臺灣博碩士論文加值系統

本研究目的是評估海巴戟天葉乙醇萃取物能否有效保護大白鼠體內血液與肝臟免於環磷醯胺（cyclophosphamide）的氧化性傷害。80 隻雄性大白鼠（Sprague-Dawley）隨機分成八組，並餵食AIN-76 動物飼料30天；其中一組大白鼠僅於實驗第15天腹腔注射磷酸鹽緩衝液，當作是控制組（C），而每天攝取每公斤體重0.2克海巴戟天葉 95% 乙醇萃取物（LE95） 的大白鼠為 LE1 組，其餘各組大白鼠分別於實驗第 15 天進行腹腔注射環磷醯胺，並每天攝食每公斤體重0.2克海巴戟天葉 50% 乙醇萃取物（CPLE50 組）、每天攝食 0克 LE95（CP組）、0.2克LE95（CPLE1組）、0.4克LE95（CPLE2組）、1克 LE95（CPLE5組），以及0.2克水飛薊（CPSL組）。實驗於第 30 天結束，並以乙醚麻醉且犧牲大白鼠，採集大白鼠腹腔動脈血，將分離出的血漿和血球，與肝臟組織分別進行抗氧化酵素活性和抗氧化能力的檢定，並進一步評估大白鼠經環磷醯胺誘發氧化傷害下，LE95對於活體內脂質和蛋白質保護的效果。
首先以C、CP、CPLE1、CPLE50和CPSL 五組進行單因數變異數分析（One-way ANOVA），並以Duncan’s test 做顯著性差異比較，評估攝食海巴戟天葉 50% 乙醇萃取物（LE50）、LE95 與水飛薊（silymarin）之間抗氧化能力的潛能。結果顯示攝食 LE95 或 LE50 對大白鼠遭受環磷醯胺誘發氧化壓力下，明顯優於公認有效的保肝劑水飛薊。此外，LE95 對於大白鼠肝臟和血液的抗氧化作用與保護效果，又比 LE50 所發揮的影響效果較顯著且趨於一致性。
在大白鼠遭受環磷醯胺誘發氧化壓力下，爲進一步探討攝取LE95 的劑量效應與LE95和環磷醯胺間之交互作用，對於大白鼠體內抗氧化作用與保護效果的影響，利用 NEST的實驗設計，以C、CP、LE1、CPLE1、CPLE2和CPLE5 六組進行單因數和多因數變異數分析（multiway ANOVA）進行統計。結果顯示：（1）攝取一倍劑量 LE95 的大白鼠在腹腔注射環磷醯胺 7天後，血球麩胱甘肽過氧化酶（GPx）的活性會上升；而在腹腔注射 15天後，則會提升血球麩胱甘肽還原酶（GRd）的活性；除此之外，還能夠減緩肝臟組織發炎、降低AST 活性並有維持相對肝重的效果。（2）攝取二倍劑量 LE95 的大白鼠在腹腔注射環磷醯胺 7天後，血球麩胱甘肽過氧化酶（GPx）的活性會上升；而在腹腔注射 15天後，則會提升血球觸酶（CAT）和血球超氧歧化酶（SOD）的活性；此外，還能夠降低AST 活性、提升肝臟組織中 NPSH、TSH 含量與增加清除 DPPH 自由基的能力。然而，CPLE2組出現相對脾重增加的特殊現象，可能是藉由增加脾臟細胞增生的速率抵抗該組溶血性貧血的結果。（3）攝取五倍劑量 LE95 的大白鼠能夠降低AST 活性、提升肝臟組織中 NPSH、TSH 含量與增加清除 DPPH 自由基的能力；然而，卻有較高的 MCH 値、加重血漿中蛋白質結構的氧化性傷害和降低遭受氧化壓力 15 天後血球觸酶（CAT）的活性，顯示攝取高劑量的 LE95 有加重氧化壓力，並引發大白鼠體內血液進一步受到氧化傷害的現象。
綜合以上結果顯示海巴戟天葉 95% 乙醇萃取物對於受到氧化壓力的大白鼠，在血液與肝臟上具有一些保護效果；然而，要發揮抗氧化作用和保護效果，與攝食LE95的劑量有關。

The aim of the present study was to evaluate the influence of ethanolic extracts of Noni leaves on the antioxidative properties of the blood and liver of rats exposed to cyclophosphamide. Eighty adult male Sprague-Dawley rats were divided into eight groups randomly and fed with AIN-76 diet for 30 days. One group was injected intraperitoneally with phospahte saline buffer on the fifteenth day and served as the control group（C）. The LE1 group was indicated that the rats received 95% ethanolic extracts of Noni’s leaves（LE95） at a dose of 0.2g/kg body weight per day. The others were fed with 50% ethanolic extracts of Noni’s leaves at a dose of 0.2（CPLE50）, LE95 at a dose of 0 （CP）, 0.2 （CPLE1）, 0.4（CPLE2）, 1（CPLE5）g/kg body weight or fed with silymarin（CPSL）at a dose of 0.2 g/kg body weight per day, and injected intraperitoneally with cyclophosphamide in phospahte saline buffer on the fifteenth day. After thirty days of administration, rats were sacrificed by ether anaesthesia. Blood of rat’s abdominal artery were drawn with an anticoagulant. Red blood cells, plasma and liver tissues were used for antioxidant enzymes or non-enzymatic antioxidants assays. Further study was to prove the 95% ethanolic extracts of Noni leaves（LE95）in the protection ability of lipid peroxidation and oxidative damage of protein caused by cyclophosphamide.
