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Erschienen in: Cardiovascular Toxicology 1/2011

01.03.2011

Homocysteine Induces Oxidative–Nitrative Stress in Heart of Rats: Prevention by Folic Acid

verfasst von: Janaína Kolling, Emilene B. Scherer, Aline Andrea da Cunha, Maira Jaqueline da Cunha, Angela T. S. Wyse

Erschienen in: Cardiovascular Toxicology | Ausgabe 1/2011

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Abstract

Hyperhomocysteinemia is a risk factor for cardiovascular disease, stroke, and thrombosis; however, the mechanisms by which homocysteine triggers these dysfunctions are not fully understood. In the present study, we investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative stress, namely thiobarbituric acid reactive substances, an index of lipid peroxidation, 2′,7′-dichlorofluorescein (H2DCF) oxidation, activities of antioxidant enzymes named superoxide dismutase and catalase, as well as nitrite levels in heart of young rats. We also evaluated the effect of folic acid on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injection of homocysteine (0.3–0.6 μmol/g body weight) and/or folic acid (0.011 μmol/g body weight) from their 6th to the 28th day of life. Controls and treated rats were killed 1 h and/or 12 h after the last injection. Results showed that chronic homocysteine administration increases lipid peroxidation and reactive species production and decreases enzymatic antioxidant defenses and nitrite levels in the heart of young rats killed 1 h, but not 12 h after the last injection of homocysteine. Folic acid concurrent administration prevented homocysteine effects probable by its antioxidant properties. Our data indicate that oxidative stress is elicited by chronic hyperhomocystenemia, a mechanism that may contribute, at least in part, to the cardiovascular alterations characteristic of hyperhomocysteinemic patients. If confirmed in human beings, our results could propose that the supplementation of folic acid can be used as an adjuvant therapy in cardiovascular alterations caused by homocysteine.
Literatur
1.
Zurück zum Zitat Herrmann, W., Quast, S., Ullrich, M., Schultze, H., Bodis, M., & Geisel, J. (1999). Hyperhomocysteinemia in high-aged subjects: Relation of B-vitamins, folic acid, renal function and the methylenetetrahydrofolate reductase mutation. Atherosclerosis, 144, 91–101.CrossRefPubMed Herrmann, W., Quast, S., Ullrich, M., Schultze, H., Bodis, M., & Geisel, J. (1999). Hyperhomocysteinemia in high-aged subjects: Relation of B-vitamins, folic acid, renal function and the methylenetetrahydrofolate reductase mutation. Atherosclerosis, 144, 91–101.CrossRefPubMed
2.
Zurück zum Zitat Hansrani, M., Gillespie, J. I., & Stansby, G. (2002). Homocysteine in Myointimal Hyperplasia. European Journal of Vascular and Endovascular Surgery, 23, 3–10.CrossRefPubMed Hansrani, M., Gillespie, J. I., & Stansby, G. (2002). Homocysteine in Myointimal Hyperplasia. European Journal of Vascular and Endovascular Surgery, 23, 3–10.CrossRefPubMed
3.
Zurück zum Zitat Mudd, S. H., Levy, H. L., & Skovby, F. (2001). Disorders of transsulfuration. In C. R. Scriver, A. L. Beaudet, W. S. Sly, & D. Valle (Eds.), The metabolic and molecular basis of inherited disease (Vol. 2, pp. 1279–1327). New York: McGraw-Hill. Mudd, S. H., Levy, H. L., & Skovby, F. (2001). Disorders of transsulfuration. In C. R. Scriver, A. L. Beaudet, W. S. Sly, & D. Valle (Eds.), The metabolic and molecular basis of inherited disease (Vol. 2, pp. 1279–1327). New York: McGraw-Hill.
4.
Zurück zum Zitat Fowler, B. (1997). Disorders of homocysteine metabolism. Journal of Inherited Metabolic Disease, 20, 270–285.CrossRefPubMed Fowler, B. (1997). Disorders of homocysteine metabolism. Journal of Inherited Metabolic Disease, 20, 270–285.CrossRefPubMed
5.
