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Effect of Hesperidin Supplementation on Lipid and Antioxidant Metabolism in Ethanol-fed Rats

  • Kim, Soon-Ja (Department of Oral and Maxillofacial Surgery, Seoul National University) ;
  • Seo, Hyun-Ju (Department of Food Science and Nutrition, Kyungpook National University) ;
  • Kim, Hye-Jin (Department of Food Science and Nutrition, Kyungpook National University) ;
  • Cho, Yun-Young (Department of Food Science and Nutrition, Kyungpook National University) ;
  • Kwon, Eun-Young (Department of Food Science and Nutrition, Kyungpook National University) ;
  • Lee, Hyo-Sun (Department of Chemistry, Kyungpook National University) ;
  • Choi, Myung-Sook (Department of Food Science and Nutrition, Kyungpook National University)
  • Published : 2006.12.01

Abstract

This study examined the effect of hesperidin supplementation with an ethanol diet on lipid and antioxidant metabolism in rats. Male Sprague-Dawley rats were divided into two groups (n=10), and were assigned to one of two dietary categories: $E_8$, ethanol diet (50 g/L) for 8 wks; $E_8H_4$, ethanol diet for the first 4 wks and hesperidin (0.02%, w/w) supplemented ethanol diet for the last 4 wks. The plasma and hepatic lipids, hepatic cholesterol regulating enzyme activity, hepatic antioxidant enzyme activity and lipid peroxidation were determined. Supplementation with hesperidin for the last 4 wks during the 8 wks period of the ethanol diet, significantly increased the ADH activity. In conjunction with the chronic administration of ethanol, hesperidin supplementation resulted in a significant decrease in the hepatic cholesterol and triglyceride concentrations compared to the $E_8$ group. The hepatic HMG-CoA reductase and ACAT activities were significantly lower in the hesperidin-supplemented group. When comparing hepatic antioxidant enzyme activities, SOD, GSH-Px, and G6PD activities and GSH level were significantly higher in the $E_8H_4$ group than in the E8 group. Plasma TBARS levels were significantly lower in rats fed ethanol with hesperidin compared to the rats fed only ethanol; however, the hepatic TBARS levels were not significantly different between the groups. Accordingly, the additional hesperidin supplement with an ethanol diet might be effective for improving the hepatic lipid metabolism and antioxidant defense system.