The first statistical analysis was to evaluate the antioxidative potential of the ethanolic extracts of Noni leaves（LE95 and LE50）in comparison with silymarin. The data were analyzed by one-way ANOVA with Duncan’s test for multiple comparisons to determine significance among C, CP, CPLE1, CPLE50, CPSL groups. The results implied that ethanolic extracts of Noni leaves had better antioxidative properties against oxidative stress induced by cyclophosphamide than silymarin which is well known as hepatic protective drug. Furthermore, LE95 appeared the marked and consistent antioxidative protection effects in rat livers and blood system, but not in LE50.
To further examine whether antioxidative protection effects of LE95 were also affected by the doses of LE95 and the interaction of LE95 with cyclophosphamide, a nested experimental design was evaluated. The data were analyzed by one-way and multiway ANOVA among C, CP, LE1, CPLE1, CPLE2, CPLE5 groups. The results indicated as following.（1）The rats received LE95 at a dose of 0.2g/kg body weight per day had higher the glutathione peroxidase activity（GPx） during 7 days and higher the glutathione reductase activity（GRd）during 15 days after cyclophosphamide administration in red blood cells than the other groups. In addition, a decrease of aspartate aminotransferase activity（AST）, normal hepatic tissue biopsy and normal relative liver weight were observed in rats dosed with 0.2g/kg body weight of LE95.（2）The rats received LE95 at a dose of 0.4g/kg body weight per day had higher the GPx during 7 days and higher the catalase（CAT）and superoxide dismutase activity（SOD）during 15 days after cyclophosphamide administration in red blood cells. In addition, a decrease of AST, increase hepatic NPSH, TSH contents and increase scavenging ability of DPPH in rat liver were observed. However, the dramatic increase of relative spleen weight in CPLE2 group. The result indicated that the rats received LE95 at a dose of 0.4g/kg body weight may act against hemolytic anemia by enhancement of the splenocyte proliferation rate.（3）The rats received LE95 at a dose of 1g/kg body weight per day could decrease AST, increase hepatic NPSH, TSH contents and increase scavenging ability of DPPH in rat liver. However, higher MCH value, higher carbonyl group’s content of plasma, and lower CAT during 15 days after cyclophosphamide administration in red blood cells were observed. These results implied that higher dosage of LE95 may appear aggravating oxidative damage in blood system of rats.
In conclusion, our results suggest that LE95 had some protection effects on blood and liver in rats from oxidative stress. However, the effectiveness of LE95 relates to the dose of usage.

