臺灣博碩士論文加值系統

本研究目的在探討葉酸缺乏飲食對餵予正常及高脂飲食之大白鼠其體內抗氧化防禦系統及脂質代謝之影響。實驗設計如下，將32隻雄性離乳Spraque-Dawley大白鼠隨機分成兩組，分別給予正常及調高一倍油脂含量之AIN-93G飼料，再將各組分別餵予含4.5μmol/公斤飼料之葉酸為對照組；不含葉酸為實驗組，並添加1%之葉酸生成抑制劑（succinylsulfa thiazole），以抑制腸道中微生物生成葉酸。實驗為期8週，觀察其生長情形，並比較各組間抗氧化防禦系統及血脂質之變化。結果顯示，給予正常葉酸含量之高脂飲食組其累積攝食量為1149.4±20.2g，較正常飲食組之958.5±40.7g為低(P＜0.05)，但其累積體重(364.5±14.9g)卻較正常組(312.5±11.9g)為高(P＜0.05)。累積排便量為63.9±2.6g低於正常飲食之葉酸正常組68.7±2.5g (P＜0.05)，而累積撥食量及累積飲水量則無差異。但葉酸缺乏對兩種飲食動物生長狀況並無影響。葉酸缺乏時高脂飲食及正常飲食血清葉酸濃度分別3.7±0.3ng/ml及4.2±0.2ng/ml(P＜0.05)，較葉酸正常時為低(82.2±4.4ng/ml及72.7±3.5ng/ml)，確定已達葉酸缺乏狀態，且同半胱胺酸亦隨葉酸降低而升高(P＜0.05)，高脂飲食及正常飲食組分別為19.7±2.3ng/ml及11.1±0.7ng/ml，且高脂飲食之葉酸缺乏組其同半胱胺酸值較正常飲食之葉酸缺乏組高（P<0.05）。另外，無論葉酸缺乏與否高脂飲食組都有較低之血漿胱胺酸值（P<0.05）與較高之麩胱甘值（P<0.05）。在抗氧化系統方面，雖然正常飲食之葉酸缺乏組之GSH含量不變，但GSSG含量增加（P<0.05），且麩胱甘還原活性下降（P<0.05），所以葉酸缺乏組之GSH：GSSG比值3.8±0.2較葉酸正常組5.0±3.8為低（P<0.05），會導致肝中脂質過氧化物上(P<0.05）。而高脂飲食之葉酸缺乏組其GSH含量降低（P<0.05），但GSSG含量不變，麩胱甘過氧化及麩胱甘還原活性上升（P<0.05），且GSH：GSSG比值5.0±0.3不變，因此未造成血漿及肝中脂質過氧化物上升。而葉酸缺乏與否並無對維生素C及E濃度造成影響，但高脂飲食組之血漿維生素C濃度較正常飲食組為高（P<0.05）。在脂質代謝方面，在餵予正常及高脂飲食下，葉酸缺乏對其血清三酸甘油酯、總膽固醇、HDL及LDL濃度並無影響。但高脂飲食組之LDL濃度較正常飲食組低（P<0.05）。且高脂飲食之葉酸缺乏組之肝中總膽固醇濃度90.0±8.3mg/dl較葉酸正常組43.8±4.5mg/dl為高（P<0.05）。而在葉酸缺乏時無論正常飲食及高脂飲食組均有較高之糞便水分（P<0.05），較低之脂質含量（P<0.05）。且正常飲食之葉酸缺乏組其糞便中性固醇低於葉酸正常組（P<0.05）。葉酸缺乏不會對動物之其他血液檢測值造成影響，但高之飲食之葉酸缺乏其紅血球數目、血色素及血比容均低於正常飲食之葉酸缺乏組（P<0.05）。
綜合以上結果得知，當給予Spraque-Dawley大白鼠葉酸缺乏飲食時，隨體內葉酸含量降低會導致同半胱胺酸蓄積，且葉酸缺乏可能會影響抗氧化防禦系統及脂質代謝，但機轉未明。

The objective of this study was to investigate the effects between normal or high fat diet on antioxidant defense system and lipid metabolism in folate deficiency rats. Weanling male Spraque-Dawley rats were fed normal 16% fat content and 30% fat content with 0 or 4.5μmol folic acid/kg diet for 8 weeks. To inhibit GI microflora produced folate, 1% succinylsulfathiazole was added to the folate deficient diet. The results indicated that when fed normal folate diet, cumulative food intake of high fat diet was 1149.35±20.17g. The data was lower than in normal diet group (68.8±2.5g) (P<0.05). However, cumulative body weight (364.5±14.9g) was higher than normal diet group (312.5±11.9g) (P<0.05). Cumulative stool amount (63.9±2.6g) was lower than normal diet with normal folate group (68.7±2.5g) (P<0.05). In addition, there was no different of cumulative food spilled and cumulative water consumed among groups. Whether fed normal or high fat diet, the folate condition did not influence growth status. When folate deficiency, serum folate