Keywords

References

  1. Lee HC, Lee HS, Jung SH, Yi SY, Jung HK, Yoon JH, Kim CY. 2001. Association between polymorphisms of ethanol-metabolizing enzymes and susceptibility to alcoholic cirrhosis in a Korean male population. J Korean Med Sci 16: 745-750 https://doi.org/10.3346/jkms.2001.16.6.745
  2. Bunout D. 1999. Nutritional and metabolic effects of alcoholism: their relationship with alcoholic liver disease. Nutrition 15: 583-589 https://doi.org/10.1016/S0899-9007(99)00090-8
  3. Crawford DW, Blankenhorn DH. 1991. Arterial wall oxygenation, oxyradicals and atherosclerosis. Atherosclerosis 89: 97-108 https://doi.org/10.1016/0021-9150(91)90049-9
  4. Middleton E Jr, Drezewiecki G. 1984. Flavonoid inhibition of human basophil histamine release stimulated by various agents. Biochem Pharmacol 1: 3333-3338
  5. Pietta PG. 2000. Flavonoids as antioxidants. J Nat Prod 63: 1035-1042 https://doi.org/10.1021/np9904509
  6. Kuhnau J. 1976. The flavonoids. A class of semi-essential food components: their role in human nutrition. World Rev Nut Diet 24: 117-123
  7. Garg A, Garg S, Zaneveld LJD, Singla AK. 2001. Chemistry and pharmacology of the citrus bioflavonoid hesperidin. Phytother Res 15: 655-669 https://doi.org/10.1002/ptr.1074
  8. Chiba H, Uehara M, Wu J, Wang X, Masuyama R, Suzuki K, Kanazawa K, Ishimi Y. 2003. Hesperidin, a citrus flavonoid, inhibits bone loss and decreases serum and hepatic lipids in ovariectomized mice. J Nutr 133: 1892-1897
  9. Zhang M, Zhang JP, Ji HT, Wang JS, Qian DH. 2000. Effect of six flavonoids on proliferation of hepatic stellate cells in vitro. Acta Pharmacol Sin 21: 253-256
  10. Borradaile NM, Carroll KK, Kurowska EM. 1999. Regulation of HepG2 cell apolipoprotein B metabolism by the citrus flavanones hesperetin and naringenin. Lipids 34: 591-598 https://doi.org/10.1007/s11745-999-0403-7
  11. Dinu V, Zanfir D. 1991. Oxidative stress in ethanol intoxicated rats. Revue Roumainme de Physiologie 28: 63-67
  12. Dianzani NU. 1987. The role of free radical in liver damage. Proce Nutr Soc 46: 43-52
  13. Strubelt O, Younes M, Pentz R. 1987. Enhancement by gluthathione depletion of ethanol-induced acute hepatotoxicity in vitro and in vivo. Toxicology 45: 231-223
  14. Lieber CS, DeCarli LM. 1986. The feeding of ethanol in liquid diets: 1986 update. Alcohol Clin Exp Res 10: 550-553 https://doi.org/10.1111/j.1530-0277.1986.tb05140.x
  15. Allain CC, Poon LS, Chen CSG, Richmond W, Fu PC. 1974. Enzymatic determination of total serum cholesterol. Clin Chem 20: 470-475
  16. Warnick GR, Albers JJ. 1978. A comprehensive evaluation of the heparin manganease precipitation procedure for estimating a high density lipoprotein cholesterol. J Lipid Res 19: 65-76
  17. McGrowan MW, Artiss JD, Strandbergh DR, Zak B. 1983. A peroxidase-coupled method for the colorimetric determination of serum triglycerides. Clin Chem 29: 538-542
  18. Folch J, Lees M, Sloan-Stanley GH. 1957. A simple method for isolation and purification of total lipids from animal tissues. J Biol Chem 226: 497-509
  19. Tarladgis BG, Pearson AM, Duran LR. 1964. Chemistry of the 2-thio-barbituric acid test for determination of oxidative rancidity in foods. J Sci Food Agri 15: 602-607 https://doi.org/10.1002/jsfa.2740150904
  20. Ohkawa H, Ohishi N, Yagi K. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95: 351-358 https://doi.org/10.1016/0003-2697(79)90738-3
  21. Abei H. 1974. Catalase. In Method of Enzymatic Analysis. Academic Press Inc, New York. Vol II, p 673-684
  22. Marklund S, Marklund G. 1974. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47: 469-474 https://doi.org/10.1111/j.1432-1033.1974.tb03714.x
  23. Paglia ED, Valentine WN. 1979. Studies on the quantitative and qualitative characterization of erythrocytes glutathione peroxidase. J Lab Clin Med 70: 158-169
