J Appl Biomed 10:91-101, 2012 | DOI: 10.2478/v10136-011-0014-3

Modulation of antioxidant enzymes activities and lipid peroxidation products in diet-induced hypercholesterolemic rats fed ortanique peel polymethoxylated flavones extract

Curtis Omar Green1,2,*, Andrew O'Brien Wheatley2,3, Donovan Anthony McGrowder4, Lowell Lloyd Dilworth2, Helen Nosakhare Asemota2,3
1 Tropical Medicine Research Institute, University of the West Indies, Kingston, Jamaica
2 Department of Basic Medical Sciences (Biochemistry Section), University of the West Indies, Kingston, Jamaica
3 Biotechnology Centre, University of the West Indies, Kingston, Jamaica
4 Department of Pathology, University of the West Indies, Kingston, Jamaica

The primary aim of this study was to investigate the effects of ortanique peel polymethoxylated flavones extract (PMFort) on antioxidant enzymes activities and lipid peroxide levels in organs of hypercholesterolemic and normal rats. Thirty Sprague-Dawley rats were fed high cholesterol diets supplemented with 1.5% PMFort and niacin respectively for 49 days. Hypercholesterolemic rats fed PMFort had significant reductions in malondialdehyde levels in the liver and brain compared to untreated hypercholesterolemic control rats. This reduction also occurred in the brain of the rats fed niacin. The activities of catalase, glutathione reductase, transferase and peroxidase were significantly reduced in the spleen, brain and liver of hypercholesterolemic rats fed PMFort compared to control. The activities of these enzymes were only reduced in the brain and liver of rats fed niacin. The results would suggest that PMFort modulates hypercholesterolemia-associated organ injury and oxidative stress in rat organs. PMFort could therefore be a suitable candidate of natural origin for prophylactic and therapeutic treatment of hypercholesterolemia-associated oxidative stress and organ injury.

Keywords: hypercholesterolemia; ortanique; antioxidant enzymes; polymethoxylated flavones

Received: August 3, 2011; Revised: September 7, 2011; Published: July 31, 2012  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Green CO, Wheatley AO, McGrowder DA, Dilworth LL, Asemota HN. Modulation of antioxidant enzymes activities and lipid peroxidation products in diet-induced hypercholesterolemic rats fed ortanique peel polymethoxylated flavones extract. J Appl Biomed. 2012;10(2):91-101. doi: 10.2478/v10136-011-0014-3.
Download citation

