Molecular and Cellular Biochemistry

, Volume 275, Issue 1–2, pp 85–94 | Cite as

Garlic supplementation prevents oxidative DNA damage in essential hypertension

Article

Abstract

Oxygen-free radicals and other oxygen/nitrogen species are constantly generated in the human body. Most are intercepted by antioxidant defences and perform useful metabolic roles, whereas others escape to damage biomolecules like DNA, lipids and proteins. Garlic has been shown to contain antioxidant phytochemicals that prevent oxidative damage. These include unique water-soluble organosulphur compounds, lipid-soluble organosulphur compounds and flavonoids. Therefore, in the present study, we have tried to explore the antioxidant effect of garlic supplementation on oxidative stress-induced DNA damage, nitric oxide (NO) and superoxide generation and on the total antioxidant status (TAS) in patients of essential hypertension (EH). Twenty patients of EH as diagnosed by JNC VI criteria (Group I) and 20 age and sex-matched normotensive controls (Group II) were enrolled in the study. Both groups were given garlic pearls (GP) in a dose of 250 mg per day for 2 months. Baseline samples were taken at the start of the study, i.e. 0 day, and thereafter 2 months follow-up. 8-Hydroxy-2′-deoxyguanosine (8-OHdG), lipids, lipid peroxidation (MDA), NO and antioxidant vitamins A, E and C were determined. A moderate decline in blood pressure (BP) and a significant reduction in 8-OHdG, NO levels and lipid peroxidation were observed in Group I subjects with GP supplementation. Further, a significant increase in vitamin levels and TAS was also observed in this group as compared to the control subjects. These findings point out the beneficial effects of garlic supplementation in reducing blood pressure and counteracting oxidative stress, and thereby, offering cardioprotection in essential hypertensives.