  24. Bradford MM. 1976. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248-254 https://doi.org/10.1016/0003-2697(76)90527-3
  25. Pinto RE, Bartley W. 1969. The effect of age and sex on glutathione reductase and glutathione peroxidase activities and on aerobic glutathione oxidation in rat liver homogenates. Biochem J 112: 109-115 https://doi.org/10.1042/bj1120109
  26. Pitkanen E, Pitkanen O, Uotil L. 1997. Enzymatic determination of unbound D-mannose in serum. Eur J Clin Chem Clin Biochem 35: 761-766
  27. Bergmeyer HU. 1974. Methods of Enzymatic Analysis. Academic Press, New York. Vol III, p 1314-1319
  28. Koivula T, Koivusalo M. 1975. Different form of rat liver aldehyde dehydrogenase and their subcellular distribution. Biochimica et Biophysica Acta 397: 9-23 https://doi.org/10.1016/0005-2744(75)90174-6
  29. Ellman GL. 1959. Tissue sulfhydryl group. Arch Biochem Biopsy 82: 70-77 https://doi.org/10.1016/0003-9861(59)90090-6
  30. Hulcher FH, Oleson WH. 1973. Simplified spectrophotometric assay for microsomal 3-hydroxy-3-methylglutaryl CoA reductase by measurement of coenzyme A. J Lipid Res 14: 625-631
  31. Bradford MM. 1979. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Bioche 72: 248-254
  32. Shapiro DJ, Nordstrom JL, Mitschelen JJ, Rodwell VW, Schimke RT. 1974. Micro assay for 3-hydroxy-3-methylglutaryl CoA reductase in rat liver and in L-cell fibroblasts. Biochim Biophys Acta 370: 369-377 https://doi.org/10.1016/0005-2744(74)90098-9
  33. Erickson SK, Schrewsbery MA, Brooks C, Meyer DJ. 1980. Rat liver acyl-coenzyme A:cholesterol acyltransferase: its regulation in vivo and some of properties in vitro. J Lipid Res 21: 930-941
  34. Gillies PJ, Rathgeb KA, Perri MA, Robinson CS. 1986. Regulation of acyl-CoA:cholesterol acyltransferase activity in normal and atherosclerotic rabbit aortas: role of a cholesterol substrate pool. Exp Mol Pathol 44: 329-339 https://doi.org/10.1016/0014-4800(86)90046-8
  35. Lieber CS. 1991. Hepatic metabolic and toxic effects of ethanol: 1991 update. Alcohol Clin Exp Res 15: 573- 592 https://doi.org/10.1111/j.1530-0277.1991.tb00563.x
  36. Lieber CS. 2001. Alcoholic liver injury: pathogenesis and therapy in 2001. Pathol Biol 49: 738-752 https://doi.org/10.1016/S0369-8114(01)00239-5
  37. Bok SH, Lee SH, Park YB, Bae KH, Son KH, Jeong TS, Choi MS. 1999. Plasma and hepatic cholesterol and hepatic activities of 3-hydroxy-3-methyl-glutaryl-CoA reductase and acyl CoA:cholesterol transferase are lower in rats fed citrus peel extract or a mixture of citrus bioflavonoids. J Nutr 129: 1182-1185
  38. Alberts AW, Chen J, Kuron G, Hunt V, Huff J, Hoffman C, Rothrock J, Lopez M, Joshua H, Harris E, Patchett A, Monaghan R, Currie S, Stapley E, Albers- Schonberg G, Hensens O, Hirshfield J, Hoogsteen K, Liesch J, Springer J. 1980. Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc Natl Acad Sci 77: 3957-3961
  39. Billheimer DW, Grundy SM, Brown MS, Goldstein JL. 1983. Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. Proc Natl Acad Sci USA 80: 4124-4128
  40. Helgerud P, Saarem K, Norum KR. 1981. Acyl-CoA: cholesterol acyltransferase in human small intestine: its activity and some properties of the enzyme reaction. J Lipid Res 22: 271-277
  41. Sucking KE, Stange EF. 1985. Role of acyl-CoA:cholesterol acyl transferase in cellular cholesterol metabolism. J Lipid Res 26: 647-671
  42. Brown MS, Ho YK, Goldstein JL. 1980. The cholesterol ester cycle in mactophage foam cells. Continual hydrolysis and reesterification of cytoplasmic cholesteryl esters. J Biol Chem 255: 9344-9352
  43. Wilcox LJ, Borradaile NM, Dreu de LF, Huff MW. 2001. Secretion of hepatpcyte apoB is inhibited be the flavonoids, naringenin and hesperetin, via reduced activity and expression of ACAT2 and MTP. J Lipid Res 42: 725-734