中文摘要 ………………………………………………………………Ⅰ
英文摘要 ………………………………………………………………Ⅳ
謝誌 ……………………………………………………………………Ⅶ
目錄 ……………………………………………………………………Ⅸ
表目錄 ……………………………………………………………ⅩⅣ
圖目錄 ………………………………………………………………ⅩⅦ
縮寫表 ………………………………………………………………ⅩⅧ
第一章 前言……………………………………………………………1
第二章 文獻整理………………………………………………………3
一、自由基相關文獻回顧……………………………………………3
(一) 生物體內氧化壓力的形成………………………………………3
1. 氧化壓力的形成……………………………………………………3
2. 自由基或活性氧的定義及反應型式………………………………4
3. 自由基或活性氧的種類……………………………………………5
4. 自由基或活性氧產生的途徑………………………………………8
5. 自由基或活性氧對生物體分子的傷害……………………………10
(二) 生物體內抗氧化壓力防禦系……………………………………11
1. 抗氧化酵素系………………………………………………………12
2. 非酵素性抗氧化系統……………………………………………15
二、海巴戟天相關文獻回顧 ………………………………………23
(一) 海巴戟天的簡介 ………………………………………………23
(二) 海巴戟天的主要成分 …………………………………………25
(三) 海巴戟天的生物活性 …………………………………………25
三、實驗架構 ………………………………………………………27
(一) 動物實驗架構 …………………………………………………27
(二) 海巴戟天葉乙醇萃取物對大白鼠血液抗氧化弁鄋熊��?……28
(三) 海巴戟天葉乙醇萃取物對大白鼠肝臟抗氧化弁鄋熊��?……28
第三章 材料與方法……………………………………………………29
一、實驗材料…………………………………………………………29
(一) 藥品與溶劑………………………………………………………29
(二) 動物品系及飼料…………………………………………………30
二、儀器設備…………………………………………………………31
三、實驗設計及分組………………………………………………31
(一) 海巴戟天葉乙醇萃取物的製備 ………………………………31
(二) 動物飼料的組成及配製 ………………………………………32
(三) 動物飼養 ………………………………………………………32
(四) 動物實驗流程 …………………………………………………33
四、實驗分析項目 …………………………………………………33
(一) 血液與器官的處理 ……………………………………………33
(二) 生化檢驗的分析 ………………………………………………34
(三) 抗氧化酵素活性的測定 ………………………………………34
1. 血液和肝臟超氧歧化酶分析……………………………………34
2. 血液和肝臟葡萄糖六磷酸去氫酶測定…………………………36
3. 血液和肝臟過氧化氫酶測定……………………………………37
4. 血液和肝臟麩胱甘肽過氧化酶測定……………………………37
5. 血液和肝臟麩胱甘肽還原酶測定………………………………38
(四) 抗氧化活性的測定 ……………………………………………38
1. 總抗氧化能力測定………………………………………………38
2. 還原力測定………………………………………………………38
3. 清除 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH•)能力測定 …39
4. 脂質過氧化測定…………………………………………………40
5. 蛋白質羰基含量測定……………………………………………41
(五) 抗氧化物含量的測定 …………………………………………42
1. 血液和肝臟麩胱甘肽的測定……………………………………43
2. 血漿中尿酸和白蛋白含量分析…………………………………43
(六) 肝臟組織切片 …………………………………………………44
(七) 統計分析 ………………………………………………………44
第四章 結果與討論……………………………………………………46
第一部份：海巴戟天葉 95%、50% 乙醇萃取物與水飛薊對大白鼠遭受環磷醯胺氧化壓力的影響評估 ……………………………………46
(一) 大白鼠的體重、食物攝取量及餵食效率………………………46
(二) 大白鼠臟器重量變化……………………………………………46
(三) 大白鼠血液與臟器生化檢驗……………………………………47
(四) 大白鼠血球抗氧化酵素………………………………………50
(五) 大白鼠肝臟抗氧化酵素…………………………………………52
(六) 大白鼠血液抗氧化能力…………………………………………53
(七) 大白鼠肝臟抗氧化能力…………………………………………57
(八) 綜合討論…………………………………………………………58
第二部份：攝食海巴戟天葉 95% 乙醇萃取物和不同劑量對大白鼠遭受環磷醯胺氧化壓力的影響評估 ……………………………………61
(一) 大白鼠的體重、食物攝取量及餵食效率………………………61
(二) 大白鼠臟器重量變化……………………………………………61
(三) 大白鼠血液與臟器生化檢驗……………………………………62
(四) 大白鼠血球抗氧化酵素………………………………………65
(五) 大白鼠肝臟抗氧化酵素…………………………………………67
(六) 大白鼠血液抗氧化能力…………………………………………68
(七) 大白鼠肝臟抗氧化能力…………………………………………71
(八) 綜合討論…………………………………………………………73
第五章 總結論…………………………………………………………76
第六章 參考文獻………………………………………………………77

1. Halliwell B. and Gutteridce JMC, Free radical in biologv and medicine, 2nd ed., Oxford: Clarendon Press; 1989.
2. Halliwell B, Oxidative stress, nutrition and health. Experimental strategies for optimization of nutritional antioxidant intake in humans, Free Radical Research, 1996;25:55-74.
3. Halliwell B. and Gutteridge JMC, Antioxidant defense. Free Radicals in Biology and Medicine. pp. 105-245. Oxford University press Inc., New York. 1998.
