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Antioxidant activity of vitamin B6 delays homocysteine-induced atherosclerosis in rats

Published online by Cambridge University Press:  08 March 2007

Naoko Endo
Affiliation:
Department of Veterinary PhysiologyFaculty of AgricultureKagoshima University1-21-24 KorimotoKagoshima 890-0065Japan
Kazuo Nishiyama
Affiliation:
Department of BiochemistryFaculty of AgricultureMiyazaki University1-1 Gakuenkibanadai NishiMiyazaki 889-2192Japan
Akira Otsuka
Affiliation:
Department of Nutritional Biochemistry and Feed ChemistryFaculty of AgricultureKagoshima University1-21-24 KorimotoKagoshima 890-0065Japan
Hiroaki Kanouchi
Affiliation:
Department of BiochemistryKawasaki Medical School577 MatsushimaKurashiki 701-0192Japan
Masaki Taga
Affiliation:
Department of Applied Clinical NutritionKitasato Junior College of Health and Hygienic Sciences500 YamatoMinamiUonuma 949-7300Japan
Tatsuzo Oka*
Affiliation:
Department of BiochemistryFaculty of AgricultureMiyazaki University1-1 Gakuenkibanadai NishiMiyazaki 889-2192Japan
*
*Corresponding author: Dr Tatsuzo Oka, fax +81 99 285 8714, Email [email protected]
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Abstract

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Elevated plasma homocysteine is a risk factor for atherosclerotic disease. In the present study, we have examined whether the oxidative stress due to a low level of vitamin B6 accelerates the development of homocysteine-induced atherosclerosis in rats. First, the effect of homocysteine thiolactone intake (50mg/kgperd) on vascular integrity, lipid peroxide concentration, endothelial NO synthase (eNOS) expression and biochemical profiles was examined at day 1, day 21 and day 42 (five rats per group). The histochemical staining ofthe rat aorta showed no change at day 1 and day 21, but the subendothelial space was observed to be enlarged in rat aorta at day 42 with exposure to homocysteine thiolactone. Expression of eNOS was observed in rat aorta at day 42, but not at day 1 and day 21. Serum lipid peroxide concentration and biochemical profiles including glucose cholesterol and triacylglycerol showed no change at any day. Second, the effect of homocysteine thiolactone intake in the presence and absence of vitamin B6 on vascular integrity was examined at day 1 and day 14 (five rats per group). Aortic lesions were observed in vitamin B6-deficient rat aorta at day 14 but not in vitamin B6-supplemented rats. The expression of eNOS was also observedin vitamin B6-deficient rat aorta at day 14. Serum lipid concentrations of the vitamin B6-deficient group significantly increased compared with concentrations of the vitamin B6-supplemented group, though serum concentration of homocysteine did not change between both groups. These results suggest that the oxidative stress caused by a low level of vitamin B6 accelerates the development of homocysteine-induced atherosclerosis in rats.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2006

