Full-text resources of PSJD and other databases are now available in the new Library of Science.
Visit https://bibliotekanauki.pl

PL EN


Preferences help
enabled [disable] Abstract
Number of results

Journal

2010 | 5 | 5 | 620-626

Article title

Hyperhomocysteinemia’s effect on antioxidant capacity in rats

Content

Title variants

Languages of publication

EN

Abstracts

EN
Hyperhomocysteinemia represents elevated homocysteine (Hcys) concentrations in blood above the normal range. In humans, the normal range of homocysteine is 5.0–15.9 mM/ml. High levels of homocysteine disturb the normal epithelial functions and correlate with cardiovascular diseases even at slightly increased concentrations. In homocysteine metabolism, vitamins play an important role. The mechanism through which homocysteine triggers these effects is not yet elucidated, but the involvement of reactive species may be the answer. It is not known whether the intra- or extracellular antioxidant system is more affected by elevated homocysteine levels. We studied the effects of hyperhomocysteinemia on the intra- and extracellular antioxidant defense systems in two different types of diet in rats. Type I was food with low folic acid and vitamin B12 content and type II was food with normal amounts of these two vitamins. Hyperhomocysteinemia was experimentally induced by oral administration of methionine 2 mg/kg body weight, single daily dose, for a 15-day period. Plasma concentrations of homocysteine were measured using an HPLC method. In the response of the intracellular antioxidant defense system against hyperhomocysteinemia, we determined the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in red blood cells, using RANDOX kits for manual use. For the extracellular response we determined the plasma total antioxidant status (TAS) also using a RANDOX kit for manual use. Our data show that methionine load induces hyperhomocysteinemia despite normal vitamin supply in rats. SOD activity rose with simultaneous decrease in GPx activity independently of diet; this might suggest that the intracellular defense system was disturbed by the rise in homocysteine level. TAS decrease suggests that the extracellular antioxidant defense was also affected. We assume that hyperhomocysteinemia is directly linked to reactive species generation and the intracellular space seems to be more affected than the extracellular one.

Keywords

EN

Publisher

Journal

Year

Volume

5

Issue

5

Pages

620-626

Physical description

Dates

published
1 - 10 - 2010
online
20 - 8 - 2010

Contributors

  • Department of Biochemistry, Univ. Med. Pharm. “Gr. T. Popa”, 700115, Iasi, Romania
author
  • Department of Pharmacology and Algesiology, Univ. Med. Pharm. “Gr. T. Popa”, 700115, Iasi, Romania
  • Department of Biochemistry, Univ. Med. Pharm. “Gr. T. Popa”, 700115, Iasi, Romania
author
  • Department of Pharmacology and Algesiology, Univ. Med. Pharm. “Gr. T. Popa”, 700115, Iasi, Romania
  • Laboratory of Inorganic Polymers, Inst. of Macromol. Chem. “P. Poni”, 700523, Iasi, Romania
  • Department of Biochemistry, Univ. Med. Pharm. “Gr. T. Popa”, 700115, Iasi, Romania
  • Department of Biochemistry, Univ. Med. Pharm. “Gr. T. Popa”, 700115, Iasi, Romania
author
  • Department of Pharmacology and Algesiology, Univ. Med. Pharm. “Gr. T. Popa”, 700115, Iasi, Romania