concentration of high fat diet and normal diet was 3.7±0.3ng/ml and 4.2±0.2ng/ml. The data were lower than normal folate group (82.2±4.4ng/ml, 72.7±3.5ng/ml) (P<0.05). While homocysteine level significant increased (P<0.05) with folate decrease. Homocysteine level of high fat diet and normal diet group was 19.7±2.3μM and 11.1±0.7μM, and homocysteine level of high fat diet group was higher than normal diet group in folate-deficient rats. (P<0.05). When feeding high fat diet whether folate exist or not, all had low plasma cysteine (P<0.05) and high glutathione level (P<0.05). Although, when feeding normal diet to folate-deficient rat had high GSSG (P<0.05), glutathione reductase activity was decrease (P<0.05). The GSH level remain the same. Therefore, GSH: GSSG ratio (3.8±0.2) was decreased in folate deficiency group (5.0±3.8) (P<0.05) and lipid peroxidative compound of liver were increased (P<0.05). In addition, when feeding high fat diet to folate-deficient rat had low GSH level (P<0.05), while glutathione peroxidase and glutathione reductase activity were increased (P<0.05). The GSSG level and GSH: GSSG ratio (5.0±0.3 and 4.8±0.6) was remained in same level. It causing lipid peroxidative compound was no increased of plasma and liver. Although, the folate deficiency did not affect plasma and liver vitamin C and E, while the plasma vitamin C in high fat diet group were higher than normal diet group (P<0.05). When fed normal and high fat diet, folate deficient did not affect serum triglycerode, total cholesterol, HDL and LDL. In addition, total cholesterol concentration was 90.0±8.3mg/dl of high fat diet with folate deficiency group, and the amount of normal folate group (43.8±4.5mg/dl) was increased (P<0.05). However, there were higher moisture in stool (P<0.05), and lower stool fat (P<0.05) of high fat diet and normal diet when feeding folate deficiency diet. Moreover, folate deficient group had lower sterol level in stool than normal folate content group in normal diet (P<0.05). In addition, the other blood variable compounds was no different in folate- deficient rats. However, high fat diet group had lower erythrocyte number, hemogolbin and hematocrit than normal diet group (P<0.05).
In conclusion, homocysteine level significantly increased in folate deficiency Spraque-Dawley rats. Folate deficiency may affect on enzyme antioxidant defense system and lipid metabolism. However, the mechanism still unknown.

