Rutin improves the antioxidant status in streptozotocin-induced diabetic rat tissues

Article

Abstract

Rutin, a polyphenolic flavonoid, was investigated for its antioxidant potential in streptozotocin (STZ)-induced diabetic rats. Rats were rendered diabetic by a single intraperitoneal injection of streptozotocin (50 mg/kg). The levels of fasting plasma glucose and insulin were estimated. Lipid peroxidative products and antioxidants were estimated in liver, kidney and brain. Histopathological studies were carried out in these tissues. A significant (p < 0.05) increase in the levels of fasting plasma glucose, lipid peroxidative products (thiobarbituric acid reactive substances [TBARS] and lipid hydroperoxides [HP]) and a significant (p < 0.05) decrease in plasma insulin, enzymic antioxidants (superoxide dismutase [SOD], catalase, glutathione peroxidase [GPx] and glutathione reductase [GRx]) and nonenzymic antioxidants (reduced glutathione [GSH], vitamin C and E) in diabetic liver, kidney and brain were observed. Oral administration of rutin (100 mg/kg) for a period of 45 days significantly (p < 0.05) decreased fasting plasma glucose, increased insulin levels and improved the antioxidant status of diabetic rats by decreasing lipid peroxidative products and increasing enzymic and nonenzymic antioxidants. Normal rats treated with rutin (100 mg/kg) showed no significant (p < 0.05) effect on any of the parameters studied. Histopathological studies of the liver, kidney and brain showed the protective role of rutin. Thus, our study clearly shows that rutin has antioxidant effect in STZ-induced experimental diabetes.