Zurück zum Zitat De Franchis, R., Sperandeo, M. P., Sebastio, G., & Andria, G. (1998). Clinical aspects of cystathionine β-synthase: How wide is the spectrum? European Journal of Pediatrics, 157, 67–70.CrossRef De Franchis, R., Sperandeo, M. P., Sebastio, G., & Andria, G. (1998). Clinical aspects of cystathionine β-synthase: How wide is the spectrum? European Journal of Pediatrics, 157, 67–70.CrossRef
6.
Zurück zum Zitat Kuhn, W., Roebroek, R., Blom, H., van Oppenraaij, D., Przuntek, H., Kretschmer, A., et al. (1998). Elevated plasma levels of homocysteine in Parkinson’s disease. European Neurology, 40, 225–227.CrossRefPubMed Kuhn, W., Roebroek, R., Blom, H., van Oppenraaij, D., Przuntek, H., Kretschmer, A., et al. (1998). Elevated plasma levels of homocysteine in Parkinson’s disease. European Neurology, 40, 225–227.CrossRefPubMed
7.
Zurück zum Zitat Harker, L. A., Harlan, J. M., & Ross, R. (1983). Effect of sulfinpyrazone on homocysteine-induced endothelial injury and arteriosclerosis in baboons. Circulation Research, 53, 731–739.PubMed Harker, L. A., Harlan, J. M., & Ross, R. (1983). Effect of sulfinpyrazone on homocysteine-induced endothelial injury and arteriosclerosis in baboons. Circulation Research, 53, 731–739.PubMed
8.
Zurück zum Zitat Halliwell, B., & Gutteridge, J. M. (1984). Oxigen toxicity, oxygen radicals, transition metals and disease. Biochemical Journal, 219, 1–14.PubMed Halliwell, B., & Gutteridge, J. M. (1984). Oxigen toxicity, oxygen radicals, transition metals and disease. Biochemical Journal, 219, 1–14.PubMed
9.
Zurück zum Zitat White, A. R., Huang, X., Jobling, M. F., Barrow, C. J., Beyreuther, K., Masters, C. L., et al. (2001). Homocysteine potentiates copper- and amyloid beta peptide-mediated toxicity in primary neuronal cultures: Possible risk factors in the Alzheimer’s-type neurodegenerative pathways. Journal of Neurochemestry, 76, 1509–1520.CrossRef White, A. R., Huang, X., Jobling, M. F., Barrow, C. J., Beyreuther, K., Masters, C. L., et al. (2001). Homocysteine potentiates copper- and amyloid beta peptide-mediated toxicity in primary neuronal cultures: Possible risk factors in the Alzheimer’s-type neurodegenerative pathways. Journal of Neurochemestry, 76, 1509–1520.CrossRef
10.
Zurück zum Zitat Hazell, A. S. (2007). Excitotoxic mechanisms in stroke: An update of concepts and treatment strategies. Neurochemistry International, 50, 941–953.CrossRefPubMed Hazell, A. S. (2007). Excitotoxic mechanisms in stroke: An update of concepts and treatment strategies. Neurochemistry International, 50, 941–953.CrossRefPubMed
11.
Zurück zum Zitat Shi, H., & Liu, K. J. (2007). Cerebral tissue oxygenation and oxidative brain injury during ischemia and reperfusion. Frontiers in Bioscience, 12, 1318–1328.CrossRefPubMed Shi, H., & Liu, K. J. (2007). Cerebral tissue oxygenation and oxidative brain injury during ischemia and reperfusion. Frontiers in Bioscience, 12, 1318–1328.CrossRefPubMed
12.
Zurück zum Zitat Zhu, X., Smith, M. A., Honda, K., Aliev, G., Moreira, P. I., Nunomura, A., et al. (2007). Vascular oxidative stress in Alzheimer disease. Journal of the Neurological Sciences, 257, 240–246.CrossRefPubMed Zhu, X., Smith, M. A., Honda, K., Aliev, G., Moreira, P. I., Nunomura, A., et al. (2007). Vascular oxidative stress in Alzheimer disease. Journal of the Neurological Sciences, 257, 240–246.CrossRefPubMed
13.