References

  1. Affany A, Salvayre R, Douste-Blazy L. Comparison of the protective effect of various flavonoids against lipid peroxidation of erythrocyte membranes (induced by cumene hydroperoxide). Fundam Clin Pharmacol. 1: 451-457, 1987. Go to original source... Go to PubMed...
  2. Beers RF, Jr., Sizer IW. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem. 195: 133-140, 1952. Go to original source...
  3. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 72: 248-254, 1976. Go to original source... Go to PubMed...
  4. Carlberg I, Mannervik B. Glutathione reductase assay. In Colowick SP, Kaplan NO (eds.): Methods in Enzymology, vol. 113. Academic Press, Orlando, FL, pp. 484-495, 1985. Go to original source...
  5. Chade AR, Rodriguez-Porcel M, Grande JP, Krier JD, Lerman A, Romero JC, Napoli C, Lerman LO. Distinct renal injury in early atherosclerosis and renovascular disease. Circulation. 106: 1165-1171, 2002. Go to original source... Go to PubMed...
  6. Chade AR, Krier JD, Galili O, Lerman A, Lerman LO. Role of renal cortical neovascularization in experimental hypercholesterolemia. Hypertension. 50: 729-736, 2007. Go to original source... Go to PubMed...
  7. Chait A, Brazg RL, Tribble DL, Krauss RM. Susceptibility of small, dense, low-density lipoproteins to oxidative modification in subjects with the atherogenic lipoprotein phenotype, pattern B. Am J Med. 94: 350-356, 1993. Go to original source... Go to PubMed...
  8. Chan PH. Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab. 21: 2-14, 2001. Go to original source... Go to PubMed...
  9. Davi G, Alessandrini P, Mezzetti A, Minotti G, Bucciarelli T, Costantini F, Cipollone F, Bon GB, Ciabattoni G, Patrono C. In vivo formation of 8-epi-prostaglandin F(2&alpha) is increased in hypercholesterolemia. Arterioscler Thromb Vasc Biol. 17: 3230-3235, 1997. Go to original source... Go to PubMed...
  10. Deyhim F, Lopez E, Gonzalez J, Garcia M, Patil BS. Citrus juice modulates antioxidant enzymes and lipid profiles in orchidectomized rats. J Med Food. 9: 422-426, 2006. Go to original source... Go to PubMed...
  11. Domagala B, Hartwich J, Szczeklik A. Incides of lipid peroxidation in patients with hypercholesterolemia and hypertriglyceridemia. Wien Klin Wochenschr. 101: 425-428, 1989.
  12. Eddy AA, Lui E, McCulloch L. Interstitial fibrosis in hypercholesterolemic rats: role of oxidation, matrix synthesis, and proteolytic cascades. Kidney Int. 53: 1182-1189, 1998. Go to original source... Go to PubMed...
  13. Evans PH. Free radicals in brain metabolism and pathology. Br Med Bull. 49: 577-587, 1993. Go to original source... Go to PubMed...
  14. Green CO, Wheatley AO, Osagie AU, Morrison E St. A, Asemota HN. Determination of polymethoxylated flavones in peels of selected Jamaican and Mexican citrus (Citrus spp.) cultivars by high-performance liquid chromatography. Biomed Chromatogr. 21: 48-54, 2007. Go to original source... Go to PubMed...
  15. Green CO Wheatley AO, McGrowder DA, Dilworth LL, Asemota HN. Hypolipidemic effects of Ortanique peel polymethoxylated flavones in rats with diet-induced hypercholesterolemia. J Food Biochem. 35: 1555-1560, 2011a. Go to original source...
  16. Green CO, Wheatley AO, Hanchard B, Gibson TN, McGrowder DA, Dilworth LL Asemota HN. Histopathological alterations in organ structures of hypercholesterolemic rats fed Ortanique peel polymethoxylated flavones. Basic Appl Pathol. 4: 71-77, 2011b. Go to original source...
  17. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 249: 7130-7139, 1974. Go to original source...
  18. Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine. 3rd edition. University Press, Oxford, 1999.
  19. Harborne J. Plant Flavonoids in Biology and Medicine. Alan R. Liss, New York 1993.
  20. Hexeberg S, Willumsen N, Rotevatn S, Hexeberg E, Berge RK. Cholesterol induced lipid accumulation in myocardial cells of rats. Cardiovasc Res. 27: 442-446, 1993. Go to original source... Go to PubMed...