Keywords

essential hypertension garlic 8-hydroxy-deoxy-2′guanosine oxidative stress oxygen-free radicals 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Dates JA: Antihypertensive agents and the drug therapy of hypertension. In: P.B. Molinoff, R.V. Ruddom (eds). Goodman Gilman’s. The Pharmacological Basis of Therapeutics, 9th edn., Mc-Graw Hill, New~York, 1996, pp 780–800Google Scholar
  2. 2.
    Williams GH: Hypertensive vascular diseases. In: K. Isselbacher, E. Braunwald, J.D. Wilson et~al. (eds). Harrison’s Principles of Internal Medicine, 14th edn., McGraw-Hills, New York, 1967, pp 1380–1394Google Scholar
  3. 3.
    Leuritzen CL: Hypertension and pregnancy. In: J. Rosenthal (ed). Arterial Hypertension, Pathogenesis, Diagnosis and Therapy, Springer Verlag, New York, 1982, pp 102–116Google Scholar
  4. 4.
    Raptis S: Hypertension and diabetes mellitus. In: J. Rosenthal (ed). Arterial Hypertension, Pathogenesis, Diagnosis and Therapy, Springer Verlag, New York, 1982, pp 93–100Google Scholar
  5. 5.
    Weschsler J, Bitschunert H: Hypertension and obesity. In: J. Rosenthal (ed). Arterial Hypertension Pathogenesis, Diagnosis and Therapy. Springer Verlag, New York, 1982, pp 62–78Google Scholar
  6. 6.
    Helmut S: Oxidative stress: from basic research to clinical applications. Am J Med 30: 3031S–3037S, 1991Google Scholar
  7. 7.
    Dhalla NS, Temsah RM, Natticaden T: Role of oxidative stress in cardiovascular diseases. J Hypertens 18: 655–673, 2000Google Scholar
  8. 8.
    Halliwell B: Oxidants and human diseases: Some new concepts. FASEB 5: 358–364, 1987Google Scholar
  9. 9.
    Ames BN, Shigenaga MK, Hagen TM: Oxidants, antioxidants and the degenerative diseases of ageing. PNAS 90: 7915–7922, 1993Google Scholar
  10. 10.
    Tagami M, Yamagata K, Fujino H, Nara Y, Nakagawa K, Kubota A, Numano F, Yamori Y: Genetic vulnerability of cortical neurons isolated from stroke-prone spontaneously hypertensive rats in hypoxia and oxygen reperfusion. Hypertens Res 22: 23–29, 1999Google Scholar
  11. 11.
    Lacy F, O’Connor D, Schmid-Schenbein G: Plasma hydrogen peroxide production in hypertensives and normotensive subjects at genetic risk of hypertension. J Hypertens 16: 291–303, 1998Google Scholar
  12. 12.
    Russo C, Olivieri O, Girelli D, Faccini G, Zennari LM, Lombardi S, Corrocher R: Antioxidant status and lipid peroxidation in patients with essential hypertension. J Hypertens 16: 1267–1271, 1998Google Scholar
  13. 13.
    Dample B, Harrison L: Repair of oxidative damage to DNA: Enzymology and biology. Ann Rev Biochem 63: 915–924, 1994Google Scholar
  14. 14.
    Halliwell B: Can oxidative DNA damage be used as a biomarker of cancer risk in humans? Free Radic Res 22: 23–29, 1998Google Scholar
  15. 15.
    Birmhom HK: The production of DNA strand breaks in human leukocytes by superoxide anion. Proc Natl Acad Sci USA 82: 80–88, 1985Google Scholar
  16. 16.
    Kasai H: Analysis of a form of oxidative DNA damage, 8-hydroxy-2′ deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutat Res 387: 146–163, 1997Google Scholar
  17. 17.
    Totter HR: Spontaneous cancer and its possible relationship to oxygen metabolism. Proc Natl Acad Sci USA 77: 1763–1767, 1980Google Scholar
  18. 18.
    Burdon RH, Allingana D, Gill V: Endogenously generated active oxygen species and cellular glutathione levels in relation to BHK-21 cell proliferation. Free Radic Res 21: 121–134, 1994Google Scholar
  19. 19.
    Feig DI, Loeb LA: Mechanisms of mutation by oxidative DNA damage, reduced fidelity of mammalian DNA polymerase. J Biochem 32: 4466–4473, 1993Google Scholar
  20. 20.
    Chaudhary AK, Nokubo M, Reddy GR, et~al.: Detection of endogenous malondialdehyde deoxy-guanosine adducts in human liver. Science 265: 1580–1582, 1994Google Scholar
  21. 21.
    EL Ghissassi F, Barbin A, Nair J, Bartsch H: Formation of 1N6-ethenoadenine and 3,N4-ethenocytosine by lipid peroxidation products and nucleic acid bases. Chem Res Toxicol 8: 278–283, 1995Google Scholar
  22. 22.
    Simic MG: Urinary biomarkers and the rate of DNA damage in carcinogenesis. Mutat Res 267: 277–290, 1992Google Scholar
  23. 23.