4. McLaveu DS, Dietary antioxidants and disease. Med Digest 1996;14: 5-10.
5. Marx JL, Oxygen free radicals linked to many disease. Science 1987;235:529-531.
6. Gutteridge JMC. and Halliwell B, Antioxidants in nutrition health and disease, 1th edition, Oxford: Oxford University Press, 1994.
7. 鍾玉玲，海巴戟天葉、莖及果實粗萃取物的抗氧化活性之比較。私立嘉南藥理科技大學生物科技研究所碩士論文，2004。
8. Cacciuttolo MA. Trinh L. Lumpkin JA, Hyperoxia induces DNA damage in mammalian cells. Free Rad. Biol. Med., 1993;14:267-276.
9. Hyslop PA. Hinshaw DB. Halsy WA, Mechanisms of oxidant-mediated injury. J Biol Chem 1988;263:1665-1675.
10. Sies H, Oxidative stress. Oxidants and antioxidants. Academic Press, London. 1991.
11. Jacob RA, Nutrition, health and antioxidants. INFORM 1994;5:1271-1275.
12. Olanow CW, A radical hypothesis for neurodegeneration. Trends Neurosci 1993;16:439-444.
13. Halliwell B. Murcia MA. Chirico S. Aruoma OI, Free radicals and antioxidants in food and in vivo: What they do and how to work. Crit Rev. Food Sci. Nutr., 1995;35:7-20.
14. Kehrer JP, Mechanisms and effect of lipid peroxidation. Crit. Rev. Toxicol., 1993;23:21-48.
15. Lander HM, An essential role for free radicals and derived species in signal transduction. FASEB J., 1997;11:118-124.
16. 郭靜娟，薏苡籽實之抗氧化成分及其抑制自由基傷害之研究。國立台灣大學食品科技研究所博士論文，2001。
17. Diplock AT. Charleux JL. Crozier-Willi G. et al. Functional food science and defense against reactive oxidative species. British J. Nutr., 1998;80:S77-S112.
18. Young TA. Cunningham CC. Bailey SM, Reactive oxygen species production by the mitochondrial respiratory chain in isolated rat hepatocytes and liver mitochondria: studies using myxothiazol. Archives of Biochem. Biophy., 2002;405:65-72.
19. Weisiger RA. Fridovich I, Superoxide dismutase. J Biol Chem, 1973;248:3582-3592.
20. Anthony WS. Arie A, The biochemical basis of the NADPH oxidase of phagocytes. TIBS., 1993;18:43-47.
21. Guerciolini R. Szumlanski C. Weinshiboum RM, Human liver xanthine oxidase: nature and extent of individual variation. Clin. Pharmzcol. Ther., 1991;50:663-672.
22. James LG. Sareen SG, Advanced nutrition and human metabolism. 3rd ed., Wadsworth Press, USA, 2000.
23. Ünlü A. Sucu N. Tamer L. et al. Effects of Daflon on oxidative stress induced by hindlimb ischemia/reperfusion. Pharmacological Res., 1998;48:11–15.
24. Gutteridge J. Halliwell B, The measurement and mechanism of lipid peroxidation in biological systems. Trends Biochem. Sci., 1990;15:129-135.
25. Marnett LJ. Burcham PC, Endogeneous DNA adducts: potential and paradox. Chem. Res. Toxicol., 1993;6:771-785.
26. Matés JM. Pérez-Gómez C. Castro I, Antioxidant enzymes and human diseases. Clin. Biochem. 1999;32:595-603.
27. Marklund S, Distribution of Cu/Zn supeoxide dismutase and Mn supeoxide dismutase in human tissue and extracellular fluid. Acta Physiol. Scand. Suppl. 1980;492:19-23..
28. Stralin P. and Marklund SL, Effects of oxidative stress on expression of extracellular superoxide dismutase, CuZn-superoxide dismutase and Mn-superoxide dismutase in human dermal fibroblasts. Biochem J 1994;298:347-52.
29. MacMillan-Crow LA. Crow J P. Thompson J A, Peroxynitrite-mediated inactivation of manganese superoxide dismutase involves nitration and oxidation of critical tyrosine residues. Biochem. 1998;37:1613-1622.
30. Haan JD. Bladier C. Griffiths P, Mice with a homozygous null mutation for the most abundant glutathione peroxidase, Gpx1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide. J. Biol. Chem.273: 22528-22536.