Key words

rutin diabetes mellitus streptozotocin lipid peroxidation antioxidants 

References

  1. 1.
    World Health Organization/International Diabetes Federation: The Economics of Diabetes and Diabetes Care - A Report of the Diabetes Health Economics Study Group. WHO, Geneva, 1999Google Scholar
  2. 2.
    Craig WJ: Health-promoting properties of common herbs. Am J Clin Nutr 70: 491s–499s, 1999PubMedGoogle Scholar
  3. 3.
    Szkudelski T: The mechanism of alloxan and streptozotocin action in β-cells of the rat pancreas. Physiol Res 50: 536–546, 2001Google Scholar
  4. 4.
    Baynes JW: Role of oxidative stress in development of complications of diabetes mellitus. Diabetes 40: 405–412, 1991PubMedGoogle Scholar
  5. 5.
    Potter JD: Cancer prevention: epidemiology and experiment. Cancer Lett 114: 7–9, 1997PubMedCrossRefGoogle Scholar
  6. 6.
    Harborne JB: Plant phenolics. In: EA Bell and BV Charlwood (eds). Encyclopedia of plant physiology, Vol. 8. Secondary plant products. Springer Verlag, Berlin, 1986, pp. 329–395Google Scholar
  7. 7.
    Rice-Evans C, Packer L: In: Flavonoids in health and diseases, Marcel Decker Inc., New York, 1998, pp. 483–522Google Scholar
  8. 8.
    Middleton E, Kandaswami C, Theoharides TC: The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease and cancer. Pharmacol Rev 52: 673–751, 2000PubMedGoogle Scholar
  9. 9.
    Hollman PC, Katan MB: Absorption, metabolism and bioavailability of flavonoids. In: C Rice-Evans and L Packer (eds). Flavonoids in Health and Disease, Marcel Decker, New York, 1998, pp. 483–522Google Scholar
  10. 10.
    Havsteen B: Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol 32: 1141–1148, 1983PubMedCrossRefGoogle Scholar
  11. 11.
    Nakamura Y, Ishimitsu S, Tonogai Y: Effects of quercetin and rutin on serum and hepatic lipid concentrations, fecal steroid excretion and serum antioxidant properties. J Health Sci 46: 229–240, 2000Google Scholar
  12. 12.
    Hertog MG, Hollman PC, Katan MB, Kromhout D: Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands. Nutr Cancer 20: 21–29, 1993PubMedCrossRefGoogle Scholar
  13. 13.
    Erlund I, Kosonen T, Alfthan G, Perttunen KM, Kenraali J, Parantainen J, Aro J: Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers. Eur J Clin Pharmacol 56: 545–553, 2000PubMedCrossRefGoogle Scholar
  14. 14.
    Deschner EE, Ruperto J, Wong G, Newmark HL: Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia. Carcinogenesis 12: 1193–1196, 1991PubMedGoogle Scholar
  15. 15.
    Aleksandrov PN, Speranskaia TV, Bobkov Iu G, Zagorevskii VA, Zykov DA: Effect of rutin and esculamine on models of aseptic inflammation. Farmakol Toksikol 49: 84–86, 1986PubMedGoogle Scholar
  16. 16.
    Di Carlo G, Autore G, Izzo AA, Maiolino P, Mascolo N, Viola P, Diurno MV, Capasso F: Inhibition of intestinal motility and secretion by flavonoids in mice and rats: structure-activity relationships. J Pharm Pharmacol 45: 1054–1059, 1993PubMedGoogle Scholar
  17. 17.
    Bear WL, Teel RW: Effects of citrus flavonoids on the mutagenicity of heterocyclic amines and on cytochrome P450 1A2 activity. Anticancer Res 20: 3609–3614, 2000PubMedGoogle Scholar
  18. 18.
    Pozin VM, Skuratovskaia SG, Pocheptsova GA: Changes in the vascular wall and ischemic damages to the myocardium in reversible episodes of heart muscle ischemia. Fiziologicheskii Zhurnal 42: 10–16, 1996Google Scholar
  19. 19.
    Chen S, Gong J, Liu F, Mohammed U: Naturally occurring polyphenolic antioxidants modulate IgE-mediated mast cell activation. Immunology 100: 471–480, 2000PubMedCrossRefGoogle Scholar
  20. 20.
    Janbaz KH, Saeed SA, Gilani AH: Protective effect of rutin on paracetamol- and CCl4-induced hepatotoxicity in rodents. Fitoterapia 73: 557–563, 2002PubMedCrossRefGoogle Scholar
  21. 21.
    Gao Z, Xu H, Huang K: Effects of rutin supplementation on antioxidant status and iron, copper, and zinc contents in mouse liver and brain. Biol Trace Elem Res 88: 271–279, 2002PubMedCrossRefGoogle Scholar
  22. 22.
    Nagasawa T, Tabata N, Ito Y, Nishizawa N, Aiba Y, Kitts DD: Inhibition of glycation reaction in tissue protein incubations by water soluble rutin derivative. Mol Cell Biochem 249: 3–10, 2003PubMedCrossRefGoogle Scholar
  23. 23.
    Nagasawa T, Tabata N, Ito Y, Aiba Y, Nishizawa N, Kitts DD: Dietary G-rutin suppresses glycation in tissue proteins of streptozotocin-induced diabetic rats. Mol Cell Biochem 252: 141–147, 2003PubMedCrossRefGoogle Scholar
  24. 24.
    Kamalakkannan N, Stanely Mainzen Prince P: The antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocin-induced diabetic Wistar rats. Basic Clin Pharmacol Toxicol 98: 97–103, 2006PubMedCrossRefGoogle Scholar
  25. 25.
