in protection against coronary heart disease and cancer. The Biochemist. 1995; 15:8–11.

    Google Scholar 

  • Rose-Sallin C, Huggett AC, Bosset J, Tabacchi R, Fay LB. Quantification of cholesterol oxidation products in milk powders using [2H7]cholesterol to monitor cholesterol autoxidation artifacts. J Agric Food Chem. 1995;43:935–41.

    Google Scholar 

  • Shozen K, Ohshima T, Ushio H, Koizumi C. Formation of cholesterol oxides in marine fish products induced by grilling. Fisheries Sci. 1995;61:817–21.

    Google Scholar 

  • Shozen K, Ohshima T, Ushio H, Takiguchi A, Koizumi C. Effects of antioxidants and packing on cholesterol oxidation in processed anchovy during storage. Food Sci Technol-Lebens-Wiss Technol. 1997;30:2–8.

    Google Scholar 

  • Stromstedt M, Rozman D, Waterman MR. The ubiquitously expressed human CYP51 encodes lanosterol 14 alpha-demethylase, a cytochrome P450 whose expression is regulated by oxysterols. Arch Biochem Biophys. 1996;329:73–81.

    Google Scholar 

  • Taylor CB, Peng SK, Werthesson NT, Tham P, Lee KT. Spontaneously occurring angiotoxic derivatives of cholesterol. Am J Clin Nutr. 1979;32:40–57.

    Google Scholar 

  • Vasavi H, Thangaraju M, Sachdanandam P. Effect of α-tocopherol on lipid peroxidation and antioxidant system in fibrosarcoma bearing rats. Mol Cell Biochem. 1994;131: 125–9.

    Google Scholar 

  • Verhagen JCD, terBraake P, Teunissen J, vanGinkel G, Sevanian A. Physical effects of biologically formed cholesterol oxidation products on lipid membranes investigated with fluorescence depolarisation spectroscopy and electron spin resonance. J Lipid Res. 1996;37:1488–502.

    Google Scholar 

  • Zunin P, Evangelisti F, Calcagno C, Tiscornia E. Cholesterol oxidation in dried egg pasta: detecting 7-ketocholesterol content. Cereal Chem. 1996;73:691–4.

    Google Scholar 

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  1. School of Biological Sciences, Dublin City University, Dublin, Ireland

    H. Cantwell & R. Devery

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  1. H. Cantwell
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  2. R. Devery
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Cantwell, H., Devery, R. The response of the antioxidant defense system in rat hepatocytes challenged with oxysterols is modified by Covi-ox. Cell Biol Toxicol 14, 401–409 (1998). https://doi.org/10.1023/A:1007595527176

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