31. Turrens JF. Crapo JD. Freeman BA, Protection against oxygen toxicity by intravenous injection of liposome-entrapped catalase and superoxide dismutase. J. Clin. Invest. 1984;73: 87-95.
32. Young IS. Woodside JV, Antioxidants in health and disease. J Clin Pathol 2001;54: 176-186.
33. Hatheill JR. Till GO. Ward PA, Mechanisms of oxidant-induced changes in erythrocytes. Agents And Actions 1991;32:351-358.
34. Jialal I. Vega GL. Grundy SM, Physiologic levels of ascorbate inhibit the oxdative modification of low density lipoprotein. Atherosclerosis 1990;82:185-191.
35. Levine M. Rumsey S. Daruwala R, Criteria and recommendations for vitamin C intake. JAMA 1999;281: 1415-1423.
36. Sastre J. Pallardo FV. Pla R, Aging of the liver: age-associated mitochondrial damage in intact hepatocytes. Hepatology 1996;24: 1199-1205.
37. Hanna E. Sherman AC, Quality-of-life issues in head and neck cancer.Current Oncology Reports 1999;1: 124-128.
38. Lass A. Sohal RS, Electron transport-linked ubiquinone-dependent recycling of mitochondrial membranes. Arch Biochem Biophys 1998;352: 229-236.
39. Esterbauer H. Dieber-Rotheneder M, Role of vitamin E preventing the oxidation of low-density lipoprotein. Am J Clin Nutr 1991;53:314s-321s.
40. Burton GW. Ingold UK, β-carotene: an unusual type of lipid antioxidant. Sci 1984;224: 569-573.
41. Gottlieb K. Zarling EJ. Mobarhan S, Beta-carotene decreases markers of lipid peroxidation in healthy volunteers.Nutr Cancer 1993;19: 207-212.
42. Keys SA. Zimmerman WF, Antioxidant activity of retinal, glutathione,and taurine in bovine photoreceptor cell membranes. Exp Eye Res 1999;68:693-702.
43. Ames BN. Cathcart R. Schwiers E. Hochstein P, Uric acid provides and antioxidant defense in humans against oxidant and radical-caused aging and cancer. A hypothesis. Proc Natl Acad Sci USA 1981;78: 6858-6862.
44. Krinsky NI, Machenism of action of biological antioxidants. Proc Soc Exp Med 1992;200: 248-254.
45. Davies KJA. Sevaian A. Muakkassah-Kelly SF. Hochstein P, Uric acid-iron ion complexes. A new aspect of the antioxidant functions of uric acid. Biochem J 1986;235: 747-754.
46. Sevanian A. Davies KJA. Hochstein P, Serum urate as an antioxidant for ascorbic acid. Am J Clin Nutr 1991;54: 1129s-1134s.
47. Ratty AK. Das NP, Effects of flavonoids on nonenzymic lipid peroxidation: Structure activity relationship. Biochem Med Metabol Biol 1988;39:69-79.
48. Hertog MGL. Feskens EJM. Hollman PCH, Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study.Lancet 1993;342:1007-1011.
49. Frankel EN. Kanner J. German JB, Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet 1993;341:454-457.
50. Benito S. Lopez D. Saiz MP, A flavonoid-rich diet increases nitric oxide production in rat aorta. British J Pharmacol 2002;135:910-916.
51. Hollman PCH. Hertog MGL. Katan MB, Analysis and health effects of flavonoids.Food Chem 1996;57: 43-46.
52. Quaglia MG. Bossu E. Donati E. Mazzati G. Brandt A, Determination of high performance liquid chromatography and capillary electrophoresis. Pharma. and Biomed. Analy. 1999;19: 435-442.
53. Kuz’menko DI. Laptev BI, Reserve of serum lipids for peroxidation during oxidative stress in rats. Voprosy Meditisinskoi Khimi 1999;45: 47-52.
54. Letteron P. Labbe G. Degott C, Mechanism for the protective effects of silymarin against carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice. Biochem. Pharma. 1990;39:2027-2034.
55. Boigk G. Stroedter L. Herbst H, Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats. Hepato. 1997;26: 643-649.
56. 蕭培根。中國本草圖錄。商務印書館有限公司。香港。1988-1997。
57. Mian-Y. et al, Morinda citrifolia (Noni) : A literature review and recent advances in Noni research. Acta. Pharmacologica Sinica., 2002;23(12):1127-1141,.
58. Levand O. Larson HO, Some chemical cons tituents of Morinda citrifolia. Planta Med., 1979;36:186-7.
59. Heinicke R, The pharmacologically active ingredient of Noni. Bulletin of the National Tropical Botanical Garden, 1985.