    Sridhar SB, Sheetal UD, Pai MRSM, Shastri MS: Preclinical evaluation of the antidiabetic effect of Eugenia jambolana seed powder in streptozotocin-diabetic rats. Brazilian J Med Biol Res 38: 462–468, 2005Google Scholar
  26. 26.
    Fraga CG, Leibovitz BE, Toppel AL: Lipid peroxidation measured as TBARS in tissue slices. Characterisation and comparison with homogenate and microsome. Free Radic Biol Med 4: 155–161, 1988PubMedCrossRefGoogle Scholar
  27. 27.
    Jiang ZY, Hunt JV, Wolff SP: Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low density lipoprotein. Ann Biochem 202: 384–387, 1992CrossRefGoogle Scholar
  28. 28.
    Ellman GL: Tissue sulfhydryl groups. Arch Biochem Biophys 82: 70–77, 1959PubMedCrossRefGoogle Scholar
  29. 29.
    Omaye ST, Turnbull TD, Sauberlich HE: Selected method for the determination of ascorbic acid in animal cells, tissues and fluids. In: D.B. McCormic and D.L. Wright (eds). Methods in Enzymology, Academic press, New York, 1979, pp. 3–11Google Scholar
  30. 30.
    Baker H, Frank O, Angelis B, Feingold S: Plasma tocopherol in man at various times after ingesting free or acetylated tocopherol. Nutr Rep Int 21: 531–536, 1951Google Scholar
  31. 31.
    Kakkar P, Das B, Viswanathan PN: A modified spectrophotometric assay of SOD. Indian J Biochem Biophys 21: 130–132, 1984PubMedGoogle Scholar
  32. 32.
    Sinha KA: Colorimetric assay of catalase. Ann Biochem 47: 389–394, 1972CrossRefGoogle Scholar
  33. 33.
    Rotruck JT, Pope AL, Ganther HE, Swanson AB: Selenium: Biochemical roles as a component of glutathione peroxidase. Science 179: 588–590, 1984CrossRefGoogle Scholar
  34. 34.
    Horn HD, Burns FH: Assay of glutathione reductase activity. In: HV Bergmeyer (ed). Methods of Enzymatic Analysis, Academic Press, New York, 1978, p. 142Google Scholar
  35. 35.
    Korkina LG, Afanas'ev IB: Antioxidant and chelating properties of flavonoids. Adv Pharmacol 38: 151–163, 1997PubMedCrossRefGoogle Scholar
  36. 36.
    Ferrali M, Signofrini C, Caciotti B, Sugherini L, Ciccoli D, Giachetti D, Comporti M: Protection against oxidative damage of erythrocyte membranes by the flavonoid quercetin and its relation to iron chelating activity. FEBS Letters 416: 123–139, 1997PubMedCrossRefGoogle Scholar
  37. 37.
    Elliott AJ, Scheiber SA, Thomas C, Pardini RS: Inhibition of glutathione reductase by flavonoids. Biochem Pharmacol 44: 1603–1608, 1992PubMedCrossRefGoogle Scholar
  38. 38.
    Kozlov AV, Ostrachovitch EA, Afanas'ev IB: Mechanism of inhibitory effects of chelating drugs on lipid peroxidation in rat brain homogenates. Biochem Pharmacol 47: 795–799, 1994PubMedCrossRefGoogle Scholar
  39. 39.
    Aliciguzel Y, Ozen I, Aslan M, Karayalcin U: Activities of xanthine oxidoreductase and antioxidant enzymes in different tissues of diabetic rats. J Lab Clin Med 142: 172–177, 2003PubMedCrossRefGoogle Scholar
  40. 40.
    Maritim AC, Sanders RA, Watkins III JB: Effects of α-lipoic acid on biomarkers of oxidative stress in streptozotocin-induced diabetic rats. J Nutr Biochem 14: 288–294, 2003PubMedCrossRefGoogle Scholar
  41. 41.
    Santini SA, Marra G, Giardina B, et al.: Defective antioxidant defenses and enhanced susceptibility to lipid peroxidation in uncomplicated IDDM. Diabetes 46: 1853–1858, 1997PubMedGoogle Scholar
  42. 42.
    Kamalakkannan N, Stanely Mainzen Prince P: Antidiabetic and antioxidant activity of Aegle marmelos extract in streptozotocin induced diabetic rats. Pharm Biol 42: 125–130, 2004CrossRefGoogle Scholar
  43. 43.
    Yadav P, Sarkar S, Bhatnagar D: Action of Capparis deciduas against alloxan-induced oxidative stress and diabetes in rat tissues. Pharmacol Res 36: 221–228, 1997PubMedCrossRefGoogle Scholar
  44. 44.
    Gumieniczek A: Effects of repaglinide on oxidative stress in tissues of diabetic rabbits. Diab Res Clin Pract 68: 89–95, 2005CrossRefGoogle Scholar
  45. 45.
    Sen CK: Nutritional biochemistry of cellular glutathione. J Nutr Biochem 8: 660–672, 1997CrossRefGoogle Scholar
  46. 46.
    Dominguez C, Ruiz E, Gussinye M, Carrascosa A: Oxidative stress at onset and in early stages of type I diabetes in children and adolescents. Diab Care 21: 1736–1742, 1998Google Scholar
  47. 47.
    Fang YZ, Yang S, Wu G: Free radicals, antioxidants and nutrition. Nutrition 18: 872–879, 2002PubMedCrossRefGoogle Scholar
  48. 48.
    Evelson P, Susemihl C, Villarreal I, Llesuy S, Rodriguez R, Peredo H, Lemberg A, Perazzo J, Filinger E: Hepatic morphological changes and oxidative stress in chronic streptozotocin-diabetic rats. Ann Hepatol 4: 115–120, 2005PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Department of Biochemistry and BiotechnologyAnnamalai UniversityAnnamalainagarIndia

Personalised recommendations