目錄
頁次
中文摘要…………………………...…………………………...i
英文摘要……………...….…………………….…….…...…...iii
誌謝………………………………..…………………………...v
目錄…………………………………………………….……...vi
表目錄…………………………………………………………ix
圖目錄……………………………………………………….....x
縮寫表…………………………………………………………xi
第一章前言……………………………………………….…...1
第二章 文獻回顧………………………………………….…..3
第一節葉酸簡介…………………………………………..3
一、葉酸之結構與來源……………………………..…3
二、葉酸參與之生化反應…………………………..…4
第二節 葉酸與疾病之關係………………………………..5
一、葉酸與神經管缺陷症之關係…………………..…5
二、葉酸與心血管疾病之關係……………………..…6
第三節 葉酸與抗氧化防禦系統及脂質之關係….……….7
一、氧化壓力與抗氧化防禦系統…………………….7
(一)非酵素性抗氧化防禦系統…….……………….8
(二)酵素性抗氧化防禦系統……….……………….9
(三)脂質過氧化作用………………………………10
二、葉酸與抗氧化防禦系統之關係…………………10
三、葉酸與脂質之關係……………………………....11
第四節 實驗目的………………………………………...12
第三章 材料與方法………………………………………….16
第一節 實驗設計…………………………………….…..16
第二節 抗氧化防禦系統之分析…………………….…..17
一、非酵素性抗氧化防禦系統………………………17
(一)維生素C之分析……………………………...17
(二)維生素E之分析……………………………...18
(三)氧化及還原型麩胱甘……………………...19
二、酵素性抗氧化防禦系統…………………………19
(一)麩胱甘過氧化…..……………………....20
(二)麩胱甘還原……………………………..20
(三)超氧歧化…………………………………..20
三、脂質過氧化物之分析…………………………….21
第三節 脂質之分析………………………………….…..22
一、血脂質之分析……………………………………22
(一)總膽固醇之分析………………………….......22
(二)三酸甘油酯之分析……………………..…….22
(三)高密度脂蛋白之分析………………………...23
(四)低密度脂蛋白之分析……………………...…23
二、肝臟中脂質之分析………………………………23
三、糞便中脂質之分析………………………………24
(一)糞便水份之分析……………………………..24
(二)糞便粗脂肪之分析…………………………..24
(三)糞便中性固醇之分析………………………..24
第四節 其他血液之檢測………………………………...25
一、葉酸之分析…………………………………….…25
二、含硫化合物之分析………………………………25
三、其他常規血液檢測值之分析……………………26
(一)紅血球、白血球、血小板計數………………26
(二)血紅素之分析…………………..………...…..27
(三)白血球分類之分析…………………………...27
(四)血球比容之分析...………………………..…..28
(五)麩胺酸草醋酸氨基轉移之分析…………...28
(六)麩胺酸丙酮酸氨基轉移之分析…………...28
第五節統計分析…………………………………….…...29
第四章結果………………………………………………34
第一節 生長狀況之變化……………..……………….…34
第二節 血清葉酸及含硫化合物之變化………………...35
第三節 抗氧化防禦系統之變化………………………...36
一、非酵素性抗氧化防禦系統之變化………………36
二、酵素性抗氧化防禦系統之變化…………………37
三、脂質過氧化物之變化……………………………38
第四節 脂質代謝之變化..……..………………….……..38
一、血脂質之變化……………………………………38
二、肝中脂質之變化…………………………………38
三、糞便中脂質之變化………………………………39
第五節 常規血液檢測值………………………………...40
第五章 討論………………………………………………….56
第一節生長狀況之影響…………….………………...56
第二節 葉酸含量及含硫化合物之影響…………….…..59
第三節 抗氧化防禦系統之影響…………………….…..54
一、非酵素性抗氧化防禦系統………………………62
二、酵素性抗氧化防禦系統…………………………63
三、脂質過氧化物……………………………………64
第四節 脂質代謝之影響…………………………….…..64
一、血脂質……………………………………………64
二、肝中脂質…………………………………………65
三、糞便中脂質……………………………………….67
第五節 常規血液檢測值之影響…………………….…..67
參考文獻……………………………………………………...73

行政院衛生署（1993）每日營養建議攝取量及其說明，pp.77-83。
黃伯超、游素玲（1992）營養學精要，pp. 161-164，健康文化事業股份 有限公司編印，台北市。
許玉卿和許瑞芬（1999） 邊緣性葉酸缺乏對F344大白鼠葉酸營養狀態，肝臟抗氧化能力及脂質過氧化傷害之影響。中華營誌 24: 228-240。
段盛秀（1996）食品化學實驗， pp. 10-26，藝軒出版社，台北市。
Aerts, L. A. G. J. M. van, Klaasboer, H. H. & Postma, N. S. (1993) Stereo specific in vitro embryotoxicity of L-homocysteine in pre and post-implantation rodent embryos. Toxicol in Vitro 7: 743-749.
Akesson, B. (1978) Effect of vitamin B12 deficiency on phosphatidyl- ethanolamine methylation in rat liver. Br. J. Nutr. 40: 521-527.
Akesson, B., Fehling, C., Jagerstad, M & Stenaram, V. (1982) Effect of experimental folate deficiency on lipid metabolism in liver and brain. Br. J. Nutr. 47: 505-520.