Zurück zum Zitat Dayal, S., & Lentz, S. R. (2007). Role of redox reactions in the vascular phenotype of hyperhomocysteinemic animals. Antioxidants & Redox Signaling, 11, 1899–1909.CrossRef Dayal, S., & Lentz, S. R. (2007). Role of redox reactions in the vascular phenotype of hyperhomocysteinemic animals. Antioxidants & Redox Signaling, 11, 1899–1909.CrossRef
14.
Zurück zum Zitat Halliwell, B., & Gutteridge, J. M. C. (2007). Free radicals in biology and medicine. New York: Oxford University Press. Halliwell, B., & Gutteridge, J. M. C. (2007). Free radicals in biology and medicine. New York: Oxford University Press.
15.
Zurück zum Zitat Becker, J. S., Adler, A., Schneeberger, A., Huang, H., Wang, Z., Walsh, E., et al. (2005). Hyperhomocysteinemia, a cardiac metabolic disease role of nitric oxide and the p22phox subunit of NADPH oxidase. Circulation, 111, 2112–2118.CrossRefPubMed Becker, J. S., Adler, A., Schneeberger, A., Huang, H., Wang, Z., Walsh, E., et al. (2005). Hyperhomocysteinemia, a cardiac metabolic disease role of nitric oxide and the p22phox subunit of NADPH oxidase. Circulation, 111, 2112–2118.CrossRefPubMed
16.
Zurück zum Zitat Tuteja, N., Chandra, M., Tuteja, R., & Misra, M. K. (2004). Nitric oxide as a unique bioactive signaling messenger in physiology and pathophysiology. Journal of Biomedicine and Biotechnology, 4, 227–237.CrossRef Tuteja, N., Chandra, M., Tuteja, R., & Misra, M. K. (2004). Nitric oxide as a unique bioactive signaling messenger in physiology and pathophysiology. Journal of Biomedicine and Biotechnology, 4, 227–237.CrossRef
17.
Zurück zum Zitat Brosnan, J. T., Jacobs, R. L., Stead, L. M., & Brosnan, M. E. (2004). Methylation demand: A key determinant of homocysteine metabolism. Acta Biochimica Polonica, 51, 405–413.PubMed Brosnan, J. T., Jacobs, R. L., Stead, L. M., & Brosnan, M. E. (2004). Methylation demand: A key determinant of homocysteine metabolism. Acta Biochimica Polonica, 51, 405–413.PubMed
18.
Zurück zum Zitat Siri, P. W., Verhoef, P., & Kok, F. J. (1998). Vitamins B6, B12, and folate: Association with plasma total homocysteine and risk of coronary atherosclerosis. Journal of the American College of Nutrition, 17, 435–441.PubMed Siri, P. W., Verhoef, P., & Kok, F. J. (1998). Vitamins B6, B12, and folate: Association with plasma total homocysteine and risk of coronary atherosclerosis. Journal of the American College of Nutrition, 17, 435–441.PubMed
19.
Zurück zum Zitat Racek, J., Rusnakova, H., Trefil, L., & Siala, K. K. (2005). The influence of folate and antioxidants on homocysteine levels and oxidative stress in patients with hyperlipidemia and hyperhomocysteinemia. Physiological Research, 54, 87–95.PubMed Racek, J., Rusnakova, H., Trefil, L., & Siala, K. K. (2005). The influence of folate and antioxidants on homocysteine levels and oxidative stress in patients with hyperlipidemia and hyperhomocysteinemia. Physiological Research, 54, 87–95.PubMed
20.
Zurück zum Zitat Patro, B. S., Adhikari, S., Mukherjee, T., & Chattopadhyay, S. (2006). Folic acid as a Fenton-modulator: Possible physiological implication. Journal of Medicinal Chemestry, 2, 407–413.CrossRef Patro, B. S., Adhikari, S., Mukherjee, T., & Chattopadhyay, S. (2006). Folic acid as a Fenton-modulator: Possible physiological implication. Journal of Medicinal Chemestry, 2, 407–413.CrossRef
21.