  44. Borradaile NM, Caroll KK, Kurowska EM. 1999. Regulation of hepG2 cell apolipoprotein B metabolism by the citrus flavanones hesperetin and naringenin. Lipids 34: 591-598 https://doi.org/10.1007/s11745-999-0403-7
  45. Suter PM, Gerritsen-Zehnder M, Ha¨sler E, Gurtler M, Vetter W, Hanseler E. 2001. Effect of alcohol on postprandial lipemia with and without preprandial exercise. J Am Coll Nutr 20: 58-64 https://doi.org/10.1080/07315724.2001.10719015
  46. Kakkar R, Kalra J, Mantha SV, Prasad K. 1995. Lipid peroxidation and activity of antioxidant enzymes in diabetic rats. Mol Cell Biochem 151: 113-119 https://doi.org/10.1007/BF01322333
  47. Thampi HBS, Manoj G, Leelamma S, Menon VP. 1991. Dietary fiber and lipid peroxidation. Effects of dietary fiber on levels of lipids and lipid peroxides in high fat diet. Ind J Exp Biol 29: 563-567
  48. Sheela CG, Angusti KT. 1992. Antiperoxide effects of Sallyl cystein sulphoxide isolated from garlic Allium sativum Linn. Indian J Exp Biol 30: 523-526
  49. Reedy ACP, Lokesh BP. 1992. Studies on spice principles as antioxidants in the inhibition of lipid peroxidation of rat liver microsomes. Mol Cell Biochem 111: 117-124
  50. Antonekov AD, Panchenko LF. 1988. Effect of chronic ethanol treatment under partial catalase inhibition on the activity of enzymes related to peroxide metabolism in rat liver and heart. Int J Biochem 20: 823-828 https://doi.org/10.1016/0020-711X(88)90071-7
  51. Pigeolot E, Cornisier P, Houbion A, Lambert D, Michiels C, Raes M, Zachary MD, Remacle J. 1990. Glutathione peroxidase, superoxide dismutase and catalase inactivation by peroxide and oxygen derived radicals. Mech Ageing Dev 51: 283-97 https://doi.org/10.1016/0047-6374(90)90078-T
  52. Santiard D, Ribiere C, Nordmann R, Houze-Levin C. 1995. Inactivation of Cu, Zn-superoxide dismutase by free radicals derived from ethanol metabolism: a${\gamma}$-radiolysis study. Free Radic Biol Med 19: 121-127 https://doi.org/10.1016/0891-5849(95)00008-L
  53. Frank L, Messaro D. 1980. Oxygen toxicity. Am J Med 69: 117–126 https://doi.org/10.1016/0002-9343(80)90509-4
  54. Doroshow JH, Locker GY, Myers CE. 1980. Enzymatic defenses of the mouse heart against reactive oxygen metabolites: alterations produced by doxorubicin. J Clin Invest 65: 128-135 https://doi.org/10.1172/JCI109642
  55. Gueeri H. 1995. Influence on prolonged ethanol intake on the level and turnover of alcohol and aldehyde degydrogenase and glutathione. Adv Exp Med Biol 23: 12-14
  56. Shaw S, Rubin KP, Lieber CS. 1983. Depressed hepatic glutathione and increased zinc conjugates in alcoholic liver disease, evidence of lipid peroxidation. Dig Dis Sci 7: 585-589
  57. Speisky H, MacDonald A, Giles G, Orrego H, Israel Y. 1985. Increased loss and decreased synthesis of hepatic glutathione after acute ethanol administration. Biochem J 225: 565-572 https://doi.org/10.1042/bj2250565
  58. Anand CV, Anand V, Agarwal R. 1996. Antioxidant enzymes, gamma glutamyl transpeptidase and lipid peroxidation in kidney of rats exposed to cigarette smoke. Indian J Exp Biol 34: 486-488
  59. Gallagher EP, Buetler TM, Stapleton P, Wang C, Stahl DL, Eaton DL. 1995. The effects of diquat and ciprofibrate mRNA experession and catalytic activities of hepatic xenobiotic metabolizing and antioxidant enzyme in rat liver. Toxicol Appl Pharmacol 134: 81-91 https://doi.org/10.1006/taap.1995.1171
  60. Shaw S, Jayatilleke E, Ross WA, Gordon ER, Lieber CS. 1981. Ethanol-induced lipid peroxidation, potentiation by long-term alcohol feeding and attenuation by methionine. J Lab Clin Med 987: 417-424
  61. Szweda LI, Uchida K, Tasi L, Stadtman ER. 1993. Inactivation of glucose-6-phosphate dehydrogenase by 4-hydroxy-2-nonenal. J Biol Chem 268: 3342-3347
  62. Oh SI, Kim CI, Chun HJ, Park SC. 1998. Chronic ethanol consumption affects glutathione status in rat liver. J Nutr 128: 758-763

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