Allard, J. P., Royall, D., Kurian, R., Muggli, R. & Jeejeebhoy, K. N. (1994) Effects of β-carotene supplementation on lipid peroxidation in humans. Am. J. Nutr. 59: 884-890.
Ames, B. A., Shingenaga, M. K. & Prak, E. M. (1991) Oxyradicals and DNA damage: In: Davies, K. J. A. (ed). Oxidation damage and repair: Chemical Biological and Medical Aspects. Pergamon Press. Elmsford, N. Y. pp.181-187.
Bellamy, M. F., McDowell, I. F., Ramsey, M. W., Brownlee, M., Newcombe, R. G. & Lewis, M. J. (1999) Oral folate enhances endothelial function in hyper-homocysteinaemic subjects. Eur. J. Clin. Invest. 29: 659-662.
Boushey, C.J., Beresford, S.A., Omenn, G.S. & Motulsky, A.G. (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. J. A. M. A. 274: 1049-1057.
Brattstron, L., Linger, A.,Israelaaon, B., Malinow, M. R., Norrving, B., Vpson, B. & Hamfelt, A. (1995) Hyperhomocysteinaemia in stroke: prevalence cause, and relationships to type of stroke and stroke risk factors. Eur. J. Clin. Invest. 22: 214-221.
Brody, T. (1991) Folic acid: In: Mashlin, L. J. (ed). Handbook of vitamins. Marcel Decker, Inc., New york, N. Y. pp. 453-489.
Bunout, D., Garrido, A., Suazo, M., Kauffman, R., Venegas, P., Maza, P., Petermann, M. & Hirsch, S. (2000) Effects of supplementation with folic acid and antioxidant vitamins on homocysteine levels and LDL oxidation in coronary patients. Nutr. 16: 107-110.
Burton, G. W. & Ingold, K. U. (1989) Vitamin E as an in vitro and vivo antioxidant. Ann. N. Y. Acad. Sci. 570: 7-22.
Burton, G. W. & Ingold, K. U. (1990) Mechanisms of antioxidant action: preventive and chain-breaking antioxidants. In: Miguel, A., Quintanilha, A. T. & Weber, H. (ed). Handbook of free radicals and antioxidants in biomedicine. CRC. Press. Boca. Raton, F. L. pp. 29-43.
Chambers, J. C., McGregor, A., Jean-Marie, J., Obeid, O. A. & Kooner, J. S. (1999) Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy. Circulation 99: 1156-1160.
Chasan-Taber, L., Selhub, J., Rosenberg, I.H., Malinow, M.R., Terry, P., Tishler, P. V., Willett, W., Hennekens, C. H. & Stampfer, M. T. (1996) A prospective study of folate and vitamin B6 and risk of myocardial infarction in US physicians. J. Am. Coll. Nutr. 15: 136-143.
Coelho, C. N. & Klein, N. W. (1990) Methioine and neural tube closure in cultured rat embryos: Morphological and biochemical analyses. Teratology 42: 437-451.
Cohen, G. & Hochstein, P. (1963) Glutathione peroxidase: the primary agent for the elimination of hydrogen peroxide in erythrocytes. Biochemistry 2: 1420-1428.
Corbett, S. W., Stern, J. s. & Keesey, R. (1986) Energy expenditure in rats with diet-induced obesity. Am. J. Clin. Nutr. 44: 173-180.
Daly, L. E., Kirke, P. N., Molloy, A. Weir, D. G. & Scott, J. M. (1995) Folate levels and neutral tube defects, implications for prevention. J. A. M. A. 274: 1698-1702.
Dawson, E. B., Evans, D. R. & Van Hook, J. W. (1998) Amniotic fluids B12 and folate levels associated with neural tube defects. Am. J. Perinatol. 15: 511-514.
Durand, P., Prost, M. & Blache, D. (1996) Pro-thrombtic effects of folic acid deficient diet in rat platelets and macrophage related to elevated homocysteine and decreased n-3 polyunsaturated fatty acid. Atherosclerosis 121: 231-243.
Durand, P., Prost, M. & Blache, D. (1997) Folic acid deficiency enhances oral contraceptive-induced platelet hyperactivity. Arterioscler Thromb Vasc Biol. 17: 1939-1946.