    Loft S, Vistisen K, Ewertz MT, Jonneland A, Overad K, Poulsen E: Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretions in humans. Influence of smoking, gender and body mass index. Carcinogenesis 13: 2241–2247, 1992Google Scholar
  24. 24.
    Loft S, Deng XS, Tuo J: Experimental study of oxidative DNA damage. Free Radic Res 29: 525–539, 1993Google Scholar
  25. 25.
    Mo Jim Maki H, Sakiguchi M: Hydrolytic elimination of a mutagenic nucleotide 8-oxod GTP by human 18-KDa protein: sensitisation of nucleotide pool. Proc Soc Natl Acad Sci USA 89: 11021–11025, 1992Google Scholar
  26. 26.
    Shigenaga M, Gimeno C, Ames B: Urinary 8-hydroxy 2′-deoxyguano- sine as a biological marker of in vivo oxidative DNA damage. Proc Soc Natl Acad Sci USA 86: 9697–9701, 1989Google Scholar
  27. 27.
    Yeh Y-Y, Lijuan L: Cholesterol lowering effects of garlic extracts an organosulfur compounds: human and animal studies. J Nutr 131: 989S–993S, 2001Google Scholar
  28. 28.
    Koscielny J, Klussendorf D, Schmidt R, Radtke H, Siegel G, Kiesewetter H: Study of garlic extracts and fractions on cholesterol plasma levels and vascular reactivity in cholesterol-fed rats. J Nutr 131: 994S–999S, 2001Google Scholar
  29. 29.
    Spigelski D, Jones Peter JH: Efficacy of garlic supplementation in lowering serum cholesterol levels. Nutr Rev 59: 236–241, 2001Google Scholar
  30. 30.
    Foushee DB, Ruffin J, Banerjee U: Garlic as a natural agent for the treatment of hypertension: A preliminary report. Cytobios 34: 145–152, 1982Google Scholar
  31. 31.
    Steiner M, Li W: Aged garlic as a modulator of cardiovascular risk factors: Adose finding study on the effects of AGE on platelet function. J Nutr 131: 980S–984S, 2001Google Scholar
  32. 32.
    Bordia A, Verma SK, Srivastava KC: Effect of garlic (Allium sativum) on blood lipids, blood sugar, fibrinogen and fibrinolytic activity in patients of coronary heart disease. Prostaglandins. Leuk Essential Fatty acids 58: 257, 1998Google Scholar
  33. 33.
    Prasad K, Lax dal VA, Yu M, Rancy BL: Antioxidant activity of allicin, an active principle in garlic. Mol Cell Biochem 148: 183, 1995Google Scholar
  34. 34.
    The Sixth Report of Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure. Arch Intern Med 157: 2401–2445, 1997Google Scholar
  35. 35.
    Green LC, Wagner DA, Glagowski J, Skipper PL, Wishnak JS, Tannenbaum SR: Analysis of nitrate, nitrite and [15N] nitrate in biological fluids. Anal Biochem 126: 131–138, 1982Google Scholar
  36. 36.
    Boyde TRC, Rahmatullah M: Optimisation of conditions for colorimetric determination of citrulline using diacetyl monoxime. Anal Biochem 107: 424–431, 1980Google Scholar
  37. 37.
    Thurnham DI, Smith E, Flora SP: Concurrent liquid chromatographic assay of retinol, α-tocopherol, carotene, cryptoxanthin in plasma with tocopherol acetate as internal standard. Clin Chem 34: 377–381, 1988Google Scholar
  38. 38.
    Margolis SA, Paule RC, Ziegler RG: Ascorbic and dehydroascorbic acids measured in plasma preserved with dithiothreitol or metaphosphoric acid. Clin Chem 36: 1750–1755, 1990Google Scholar
  39. 39.
    Benzie FF, Strain JJ: Ferric reducing/antioxidant power assay: Direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Anal Biochem 239: 15–27, 1996Google Scholar
  40. 40.
    Boyum A: Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Invest 21: 77–89, 1968Google Scholar
  41. 41.
    Cheung K, Archibald AC, Robinson MF: Luminol-dependent chemiluminescence produced by PMNL’s stimulated by immune complex. Aust J Exp Biol Med Sci 62: 403–419, 1984Google Scholar
  42. 42.
    Clerc M, Peuchant E, Carbonneau MA, Sess D: Free and bound malondialdehyde measured as thiobarbituric acid adduct by HPLC in serum and plasma. Clin Chem 37: 1423–1429, 1991Google Scholar
  43. 43.
    Lahiri DK, Bye S, Nurnber JL, Hodes ME, Crisp M: A non-organic and non-enzymatic extraction method gives higher yield of genomic DNA from whole blood sample than do other methods tested. J Biochem Biophys Methods 25: 193–205, 1992Google Scholar
  44. 44.
    Maniatis T, Sambrook J, Fritch EF: Molecular Cloning: A Laboratory Manual, 2nd edn., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989, pp 6.3–6.4Google Scholar