References

  • [1] McCully K, Wilson R. Homocysteine theory of arteriosclerosis, Atherosclerosis, 1975, 22, 215–227 http://dx.doi.org/10.1016/0021-9150(75)90004-0[Crossref]
  • [2] Starkekbaum G, Harlan J. Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine, J Clin Invest, 1986, 77, 1370–1376 http://dx.doi.org/10.1172/JCI112442[Crossref]
  • [3] Stamler J, Loscallzo J. Endothelium-derived relaxing factor modulates the atherothrombogenic effects of homocysteine, J Cardiol Pharmacol, 1992, 20, S202–S204 [Crossref]
  • [4] Stamler J, Osborne J, Jaraki O. et al. Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen, J Clin Invest, 1993, 91, 308–318. http://dx.doi.org/10.1172/JCI116187[Crossref]
  • [5] Upchurch GJ, Welch G, Loscalzo J. Homocysteine EDRF and endothelial function. J Nutr, 1996, 126, 1290S–1294S
  • [6] Upchurch GJ, Welch G, Fabian A. et al. Homocyst(e) ine decreases bioavailable nitric oxide by a mechanism involving glutathione peroxidase, J Biol Chem, 1997, 272, 17012–17017 http://dx.doi.org/10.1074/jbc.272.27.17012[Crossref]
  • [7] Kanani PM, Sinkey CA, Browning RL. et al. Role of oxidant stress in endothelial dysfunction produced by experimental hyperhomocyst(e)inemia in humans, Circulation, 1999, 100, 1161–1168 [PubMed][Crossref]
  • [8] Topol G, Brunet A, Millanvoye E. et al. Homocysteine induces oxidative stress by uncoupling of NO synthase through reduction of tetrahydrobiopterin, Free Radic Biol Med, 2004, 36, 1532–1541 http://dx.doi.org/10.1016/j.freeradbiomed.2004.03.019[Crossref]
  • [9] Al-Daghri NM, Al-Attas OS. Homocysteinemia, hypertension, and family history of diabetes in a smoking male population in Saudi Arabia, Central European Journal of Medicine, 2008, 3(2), 167–172 http://dx.doi.org/10.2478/s11536-008-0019-9[WoS][Crossref]
  • [10] Wotherspoon F, Laight DW, Shaw KM, Cummings MH. Review: Homocysteine, endothelial dysfunction and oxidative stress in type 1 diabetes mellitus, The British Journal of Diabetes & Vascular Disease, 2003, 3(5), 334–340 http://dx.doi.org/10.1177/14746514030030050401[Crossref]
  • [11] Wu L, Wu J, Hunt S. et al. Plasma homocyst(e) ine as a risk factor for early familial coronary artery disease, Clin Chem, 1994, 40, 552–561 [PubMed]
  • [12] Dalery K, Lussier-Cacan S, Selhub J. et al. Homocysteine and coronary artery disease in French Canadian subjects: relation with vitamins B12, B6, pyridoxal phosphate, and folate, Am J Cardiol, 1995, 75, 1107–1111 http://dx.doi.org/10.1016/S0002-9149(99)80739-5[Crossref]
  • [13] Verhoef P, Stampfer M, Buring J. et al. Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12 and folate, Am J Epidemiol, 1996, 14, 845–859 [Crossref]
  • [14] Verhoef P, Kok F, Kruyssen D. et al. Plasma total homocysteine, B vitamins, and risk of coronary atherosclerosis, Arterioscler Thromb Vasc Biol, 1997, 17, 989–995 [PubMed][Crossref]
  • [15] Robinson K, Arheart K, Refsum H. et al. for the European COMAC Group. Low circulating folate and vitamin B6 concentrations. Risk factors for stroke, peripheral vascular disease, and coronary artery disease, Circulation 1998, 97, 437–443 [Crossref]
  • [16] McCully K, Ragsdale B. Production of arteriosclerosis by homocysteinemia, Am J Pathol 1970, 61, 1–8 [PubMed]
  • [17] Harker L, Harian J, Ross R. Effect of sulfinpyrazone on homocysteine-induced endothelial injury and arteriosclerosis in baboons, Circ Res, 1983, 53, 731–739 [Crossref][PubMed]
  • [18] Weiss N. Mechanisms of increased vascular oxidant stress in hyperhomocysteinemia and its impact on endothelial function, Curr Drug Metab, 2005, 6, 27–36 http://dx.doi.org/10.2174/1389200052997357[Crossref]
  • [19] Schafer FQ, Buettner GR, Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple, Free Radic. Biol. Med., 2001, 30(11), 1191–212 http://dx.doi.org/10.1016/S0891-5849(01)00480-4[Crossref]
  • [20] Lennon SV, Martin SJ, Cotter TG. Dose-dependent induction of apoptosis in human tumour cell lines by widely diverging stimuli. Cell Prolif, 1991, 24(2), 203–14 http://dx.doi.org/10.1111/j.1365-2184.1991.tb01150.x[Crossref]
  • [21] Boyce N. Oxidative Stress Testing: A New Addition to Lab Menus?, Clin. Lab News, 1997, 23, 1–2
  • [22] Bald E, Kaniowska E, Chwatko G, Glowacki R. Liquid chromatographic assessment of total and protein-bound homocysteine in human plasma, Talanta, 2000, 50, 1233–1243 http://dx.doi.org/10.1016/S0039-9140(99)00235-0[Crossref]
  • [23] Chwatko G, Bald G. Determination of different species of homocysteine in human plasma by highperformance liquid chromatography with ultraviolet detection, Journal of Chromatography A, 2002, 949(1–2), 141–151 http://dx.doi.org/10.1016/S0021-9673(01)01343-7[Crossref]
  • [24] Khandanpour N, Loke YK, Meyer FJ, Jennings B, Armon MP, Homocysteine and peripheral arterial disease: systematic review and meta-analysis, Eur J Vasc Endovasc Surg., 2009, 38(3), 316–22 http://dx.doi.org/10.1016/j.ejvs.2009.05.007[WoS][Crossref]
  • [25] Hirche F, Schröder A, Knoth B, Stangl GI, Eder K. Methionine-induced elevation of plasma homocysteine concentration is associated with an increase of plasma cholesterol in adult rats, Ann Nutr Metab, 2006, 50, 139–146 http://dx.doi.org/10.1159/000090635[Crossref]
  • [26] Herbert V, Zalusky R. lnterrelation of vitamin B12 and folic metabolism: folic acid clearance studies, J Clin Invest, 1962, 41, 1263–1276 http://dx.doi.org/10.1172/JCI104589[Crossref]
  • [27] Selhub J. Homocysteine metabolism, Annu Rev Nutr, 1999, 19, 217–246 http://dx.doi.org/10.1146/annurev.nutr.19.1.217[Crossref]
  • [28] Ueland PM, Refsum H, Male R, Lillehaug JR. Disposition of endogenous homocysteine by mouse fibroblast C3H/10T1/2 CI 8 and the chemically transformed C3H/10T1/2 MCA CI 16 cells following methotrexate exposure, J Natl Cancer Inst, 1986, 77, 283–289
  • [29] Christensen B, Refsum H, Vintermyr O, Ueland PM. Homocysteine export from cells cultured in the presence of physiological or superfluous levels of methionine: methionine loading of nontransformed, transformed, proliferating, and quiescent cells in culture, J Cell Biol, 1999,146, 52–62

Document Type

Publication order reference

Identifiers

YADDA identifier

bwmeta1.element.-psjd-doi-10_2478_s11536-010-0032-7
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.