Zurück zum Zitat Matté, C., Scherer, E. B., Stefanello, F. M., Barschak, A. G., Vargas, C. R., Netto, C. A., et al. (2007). Concurrent folate treatment prevents Na+, K+ -ATPase activity inhibition and memory impairments caused by chronic hyperhomocysteinemia during rat development. International Journal of Developmental Neuroscience, 25, 545–552.CrossRefPubMed Matté, C., Scherer, E. B., Stefanello, F. M., Barschak, A. G., Vargas, C. R., Netto, C. A., et al. (2007). Concurrent folate treatment prevents Na+, K+ -ATPase activity inhibition and memory impairments caused by chronic hyperhomocysteinemia during rat development. International Journal of Developmental Neuroscience, 25, 545–552.CrossRefPubMed
22.
Zurück zum Zitat Matté, C., Mackedanz, V., Stefanello, F. M., Scherer, E. B., Andreazza, A. C., Zanotto, C., et al. (2009). Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: Protective effect of folic acid. Neurochemistry International, 54, 7–13.CrossRefPubMed Matté, C., Mackedanz, V., Stefanello, F. M., Scherer, E. B., Andreazza, A. C., Zanotto, C., et al. (2009). Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: Protective effect of folic acid. Neurochemistry International, 54, 7–13.CrossRefPubMed
23.
Zurück zum Zitat Streck, E. L., Matté, C., Vieira, P. S., Rombaldi, F., Wannmacher, C. M. D., Wajner, M., et al. (2002). Reduction of Na+, K+ -ATPase activity in hippocampus of rats subjected to chemically induced hyperhomocysteinemia. Neurochemical Research, 27, 1585–1590.CrossRef Streck, E. L., Matté, C., Vieira, P. S., Rombaldi, F., Wannmacher, C. M. D., Wajner, M., et al. (2002). Reduction of Na+, K+ -ATPase activity in hippocampus of rats subjected to chemically induced hyperhomocysteinemia. Neurochemical Research, 27, 1585–1590.CrossRef
24.
Zurück zum Zitat Lalonde, R., Joyal, C. C., & Botez, M. I. (1993). Effects of folic acid and folinic acid on cognitive and motor behaviors in 20-month-old rats. Pharmacology, Biochemistry and Behavior, 44, 703–707.CrossRef Lalonde, R., Joyal, C. C., & Botez, M. I. (1993). Effects of folic acid and folinic acid on cognitive and motor behaviors in 20-month-old rats. Pharmacology, Biochemistry and Behavior, 44, 703–707.CrossRef
25.
Zurück zum Zitat Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95, 351–358.CrossRefPubMed Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95, 351–358.CrossRefPubMed
26.
Zurück zum Zitat Lebel, C. P., Ischiropoulos, H., & Bondy, S. C. (1992). Evaluation of the probe 2′, 7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chemical Research in Toxicology, 5, 227–231.CrossRefPubMed Lebel, C. P., Ischiropoulos, H., & Bondy, S. C. (1992). Evaluation of the probe 2′, 7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chemical Research in Toxicology, 5, 227–231.CrossRefPubMed
27.
Zurück zum Zitat Marklund, S. L. (1985). Pyrogallol autoxidation. In R. A. Greenwald (ed.), Handbook for oxygen radical research (pp. 243–247). Boca Raton: CRC Press. Marklund, S. L. (1985). Pyrogallol autoxidation. In R. A. Greenwald (ed.), Handbook for oxygen radical research (pp. 243–247). Boca Raton: CRC Press.
29.
Zurück zum Zitat Green, L. C., Wagner, D. A., Glogowski, J., Skipper, P. L., Wishnok, J. S., & Tannenbaum, S. R. (1982). Analysis of nitrate, nitrite and [15 N]nitrate in biological fluids. Analytical Biochemistry, 126, 131–138.CrossRefPubMed Green, L. C., Wagner, D. A., Glogowski, J., Skipper, P. L., Wishnok, J. S., & Tannenbaum, S. R. (1982). Analysis of nitrate, nitrite and [15 N]nitrate in biological fluids. Analytical Biochemistry, 126, 131–138.CrossRefPubMed
30.