  45. 45.
    Whetton PK: Epidemiology of hypertension. Lancet 344: 101–106, 1994Google Scholar
  46. 46.
    Silaqy CA, Neil HAW: A meta analysis of the effect of garlic on blood pressure. J Hypertens 12: 463–468, 1994Google Scholar
  47. 47.
    Siegel G, Nuck R, Schnalke F, Michel F: Molecular evidences for phytopharmacological K channel opening by garlic in human vascular smooth muscle cell membranes. Phytother Res 12: S149–S151, 1998Google Scholar
  48. 48.
    Suetsuna K: Isolation and characterization of angiotensin 1 converting enzyme inhibitor peptides derived from Allium sativum L (garlic). J Nutr Biochem 9: 415–419, 1998Google Scholar
  49. 49.
    Pedraza-Chaverri J, Tapia E, Medina Campus ON: Garlic prevents hypertension by chronic inhibition of nitric oxide synthesis. Life Sci 62: 71–72, 1998Google Scholar
  50. 50.
    Mc Intyre M, Hamilton CA, Rees DD, Reid JL, Dominiczac AF: Sex differences in the abundance of endothelial nitric oxide in a model of hypertension. Hypertension 30: 1517–1524, 1997Google Scholar
  51. 51.
    Vaziri ND, Ni Z, Ovesi F: Upregulation of renal and vascular nitric oxide synthase in young spontaneously hypertensive rats. Hypertension 31: 1248–1254, 1998Google Scholar
  52. 52.
    Luscher TF: Imbalance between endothelium-derived relaxing and contracting factors: A new concept in hypertension. Am J Hypertens 4: 317–330, 1990Google Scholar
  53. 53.
    Gryglewski RJ, Palmer RMJ, Moncada S: Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 320: 454–456, 1986Google Scholar
  54. 54.
    Salahudeen AK: Role of lipid peroxidation in H2O2-induced renal epithelial (LLK-PK) cell injury. Am J Physiol 268: F30–F38, 1995Google Scholar
  55. 55.
    Takabashi K, Nammour TRM, Fukunaga M, Ebert J, Murrow JD, Hoover RL, Badr K: Glomerular action of a free radical-generated novel prostaglandin, 8-epi prostaglandin, 8-epi-PGF2α in the rat: Evidence for interaction with thromboxane A2 receptors. J Clin Invest 90: 136–141, 1992Google Scholar
  56. 56.
    Lin PJ, Pearson PJ, Cartier R, Schaff HV: Superoxide anion mediates the endothelium-dependent contraction to serotonin by regenerated endothelium. Thorac Cardiovasc Surg 102: 378–385, 1991Google Scholar
  57. 57.
    Tesfamariam B, Cohen RA: Role of Superoxide anion and endothelium in vasoconstrictor action of prostaglandin endoperoxide. Am J Physiol 262: H1915–H1919, 1992Google Scholar
  58. 58.
    Vaziri ND, Wang XQ: cGMP-mediated negative feedback regulation of endothelial nitric oxide synthase expression by nitric oxide. Hypertension 34: 1237–1241, 1999Google Scholar
  59. 59.
    Attri J, Dhawan V, Mahmood S, Pandhi P, Parwana HK, Nath R: Effect of vitamin C supplementation on oxidative DNA damage in an experimental model of lead-induced hypertension. Ann Nutr Metab 47: 294–301, 2003Google Scholar
  60. 60.
    Negishi H, Njelekela M, Ikeda K, Sagara M, Noguchi T, Kuga S: Assessment of in vivo oxidative stress in hypertensive rats and hypertensive subjects in Tanzania, Africa. Hypertens Res 23: 285–289, 2000Google Scholar
  61. 61.
    Inoue S, Kawanishi S: Oxidative DNA damage induced by simultaneous generation of nitric oxide and superoxide. FEBS Lett 371: 86–88, 1995Google Scholar
  62. 62.
    Kumar KU, Das UN: Are free radicals involved in the pathophysiology of human essential hypertension? Free Radic Res Commun 19: 59–66, 1993Google Scholar
  63. 63.
    Singal PK, Khaper N, Palace U, Kumar D: The role of oxidative stress in the genesis of heart disease. Cardiovasc Res 40: 426–432, 1998Google Scholar
  64. 64.
    Dhawan V, Jain S: Effect of garlic supplementation on oxidized low-density lipoproteins and lipid peroxidation in patients of essential hypertension. Mol Cell Biochem 166: 115–119, 2000Google Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Department of Experimental Medicine and BiotechnologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
  2. 2.Department of Internal MedicinePostgraduate Institute of Medical Education and ResearchChandigarhIndia
  3. 3.Department of Experimental Medicine and BiotechnologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia

Personalised recommendations