Durand, P., Fortin, L. J., Lussier-Cacan, S., Davignon, J. & Blache, D. (1996) Hyperhomocysteinemia induced by folic acid deficiency and methionine load-applications of a modified HPLC methods. Clin. Chim. Acta. 252: 83-93.
Esterbaucr, H. & Ramos, P. (1995) Chemistry and pathophysiology of oxidation of LDL. Rev. Physiol. Biochem. Pharmacol. 127: 31-64.
Fishwe, A. B. (1998) Intracellular production of oxygen derived free radicals. In: Halliwell, B (ed). Free radicals and tissue injury. Proc. Upjohn. Sympo. F. A. S. E. B. Press, Rockville, Bethesda, M. D. pp. 34-42.
Folch, J., Lees, M. & Stanel, G. S. H. (1957) A simple method for the isolation and purification of total lipids from animal tissue. J. Biol. Chem. 226: 497-509.
Fridovich, I. (1975) Superoxide dismutase. Annu. Rev. Biochem. 44: 147-159.
Gaggi, R. & Gianni, A. M. (1973) The role of homocysteine in the pathogenesis of atheriosclerosis. Proc. First. Congr. Hung. Pharmacol. Soc. 2: 287.
Gate, L., Paul, J., Ba, G. N., Tew, K. D. & Tapiero, H. (1999) Oxidative stress induced pathologies: the role of antioxidants. Biomed. Pharmacother. 53: 169-180.
Ghosal, A. K. & Farber, E. (1993) Choline deficiency, lipotrope deficiency and the development of liver disease including liver cancer. A new perspective. Laboratory Invest. 68: 255-260.
Giles, W. H., Kittner, S. J., Anda, R. F., Croft, J. B. & Casper, M. L. (1995) Serum folate and risk for ischemic stroke. First national health and nutrition examination survey epidemiologic follow-up study. Stroke 26: 1166-1170.
Goldberg, D. M. & Spooner, R. J. (1983) In methods of enzymatic analysis: In: Bergmeten, H. V. (ed). pp: 258-265.
Gospe, S. M. Jr, Gietzen, D. W., Summers, P. J., Lunetta, J. M., Miller, J. W., Selhub, J., Ellis, W. G. & Clifford, A. J. (1995) Behavioral and neurochemical changes in folate-deficient mice. Physiol. Behav. 58: 935-941.
Graham, I. M., Daly, L.E., Refum, H. M., Robinson, K., Brattstrom, L.E. & Ueland, P. M. (1997) Plasma homocysteine as a risk factor for vascular disease: the European Concerted Action Project. J. A. M. A. 277: 1775-1781.
Gutteridge, J. M. C. (1998) Lipid peroxidation: some problems and concepts. In: Halliwell, B(ed). Oxygen radical and tissue injury. Pro. Upjohn. Symposium. R. A. S. E. B. Press, Rockville, Bethesda, M. D. pp.9-19.
Harats, D., Ben-Naim, M., Dabach, Y., Hollander, G., Havivi, E., Stein, O. & Stein, Y. (1990) Effect of vitamin C and E supplementation on susceptibility of plasma lipoprotein to peroxidation induced by acute smoking. Atherosclerosis 85: 47-54.
Henning, S. M., Swendseid, M. E., Ivandic, B. T. & Liao, F. (1997) Vitamin C, E and A and heme oxygenase in rats fed methylfolate-deficient diets. Free. Radic. Biol. Med. 23: 936-942.
Hissin, P. J. & Hilf, R. (1976) A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal. Biochem. 74: 214-226.
Huang, T. C., Chen, C. P., Wefler, V. & Raftery, A. (1961) A stable reagent for the Liebermann-Burchard reaction. Anal. Chem. 33: 1405-1407.
Kazzaz, J. A., Xu, J., Palaia, T. A., Mantell, L., Fein, A. M. & Horowitz, S. (1996) Cellular oxygen toxicity. Oxidant injury wiyhout apoptosis. J. Biol. Chem. 271: 15182-15186.
Kim, Y. I., Miller, J. W., da Costa, K. A., Nadeau, M., Smith, D., Selhub, J., Zeisel, S. H. & Mason, J. B. (1994) Severe folate deficiency causes secondary depletion of choline and phosphocholine in rat liver. J. Nutr. 124: 2197-2203.