Zurück zum Zitat Lowry, O. H., Rosebrough, N. J., Farr, A. L., & RandalL, R. J. (1951). Protein measurement with the folin phenol reagent. Journal of Biological Chemistry, 193, 265–267.PubMed Lowry, O. H., Rosebrough, N. J., Farr, A. L., & RandalL, R. J. (1951). Protein measurement with the folin phenol reagent. Journal of Biological Chemistry, 193, 265–267.PubMed
31.
Zurück zum Zitat Perry, D. J. (1999). Hyperhomocysteinemia. Baillieres Clinical Haematology., 12, 451–477. Perry, D. J. (1999). Hyperhomocysteinemia. Baillieres Clinical Haematology., 12, 451–477.
32.
Zurück zum Zitat Eikelboom, J. W., Lonn, E., Genest, J., Jr., Hankey, G. J., & Yusuf, S. (1999). Homocyst(e)ine and cardiovascular disease: A critical review of the epidemiologic evidence. Annals of Internal Medicine, 131, 363–375.PubMed Eikelboom, J. W., Lonn, E., Genest, J., Jr., Hankey, G. J., & Yusuf, S. (1999). Homocyst(e)ine and cardiovascular disease: A critical review of the epidemiologic evidence. Annals of Internal Medicine, 131, 363–375.PubMed
33.
Zurück zum Zitat Tavares, J. R., D’almeida, V., Diniz, D. C., Terzi, C. A., Cruz, E. N., Stefani, E., et al. (2002). Analisis of plasma homocysteine levels in patients with unstable angina. Arquivos Brasileiros de Cardiologia, 79, 167–172.CrossRef Tavares, J. R., D’almeida, V., Diniz, D. C., Terzi, C. A., Cruz, E. N., Stefani, E., et al. (2002). Analisis of plasma homocysteine levels in patients with unstable angina. Arquivos Brasileiros de Cardiologia, 79, 167–172.CrossRef
34.
Zurück zum Zitat Dias, P. M. T., Mezzomo, A., Peteffi, C., & Pezzi, D. R. (2001). Homocisteína: Um fator de risco vascular. Revista Científica da AMECS, 1, 53–58. Dias, P. M. T., Mezzomo, A., Peteffi, C., & Pezzi, D. R. (2001). Homocisteína: Um fator de risco vascular. Revista Científica da AMECS, 1, 53–58.
35.
Zurück zum Zitat Lemieux, H., Bulteau, A. L., Friguet, B., Tardif, J. C., Blier, P. U. (2010). Dietary fatty acids and oxidative stress in the heart mitochondria. Mitochondrion, in press. Lemieux, H., Bulteau, A. L., Friguet, B., Tardif, J. C., Blier, P. U. (2010). Dietary fatty acids and oxidative stress in the heart mitochondria. Mitochondrion, in press.
36.
Zurück zum Zitat Pillai, V. B., Sundaresan, N. R., Jeevanandam, V., & Gupta, M. P. (2010). Mitochondrial SIRT3 and heart disease. Cardiovascular Research, 88, 250–256.CrossRefPubMed Pillai, V. B., Sundaresan, N. R., Jeevanandam, V., & Gupta, M. P. (2010). Mitochondrial SIRT3 and heart disease. Cardiovascular Research, 88, 250–256.CrossRefPubMed
37.
Zurück zum Zitat Stehr, C. B., Mellado, R., Ocaranza, M. P., Carvajal, C. A., Mosso, L., Becerra, E., et al. (2010). Increased levels of oxidative stress, subclinical inflammation, and myocardial fibrosis markers in primary aldosteronism patients. Journal of Hypertension, 28, 2120–2126.PubMed Stehr, C. B., Mellado, R., Ocaranza, M. P., Carvajal, C. A., Mosso, L., Becerra, E., et al. (2010). Increased levels of oxidative stress, subclinical inflammation, and myocardial fibrosis markers in primary aldosteronism patients. Journal of Hypertension, 28, 2120–2126.PubMed
38.
Zurück zum Zitat Misra, M. K., Sarwat, M., Bhakuni, P., Tuteja, R., & Tuteja, N. (2009). Oxidative stress and ischemic myocardial syndromes. Medical Science Monitor, 15, 209–219. Misra, M. K., Sarwat, M., Bhakuni, P., Tuteja, R., & Tuteja, N. (2009). Oxidative stress and ischemic myocardial syndromes. Medical Science Monitor, 15, 209–219.