References

Adachi, H, Hirai, Y, Fujiura, Y, Matsuoka, H, Satoh, A & Imaizumi, TPlasma homocysteine levels and atherosclerosis in Japan: epidemiological study by use of carotid ultrasonography. Stroke 2002 33 21772181Google Scholar
Barua, RS, Ambrose, JA, Srivastava, S, DeVoe, MC & Eales-Reynolds, LJReactive oxygen species are involved in smokinginduced dysfunction of nitric oxide biosynthesis and upregulation of endothelial nitric oxide synthase: an in vitro demonstration in human coronary artery endothelial cells. Circulation 2003 107 23422347Google Scholar
Bellamy, MF, McDowell, IF, Ramsey, MW, Brownlee, M, Newcombe, RG & Lewis, MJOral folate enhances endothelial function in hyperhomocysteinaemic subjects. Eur J Clin Invest 1999 29 659662Google Scholar
Brattstrom, L & Wilcken, DELHomocysteine and cardiovascular disease: cause or effect?. Am J Clin Nutr 2000 72 315323Google Scholar
Chambers, JC, Obeid, OA & Kooner, JSPhysiological increments in plasma homocysteine induce vascular endothelial dysfunction in normal human subjects. Arterioscler Thromb Vasc Biol 1999 19 29222927Google Scholar
Chen, H & Xiong, LPyridoxine is required for post-embryonic root development and tolerance to osmotic and oxidant stresses. Plant J 2005 44 396408Google Scholar
Coburn, SP, Mahuren, JD, Schaltenbrand, WE, Wostmann, BS & Madsen, DEffects of vitamin B-6 deficiency and 40-deoxypyridoxine on pyridoxal phosphate concentrations, pyridoxine kinase and other aspects of metabolism in the rat. J Nutr 1981 111 391398Google Scholar
Ehrenshaft, M, Bilski, P, Li, MY, Chignell, CF & Daub, MA highly conserved sequence is a novel gene involved in de novo vitamin B6 biosynthesis. Proc Natl Acad Sci U S A 1999 96 93749378Google Scholar
Eikelboom, JW, Lonn, E, Genest, J Jr, Hankey, G & Yusuf, SHomocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med 1999 131 363375Google Scholar
Graham, IM, Daly, LE, Refsum, HMet al.. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA 1997 277 17751781Google Scholar
Hankey, GJ & Eikelboom, JWHomocysteine and vascular disease. Lancet 1999 354 407413Google Scholar
Hansson, GKImmune mechanisms in atherosclerosis. Arterioscler Thromb Vasc Biol 2001 21 18761890Google Scholar
Harker, LA, Ross, R, Slichter, SJ & Scott, CRHomocysteineinduced arteriosclerosis: the role of endothelial cell injury and platelet response in its genesis. J Clin Invest 1976 58 731741Google Scholar
Hofmann, MA, Lalla, E, Lu, Y. Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model. J Clin Invest 2001 107 675683Google Scholar
Loscalzo, JThe oxidant stress of hyperhomocysteinemia. J Clin Invest 1996 98 57Google Scholar
McCully, KSVascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969 56 111128Google Scholar
Miller, JW, Ribaya-Mercado, JD, Russell, RM, Shepard, DC, Morrow, FD, Cochary, EF, Sadowski, JA, Gershoff, SN & Selhub, JEffect of vitamin B-6 deficiency on fasting plasma homocysteine concentrations. Am J Clin Nutr 1992 55 11541160Google Scholar
Okada, M & Ochi, AThe effect of dietary level on transaminase activities and fat deposition in vitamin B6-deficient rat liver. J Biochem 1971 70 581585Google Scholar
Refsum, H, Smith, AD, Ueland, PMet al.. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 2004 50 332Google Scholar
Rimm, EB, Willett, WC, Hu, FB, Sampson, L, Colditz, GA, Manson, JE, Hennekens, C & Stampfer, MJFolate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 1998 279 359364Google Scholar
Robinson, K, Mayer, EL, Miller, DPet al. Hyperhomocysteinemia and low pyridoxal phosphate: common and independent reversible risk factors for coronary artery disease. Circulation 1995 92 28252830Google Scholar
Ross, RThe pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993 362 801809Google Scholar
Ross, RAtherosclerosis - an inflammatory disease. N Engl J Med 1999 340 115126Google Scholar
Silverman, MD, Tumuluri, RJ, Davis, M, Lopez, G, Rosenbaum, JT & Lelkes, PIHomocysteine upregulates vascular cell adhesion molecule-1 expression in cultured human aortic endothelial cells and enhances monocyte adhesion. Arterioscler Thromb Vasc Biol 2002 22 587592Google Scholar
Siri, PW, Verhoef, P & Kok, FJVitamins B6, B12, and folate:association with plasma total homocysteine and risk of coronary atherosclerosis. J Am Col Nutr 1998 17 435441Google Scholar
Stocker, P, Lesgards, JF, Vidal, N, Chalier, F & Prost, MESR study of a biological assay on whole blood: antioxidant efficiency of various vitamins. Biochim Biophys Acta 2003 1621 18Google Scholar
Taylor, LM Jr, DeFrang, RD, Harris, EJ Jr & Porter, JMThe association of elevated plasma homocyst(e)ine with progression of symptomatic peripheral arterial disease. J Vasc Surg 1991 13 128136Google Scholar
Tryfiates, GPVitamin B6 Metabolism and Role in Growth. Westport, CT: Food and Nutrition Press 1980Google Scholar
Ubbink, JBVitamin nutrition status and homocysteine: an atherogenic risk factor. Nutr Rev 1994 52 383387Google Scholar
Ueland, PM, Refsum, H, Beresford, SAA & Vollset, SEThe controversy over homocysteine and cardiovascular risk. Am J Clin Nutr 2000 72 324332Google Scholar
Ullegaddi, R, Powers, HJ & Gariballa, SEB-group vitamin supplementation mitigates oxidative damage after acute ischemic stroke. Clin Sci 2004 107 477484Google Scholar
van Aken, BE, Jansen, J, Van Deventer, SJH & Reitsma, PHElevated levels of homocysteine increase IL-6 production in monocytic Mono Mac 6 cells. Blood Coagul Fibrinolysis 2000 11 159164Google Scholar
van den Bosch, MAAJ, Bloemenkamp, DGM, Mali, WPTM, Kemmeren, JM, Tanis, BC, Algra, A, Rosendaal, FR & van der Graaf, YHyperhomocysteinemia and risk for peripheral arterial occlusive disease in young women. J Vasc Surg 2003 38 772778Google Scholar
Verhoef, P, Kok, FJ, Kruyssen, DACM, Schouten, EG, Witteman, JCM, Grobbee, DE, Ueland, PM & Refsum, HPlasma total homocysteine, B vitamins, and risk of coronary atherosclerosis. Arterioscler Thromb Vasc Biol 1997 17 989995Google Scholar
Verhoef, P, Stampfer, MJ, Buring, JE, Gaziano, JM, Allen, RH, Stabler, SP, Reynolds, RD, Kok, FJ, Hennekens, CH & Willett, WCHomocysteine metabolism and risk of myocardial infarction:relation with vitamins B6, B12, and folate. Am J Epidemiol 1996 143 845859Google Scholar
Vollset, SE, Refsum, H, Tverdal, A, Nygard, O, Nordrehaug, JE, Tell, GS & Ueland, PMPlasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocysteine Study. Am J Clin Nutr 2001 74 130136Google Scholar