Kirke, P. N., Molloy, A. M., Daly, L.E., Burke, D. G. & Soott, J. M. (1993) Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects. Q. J. Med. 86: 703-708.
Lin, B. F., Lin, R.F. Yeh, W. T. & Pan, W. H. (1999) The folate status in Taiwanese population from the NAHSIT 1993-1996. Nutr. Sci. J. 24: 99-117.
Lin, J., Kang, S., Zhou, J. & Wong, W. K. (1989) Homocysteinemia in rats induced by folic acid deficiency. Life Sci. 44: 319-325.
MaCall, M. R. & Frei, B. (1999) Can antioxidant vitamins materially reduce oxidative damage in humans ? Free Radic. Biol. Med. 26: 1034-1053.
Machlin, L. J. (1991) Handbook of vitamins. 2nd ed. pp. 453-490.
Malinow, M. R. (1990) Hyperhomocyst(e)inemia. A common and esily reversible risk factor for occlusive atherosclerosis. Circulation 81: 2004-2006.
Miller, J. W., Nadeau, M. R., Smith, J., Smith, D. & Selhub, J. (1993) Folate-deficiency-induced homocysteinemia in rat: disruption of S-adenosylmethioine’s coordinate regulation of homocysteine metabolism. Biochem. J. 298: 415-419.
Mitton, K. P. & Trevithick, J. R. (1994) High-performance liquid chromatography-electrochemical detection of antioxidants in vertebrate lens: glutathione, tocopherol, and ascorbate. Methods Enzymol. 233: 523-539.
Morrison, H. I., Schaubel, D., Desmeules, M. & Wigle, D.T. (1996) Serum folate and risk of total coronary heart disease. J. A. M. A. 275: 1983-1986.
Nierenberg, D. W. & Nann, S. L. (1992) A method for determining concentrations of retionol, tocopherol, and five carotenoids in human plasma and tissue samples. Am. J. Clin. Nutr. 56: 417-426.
Olszewski, A. J., Szostak, W. B., Bialkowska, M., Rudnicki, S. & McCully, K. S. (1989) Reduction of plasma lipid and homocysteine levels by pyridoxine, folate, cobalamin, choline, riboflavin, and troxerutin in atherosclerosis. Atherosclerosis 75: 1-6.
Paglia, D. E. & Valentine, W. N. (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. 70: 158-169.
Pan, W. H., Chang, Y. H., Chen, J. Y., Wu, S. J., Tzeng, M. S. & Kao, M. D. (1999) Nutrition and health survey in Taiwan (NAHSIT) 1993 ~ 1996: dietary nutrition intake assessed by 24-hour recall. Nutr. Sci. J. 24: 11-39.
Peter, O. & Kwiterovich, M. D. Jr. (2000) The metabolic pathways of high-density lipoprotein, low-density lipoprotein, and triglycerides: a current review. Am. J. Cardiol. 86: 5L-10L.
Pomfret, E. A. da Costa, K. A. & Zeisel, S. H. (1990) Effects of choline deficiency and methotrexate treatment upon rat liver. J. Nutr. Biochem. 1: 533-541.
Regine, P. & Theunissen, S. (1995) Folate metabolism and neural tube defects: a review. European Jouanal of Obstetrics & Gyneclogy and Reproductive Biology. 61: 39-48.
Rimm, E. B., Willett, W. C. & Hu, F. B., Samposon, L., Colditz, G. A., Manson, J. E., Hennekens, C. & Stampfer, M. J. (1998) Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. J. A. M. A 279: 359-364.
Shan, X. O., Aw, T. Y. & Jones, D. P. (1990) Glutathione dependent protection against oxidative injury. Pharmocol. Ther. 47: 61-71.
Smolin, L. A. & Grosvenor, M. B. (2000) Nutrition Science and Applications. 3rd. Saunders College Publishing. Orlando, F. L. pp. 262-266.
Stadtman, E. R. (1992) Protein oxidation and aging. Science 257: 1220-1224.
Stahl, W. & Sies, H. (1997) Antioxidant defense: vitamin E and C and Carotenoids. Diabetes 46: S14-S18.
Stamfer, M. J. & Rimm, E. B. (1996) Folate and cardiovascular disease. Why we need a trial now. J. A. M. A. 275: 1929-1930.