39.
Zurück zum Zitat Radi, R., Turrens, J. F., Chang, L. Y., Bush, K. M., Crapo, J. D., & Freeman, B. A. (1991). Detection of catalase in rat heart mitochondria. The Journal of Biological Chemistry, 226, 22028–22034. Radi, R., Turrens, J. F., Chang, L. Y., Bush, K. M., Crapo, J. D., & Freeman, B. A. (1991). Detection of catalase in rat heart mitochondria. The Journal of Biological Chemistry, 226, 22028–22034.
40.
Zurück zum Zitat Dayal, S., Arning, E., Bottiglieri, T., Boger, R. H., Sigmund, C. D., Faraci, F. M., et al. (2004). Cerebral vascular dysfunction mediated by superoxide in hyperhomocysteinemic mice. Stroke, 35, 1957–1962.CrossRefPubMed Dayal, S., Arning, E., Bottiglieri, T., Boger, R. H., Sigmund, C. D., Faraci, F. M., et al. (2004). Cerebral vascular dysfunction mediated by superoxide in hyperhomocysteinemic mice. Stroke, 35, 1957–1962.CrossRefPubMed
41.
Zurück zum Zitat Faraci, F. M., & Lentz, S. R. (2004). Hyperhomocysteinemia, oxidative stress, and cerebral vascular dysfunction. Stroke, 35, 345–347.CrossRefPubMed Faraci, F. M., & Lentz, S. R. (2004). Hyperhomocysteinemia, oxidative stress, and cerebral vascular dysfunction. Stroke, 35, 345–347.CrossRefPubMed
42.
Zurück zum Zitat Nappo, F., De Rosa, N., Marfella, R., De Lucia, D., Ingrosso, D., Perna, A. F., et al. (1999). Impairment of endothelial functions by acute hyperhomocysteinemia and reversal by antioxidant vitamins. Journal of the American Medical Association, 22, 2113–2118.CrossRef Nappo, F., De Rosa, N., Marfella, R., De Lucia, D., Ingrosso, D., Perna, A. F., et al. (1999). Impairment of endothelial functions by acute hyperhomocysteinemia and reversal by antioxidant vitamins. Journal of the American Medical Association, 22, 2113–2118.CrossRef
43.
Zurück zum Zitat Tsai, J. C., Perrella, M. A., Yoshizumi, M., Hsieh, C. M., Haber, E., Schlegel, R., et al. (1994). Promotion of vascular smooth muscle cell growth by homocysteine: A link to atherosclerosis. Proceedings of the National Academy of Sciences, 91, 6369–6373.CrossRef Tsai, J. C., Perrella, M. A., Yoshizumi, M., Hsieh, C. M., Haber, E., Schlegel, R., et al. (1994). Promotion of vascular smooth muscle cell growth by homocysteine: A link to atherosclerosis. Proceedings of the National Academy of Sciences, 91, 6369–6373.CrossRef
44.
Zurück zum Zitat Wang, H., Yoshizumi, M., Lai, K., Tsai, J. C., Perrella, M. A., Haber, E., et al. (1997). Inhibition of growth and p21ras methylation in vascular endothelial cells by homocysteine but not cysteine. The Journal of Biological Chemistry, 272, 25380–25385.CrossRefPubMed Wang, H., Yoshizumi, M., Lai, K., Tsai, J. C., Perrella, M. A., Haber, E., et al. (1997). Inhibition of growth and p21ras methylation in vascular endothelial cells by homocysteine but not cysteine. The Journal of Biological Chemistry, 272, 25380–25385.CrossRefPubMed
45.
Zurück zum Zitat Tang, L., Mamotte, C. D., Van Bockxmeer, F. M., & Taylor, R. R. (1998). The effect of homocysteine on DNA synthesis in cultured human vascular smooth muscle. Atherosclerosis, 136, 169–173.CrossRefPubMed Tang, L., Mamotte, C. D., Van Bockxmeer, F. M., & Taylor, R. R. (1998). The effect of homocysteine on DNA synthesis in cultured human vascular smooth muscle. Atherosclerosis, 136, 169–173.CrossRefPubMed
46.