60. Sang S. Cheng X. Zhu N. et al. Flavonol glycosides and novel iridoid glycoside from the leaves of Morinda citrifolia. J. Agric. & Food Chem., 2001;49(9): 4478-81.
61. Zin ZM. Abdul-Hamid A. Osman A, Antioxidative activity of extracts from Mengkudu (Morinda citrifolia L.) root, fruit and leaf. Food Chemistry, 2002;78:227 –231.
62. McCord J M. Fridovich I, An enzyme function for erythrocuprein (hemocuprein). J. Biol. Chem. 1969;244:6049-6055.
63. McCord JM, The evolution of free radicals and oxidative stress. Am. J. Med. 2000;108(8): 652-659.
64. Cohen G. Dembiec D. Marcus J, Measurement of catalase in tissue extracts. Anal. Biochem. 1970;34:30-38.
65. Lawerence RA. Burk RF, Glutathione peroxidase activity in selenium-deficient rats liver. Biochem. Biophys. Res. Commun. 1976;71:952-958.
66. Bellomo G. Mirabelli F. Dimonte D, Formation and reduction of glutathione-mixed disulides during oxidative stress. Biochem. Pharmacol. 1987;36:1313-1320.
67. Re R. Pellegrini N. Proteggente A. et al, Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biol Med; 1999;26:1231–1237.
68. Oyaizu M, Antioxidative activity of browning products of glucosamine fractionated by organic solvent and thin-layer chromatography. Nippon Shokuhin Kogyo Gakkaishi. 1986;35:771-775.
69. Shimada K. Fujikawa K. Yahara K. Nakamura T, Antioxidative properties of xanthan on the autoxidation of soybean oil in cyclodextrin emulsion. J. Agric. Food Chem. 1992;40:945-948.
70. Buege AJ. Aust SD, Microsomal lipid peroxidation. Methods Enzmol. 1978;52:302-310.
71. Reznick AZ. Packer L, Methods in Enzymology. 1994;233:357-363.
72. Hu ML, Measurement of plasma protein thiopls and GSH. Methods Enzymol. 1994;233:380-385.
73. Hissin PJ. Hilf R, A fluorometric method for determination of oxidized and reduced glutathione in tissues. Analytical Biochem. 1976;74:214–226.
74. De la Iglesia F. Sturgess JM. Feuer G, New approaches for assessment of hepatotoxicity by means of quantitative functional-morphological interrelationship in toxicity of liver. Eds. G.L. Plaa and W. R. Hewitt. New York: Raven Press. Clarendon Press.Oxford. P. 1982; 23-28.
75. Velmurugan B. Bhuvaneswari V. Balasenthil S. Nagini S,Lycopene, an antioxidant carotenoid modulates glutathione-dependent hepatic biotransformation enzymes during experimental gastric carcinogenesis. Nutri. Res. 2001;21: 1117-1124.
76. Kasahara K. Nishikawa A. Furukawa F, A chronic toxicity study of josamycin in F344 rats. Food. Chem. Toxicol. 2002;40 (7): 1017-1022.
77. Anna S. Elzbieta S. Marek M, Effects of amifostine on liver oxidative stress caused by cyclophosphamide administration to rats.2002
78. Potter DW. Tran TB, Apparent rates of glutathione turnover in rat tissues. Toxicol. Appl. Phaemacol. 1993;81:416-430
79. Drury JA. Nycyk JA. Baines M. Cooke RW, Does total antioxidant status to outcome in very preterm infants? Clin Sci 1998;94: 197-201.
80. MacKinnon KL. Molnar A. Lowe D. Watson ID. Shearer E, Measures of total free radical activity in critically ill patients. Clin Biochem 1999;32: 263-268.
81. Wayner DDM. Burton GW. Ingard KU. Barclay LRC. Locke SJ, The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical trapping antioxidant activity of human blood and plasma. 1987
82. Elhaimeur F. Courderot-Masuyer C. Nicod L, A. Dietary vitamin C supplementation decreases blood pressure in DOCA-salt hypertensive male Sprague-Dawley rats and this is associated with increased liver oxidative stress. Mol. Cell Biochem. 2002;237(1-2): 77- 83.
83. Skrzydlewska E. Roszkowska A. Makiela M. Skrzydlewski Z, The influence of green tea on the activity of proteases and their inhibitors in plasma of rats after ethanol treatment. Rocz. Akad.Med. Bialymst. 2001;46: 240-250.