Sundler, R. & Akesson, B. (1975) Regulation of phospholipid biosynthesis in isolated rat hepatocytes. Effect of different substrates. J. Biol. Chem. 250: 3359-3367.
Tatum, V. L., Changchit, C. & Chow, C. K. (1990) Measurement of malondialdehyde by highperformance lipid chromatography with fluorescence detection. Lipids 25: 226-229.
Temple, M. E., Luzier, A. B. & Kazierad, D. J. (2000) Homocysteine as a risk factor for atherosclerosis. Ann. Pharmacother. 34: 57-65.
Thorand, B., Pietrzik, K., Prinz-Langenohl, R., Hages, M. & Holzgreve, W. (1996) Maternal and fetal serum and red blood cell folate and vitamin B12 concentrations in pregnancies affected by neural tube defects. Z. Geburtshilfe. Neonatol. 200: 176-180.
Trimble, K. C., Molloy, A. M., Scott, J. M. & Weir, D. G. (1993) The effect of ethanol on one-carbon metabolism: increased methionine catabolism and lipotrope methyl-group wastage.Hepatology. 18: 984-989.
Tsen, C. C. & Tappel, A. L. (1958) Catalytic oxidation of glutathione and other sulfhydryl compounds by selenite. J. Biol. Chem. 233: 2130-2332.
Ueland, P.M., Refsum, H., Stabler, S. P., Malinow, M. R., Andersson, A. & Allen, A. H. (1993) Total homocysteine in plasma or serum: method and clinical applications applications. Clin. Chem. 39:1764.
Upchurch, G. R., Welch, G. N., Fabian, A. J., Freedman, J. E., Johnson, J. L., Keaney, J. F. Jr. & Loscalzo, J. (1997) Homocyst(e)ine decreases bioavailable nitric oxide by a mechanism involving glutathion peroxidase. J. Boil. Chem. 272: 17012-17017.
Verhaar, M. C., Wever, R. M., Kastelein, J. J., van Dam, T., Koomans, H. A. & Rabelink, T. J. (1998) 5-methyltetrahydrofolate, the active form of folic acid, restores endothelial function in familial hypercholesterolemia. Circulation 97: 237-241.
Vitorica, J., Machado, A. & Satrustegui, J. (1984) Age-dependent variations in peroxide-utilizing enzymes from rat brain mitochondria and cytoplasm. J. Neurochem. 42: 351-356.
Walzem, R. L. & Clifford, A. J. (1988) Folate deficiency in rats fed diets containing free amino acid or intact proteins. J. Nutr. 118: 1089-1096.
Weler, M. W., Shapiro, S. & Mitchell, A. A. (1993) Periconceptional folic acid exposure and risk of occurrent neural tube defects. J. A. M. A. 269: 1257-1261.
Whitney, E. N. & Rolfes, S. R. (1996) Understanding nutrition. 7th ed. St Paul. Minn: West Publishing Co. pp. 361-6.
Williams, R. J., Motteram, J. M., Sharp, C. H. & Gallagher, P. J. (1992) Dietary vitamin E and the attenuation of early lesion development in modified Watanabe rabbits. Atherosclerosis 94: 153-159.
Wills, L. & Mehta, M. M. (1930) Studies in pernicious anemia of pregnancy partⅠpreliminary report. Ind. J. Med. Res. 17: 777-792.
Wong, S. H., Knight, J. A., Hopfer, S. M., Zaharia, O., Leach, C. N. Jr. & Sunderman, F. Jr. (1987) Lipoperoxides in plasma as measured by liquild-chromatographic separation of malondialdehyde-thiobarbituric acid adduct. Clin. Chem. 33: 214-220.
Yaqoob,P., Sherrington, E. J, Jeffery, N. M., Sanderson, P., Harvey, D. J., Newsholme, E. A. & Calder, P. C. (1995) Comparison of the effects of a range of dietary lipids upon serum and tissue lipid composition in the rat. Int. J. Biochem. Cell Biol. 27: 297-310.
Yates, J. R., Ferguson-Smith, M. A., Shenkin, A., Guzman-Rodriguez, R., White. M. & Clarke, B. J. (1987) Is disordered folate metabolism the basis for the genetic predisposition to neural tube defects ? Clin. Genet. 31: 279-287.