Zurück zum Zitat Zhang, X., Li, H., Jin, H., Ebin, Z., Brodsky, S., & Goligorsky, M. S. (2000). Effects of homocysteine on endothelial nitric oxide production. American Journal of Physiology-Renal Physiology, 279, 671–678. Zhang, X., Li, H., Jin, H., Ebin, Z., Brodsky, S., & Goligorsky, M. S. (2000). Effects of homocysteine on endothelial nitric oxide production. American Journal of Physiology-Renal Physiology, 279, 671–678.
47.
Zurück zum Zitat Cai, H., & Harrison, D. G. (2000). Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress. Circulation Research, 87, 840–844.PubMed Cai, H., & Harrison, D. G. (2000). Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress. Circulation Research, 87, 840–844.PubMed
48.
Zurück zum Zitat Lang, D., Kredan, M. B., Moat, S. J., Hussain, S. A., Powell, C. A., Bellamy, M. F., et al. (2000). Homocysteine-induced inhibition of endothelium-dependent relaxation in rabbit aorta: Role for superoxide anions. Arteriosclerosis, Thrombosis, and Vascular Biology, 20, 422–427.PubMed Lang, D., Kredan, M. B., Moat, S. J., Hussain, S. A., Powell, C. A., Bellamy, M. F., et al. (2000). Homocysteine-induced inhibition of endothelium-dependent relaxation in rabbit aorta: Role for superoxide anions. Arteriosclerosis, Thrombosis, and Vascular Biology, 20, 422–427.PubMed
49.
Zurück zum Zitat MacCarthy, P. A., Grieve, D. J., Li, J. M., Dunster, C., Kelly, F. J., & Shah, A. M. (2001). Impaired endothelial regulation of ventricular relaxation in cardiac hypertrophy: Role of reactive oxygen species and NADPH oxidase. Circulation, 104, 2967–2974.CrossRefPubMed MacCarthy, P. A., Grieve, D. J., Li, J. M., Dunster, C., Kelly, F. J., & Shah, A. M. (2001). Impaired endothelial regulation of ventricular relaxation in cardiac hypertrophy: Role of reactive oxygen species and NADPH oxidase. Circulation, 104, 2967–2974.CrossRefPubMed
50.
Zurück zum Zitat Massion, P., Feron, O., Dessy, C., & Balligand, J. (2003). Nitric oxide and cardiac function: Ten years after, and continuing. Circulation Research, 93, 388–398.CrossRefPubMed Massion, P., Feron, O., Dessy, C., & Balligand, J. (2003). Nitric oxide and cardiac function: Ten years after, and continuing. Circulation Research, 93, 388–398.CrossRefPubMed
51.
Zurück zum Zitat Casadei, B. (2006). The emerging role of neuronal nitric oxide synthase in the regulation of myocardial function. Experimental Physiology, 91, 943–955.CrossRefPubMed Casadei, B. (2006). The emerging role of neuronal nitric oxide synthase in the regulation of myocardial function. Experimental Physiology, 91, 943–955.CrossRefPubMed
52.
Zurück zum Zitat Beckman, J. S., & Koppenol, W. H. (1996). Nitric oxide, superoxide, and peroxynitrite: The good, the bad, and ugly. American Journal of Physiology, 271, 1424–1437. Beckman, J. S., & Koppenol, W. H. (1996). Nitric oxide, superoxide, and peroxynitrite: The good, the bad, and ugly. American Journal of Physiology, 271, 1424–1437.
53.
Zurück zum Zitat Joshi, R., Adhikari, S., Patro, B. S., Chattopadhyay, S., & Mukherjee, T. (2001). Free radical scavenging behavior of folic acid: Evidence for possible antioxidant activity. Free Radical Biology and Medicine, 30, 1390–1399.CrossRefPubMed Joshi, R., Adhikari, S., Patro, B. S., Chattopadhyay, S., & Mukherjee, T. (2001). Free radical scavenging behavior of folic acid: Evidence for possible antioxidant activity. Free Radical Biology and Medicine, 30, 1390–1399.CrossRefPubMed
54.