  21. Ibrahim W, Lee US, Yeh CC, Szabo J, Bruckner G, Chow CK. Oxidative stress and antioxidant status in mouse liver: effects of dietary lipid, vitamin E and iron. J Nutr. 127: 1401-1406, 1997. Go to original source... Go to PubMed...
  22. Kannel WB, Castelli WP, Gordon T, McNamara PM. Serum cholesterol, lipoproteins, and the risk of coronary heart disease: The Framingham study. Ann Intern Med. 74: 1-12, 1971. Go to original source... Go to PubMed...
  23. Kim HJ, Oh GT, Park YB, Lee MK, Seo HJ, Choi MS. Naringin alters the cholesterol biosynthesis and antioxidant enzyme activities in LDL receptor-knockout mice under cholesterol fed condition. Life Sci. 74: 1621-1634, 2004. Go to original source... Go to PubMed...
  24. Kritharides L, Stocker R. The use of antioxidant supplements in coronary heart disease. Atherosclerosis. 164: 211-219, 2002. Go to original source... Go to PubMed...
  25. Lee YJ, Galoforo SS, Berns CM, Chen JC, Davis BH, Sim JE, Corry PM, Spitz DR. Glucose deprivation-induced cytotoxicity and alterations in mitogen-activated protein kinase activation are mediated by oxidative stress in multidrug-resistant human breast carcinoma cells. J Biol Chem. 273: 5294-5299, 1998. Go to original source... Go to PubMed...
  26. Lerman L, Textor SC. Pathophysiology of ischemic nephropathy: Urol Clin North Am. 28: 793-803, ix, 2001. Go to original source... Go to PubMed...
  27. Lledias F, Rangel P, Hansberg W. Oxidation of catalase by singlet oxygen. J Biol Chem. 273: 10630-10637, 1998. Go to original source... Go to PubMed...
  28. Mahfouz MM, Kummerow FA. Cholesterol-rich diets have different effects on lipid peroxidation, cholesterol oxides, and antioxidant enzymes in rats and rabbits. J Nutr Biochem. 11: 293-302, 2000. Go to original source... Go to PubMed...
  29. Manthey JA, Grohmann K. Phenols in citrus peel byproducts. Concentrations of hydroxycinnamates and polymethoxylated flavones in citrus peel molasses. J Agric Food Chem. 49: 3268-3273, 2001. Go to original source... Go to PubMed...
  30. Martens S, Mithofer A. Flavones and flavone synthases. Phytochemistry. 66: 2399-2407, 2005. Go to original source... Go to PubMed...
  31. Mataix J, Quiles JL, Huertas JR, Battino M, Manas M. Tissue specific interactions of exercise, dietary fatty acids, and vitamin E in lipid peroxidation. Free Radic Biol Med. 24: 511-521, 1998. Go to original source... Go to PubMed...
  32. McMurray JJ, Stewart S. Epidemiology, aetiology, and prognosis of heart failure. Heart. 83: 596-602, 2000. Go to original source... Go to PubMed...
  33. Melax H, Leeson TS. Comparative electron microscope studies of the myocardium in adult rats fed on normal and cholesterol diets. J Mol Cell Cardiol. 7: 195-202, 1975. Go to original source... Go to PubMed...
  34. Mendez GF, Cowie MR. The epidemiological features of heart failure in developing countries: a review of the literature. Int J Cardiol. 80: 213-219, 2001. Go to original source... Go to PubMed...
  35. Middleton E, Jr., Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev. 52: 673-751, 2000. Go to PubMed...
  36. Montilla P, Espejo I, Munoz MC, Bujalance I, Munoz-Castaneda JR, Tunez I. Effect of red wine on oxidative stress and hypercholesterolemia induced by feeding a high-cholesterol diet in rat. J Physiol Biochem. 60: 259-264, 2004. Go to original source... Go to PubMed...
  37. Moorhead JF, Chan MK, El-Nahas M, Varghese Z. Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease. Lancet. 2: 1309-1311, 1982. Go to original source... Go to PubMed...
  38. Napoli C, Postiglione A, Triggiani M, Corso G, Palumbo G, Carbone V, Ruocco A, Ambrosio G, Montefusco S, Malorni A, Condorelli M, Chiariello M. Oxidative structural modifications of low density lipoprotein in homozygous familial hypercholesterolemia. Atherosclerosis. 118: 259-273, 1995. Go to original source... Go to PubMed...