Zurück zum Zitat Au-Yeung, K. K. W., Yip, J. C. W., Siow, Y. L., & Karmin, O. (2006). Folic acid inhibits homocysteine-induced superoxide anion production and nuclear factor kappa B activation in macrophages. Canadian Journal of Physiology and Pharmacology, 84, 141–147.CrossRefPubMed Au-Yeung, K. K. W., Yip, J. C. W., Siow, Y. L., & Karmin, O. (2006). Folic acid inhibits homocysteine-induced superoxide anion production and nuclear factor kappa B activation in macrophages. Canadian Journal of Physiology and Pharmacology, 84, 141–147.CrossRefPubMed
55.
56.
Zurück zum Zitat Antoniades, C., Shirodaria, C., Warrick, N., Cai, S., de Bono, J., Lee, J., et al. (2006). 5-Methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: Effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling. Circulation, 114, 1193–1201.CrossRefPubMed Antoniades, C., Shirodaria, C., Warrick, N., Cai, S., de Bono, J., Lee, J., et al. (2006). 5-Methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: Effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling. Circulation, 114, 1193–1201.CrossRefPubMed
57.
Zurück zum Zitat Willett, W. C. (1985). Does low vitamin B6 intake increase the risk of coronary heart disease? “Vitamin B6: Its Role in Health and Disease”. Boston: Alan R. Liss, Inc. Willett, W. C. (1985). Does low vitamin B6 intake increase the risk of coronary heart disease? “Vitamin B6: Its Role in Health and Disease”. Boston: Alan R. Liss, Inc.
58.
Zurück zum Zitat Verhoef, P., Stampfer, M. J., Buring, J. E., Gaziano, J. M., Allen, R. H., Stabler, S. P., et al. (1996). Homocysteine metabolism and risk of myocardial infarction: Relationship with vitamins B6, B12 and folate. American Journal of Epidemiology, 143, 845–859.PubMed Verhoef, P., Stampfer, M. J., Buring, J. E., Gaziano, J. M., Allen, R. H., Stabler, S. P., et al. (1996). Homocysteine metabolism and risk of myocardial infarction: Relationship with vitamins B6, B12 and folate. American Journal of Epidemiology, 143, 845–859.PubMed
59.
Zurück zum Zitat Lugue, C. D., Vargas, R. H., Romo, E., Rios, A., & Escalante, B. (2006). The role of nitric oxide in the post-ischemic revascularization process. Pharmacology &Therapeutics, 112, 553–563.CrossRef Lugue, C. D., Vargas, R. H., Romo, E., Rios, A., & Escalante, B. (2006). The role of nitric oxide in the post-ischemic revascularization process. Pharmacology &Therapeutics, 112, 553–563.CrossRef
60.
Zurück zum Zitat Bloor, J., Shukla, N., Smith, F. C., Angelini, G. D., & Jeremy, J. Y. (2010). Folic acid administration reduces neointimal thickening, augments neo-vasa vasorum formation and reduces oxidative stress in saphenous vein grafts from pigs used as a model of diabetes. Diabetologia, 53, 980–988.CrossRefPubMed Bloor, J., Shukla, N., Smith, F. C., Angelini, G. D., & Jeremy, J. Y. (2010). Folic acid administration reduces neointimal thickening, augments neo-vasa vasorum formation and reduces oxidative stress in saphenous vein grafts from pigs used as a model of diabetes. Diabetologia, 53, 980–988.CrossRefPubMed
Metadaten
Titel
Homocysteine Induces Oxidative–Nitrative Stress in Heart of Rats: Prevention by Folic Acid
verfasst von
Janaína Kolling
Emilene B. Scherer
Aline Andrea da Cunha
Maira Jaqueline da Cunha
Angela T. S. Wyse
Publikationsdatum
01.03.2011
Verlag
Humana Press Inc
Erschienen in
Cardiovascular Toxicology / Ausgabe 1/2011
Print ISSN: 1530-7905
Elektronische ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-010-9094-7

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