  39. Ohara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest. 91: 2546-2551, 1993. Go to original source... Go to PubMed...
  40. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 95: 351-358, 1979. Go to original source... Go to PubMed...
  41. Onody A, Csonka C, Giricz Z, Ferdinandy P. Hyperlipidemia induced by a cholesterol-rich diet leads to enhanced peroxynitrite formation in rat hearts. Cardiovasc Res. 58: 663-670, 2003. Go to original source... Go to PubMed...
  42. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 70: 158-169, 1967.
  43. Parmar HA, Kar A. Protective role of Citrus sinensis, Musa paradisiaca, and Punica granatum peels against diet-induced atherosclerosis and thyroid dysfunctions in rats. Nutr Res. 27: 710-718, 2007. Go to original source...
  44. Perlemuter G, Davit-Spraul A, Cosson C, Conti M, Bigorgne A, Paradis V, Corre MP, Prat L, Kuoch V, Basdevant A, Pelletier G, Oppert JM, Buffet C. Increase in liver antioxidant enzyme activities in non-alcoholic fatty liver disease. Liver Int. 25: 946-953, 2005. Go to original source... Go to PubMed...
  45. Pietta PG. Flavonoids as antioxidants. J Nat Prod. 63: 1035-1042, 2000. Go to original source... Go to PubMed...
  46. Prasad K Mantha SV, Kalra J, Lee P. Hypercholesterolemia-induced oxidative stress in heart and its prevention by vitamin E. Int J Angiology. 6: 13-17, 1997. Go to original source...
  47. Reiter RJ. Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J. 9: 526-533, 1995. Go to original source... Go to PubMed...
  48. Sanderson JE, Tse TF. Heart failure: a global disease requiring a global response. Heart. 89: 585-586, 2003. Go to original source... Go to PubMed...
  49. Schulze-Osthoff K, Bauer MK, Vogt M, Wesselborg S. Oxidative stress and signal transduction. Int J Vitam Nutr Res. 67: 336-342, 1997.
  50. Shohami E, Beit-Yannai E, Horowitz M, Kohen R. Oxidative stress in closed-head injury: brain antioxidant capacity as an indicator of functional outcome. J Cereb Blood Flow Metab. 17: 1007-1019, 1997. Go to original source... Go to PubMed...
  51. Sies H. Oxidative stress: oxidants and antioxidants. Exp Physiol. 82: 291-295, 1997. Go to original source... Go to PubMed...
  52. Sinet PM, Heikkila RE, Cohen G. Hydrogen peroxide production by rat brain in vivo. J Neurochem. 34: 1421-1428, 1980. Go to original source... Go to PubMed...
  53. Smith GD, Shipley MJ, Marmot MG, Rose G. Plasma cholesterol concentration and mortality. The Whitehall Study. JAMA. 267: 70-76, 1992. Go to original source... Go to PubMed...
  54. Stern K. On the absorbance of catalase. J Biol Chem. 121: 561-567, 1937. Go to original source...
  55. Stulak JM LA, Porcel MR, Caccitolo JA, Romero JC, Schaff HV, Napoli C, Lerman LO. Renal vascular function in hypercholesterolemia is preserved by chronic antioxidant supplementation. J Am Soc Nephrol. 12: 1882-1891, 2001. Go to original source...
  56. Sun J, Chen Y, Li M, Ge Z. Role of antioxidant enzymes on ionizing radiation resistance. Free Radic Biol Med. 24: 586-593, 1998. Go to original source... Go to PubMed...
  57. Sung MK Park MY. Effect of soybean saponins on the growth and antioxidant defense of human hepatocarcinoma cells. Third symposium on the role of the soy in preventing and treating chronic disease. 1999. Washington, DC., USA, October 31-November 3, 1999.
  58. Traystman RJ, Kirsch JR, Koehler RC. Oxygen radical mechanisms of brain injury following ischemia and reperfusion. J Appl Physiol. 71: 1185-1195, 1991. Go to original source... Go to PubMed...
  59. Vogt M, Bauer MK, Ferrari D, Schulze-Osthoff K. Oxidative stress and hypoxia/reoxygenation trigger CD95 (APO-1/Fas) ligand expression in microglial cells. FEBS Lett. 429: 67-72, 1998. Go to original source... Go to PubMed...
  60. Wassmann S, Wassmann K, Nickenig G. Modulation of oxidant and antioxidant enzyme expression and function in vascular cells. Hypertension. 44: 381-386, 2004. Go to original source... Go to PubMed...