臺灣博碩士論文加值系統

摘要
香椿含有大量的酚類化合物，可能具有抗氧化之功效，而能降低活性氧物質對生物體的傷害。本研究之目的在探討不同部位之香椿萃取物清除DPPH自由基的效力及對老化促進小鼠(SAMP8)學習記憶能力、抗氧化狀態與精子品質之影響。體外試驗測試香椿葉、根皮及樹皮萃取物清除DPPH自由基之效力。體內試驗則選用3月齡雄性老化促進小鼠，分別餵食1%香椿葉、1%香椿根皮及1%香椿樹皮萃取物進行12週；另以老化正常小鼠(SAMR1)為正對照組。實驗期間記錄體重及攝食量，並進行行為活動量試驗(open field activity test)、單次被動迴避試驗(single-trial passive avoidance test)及主動迴避試驗(active shuttle avoidance test)。實驗後將動物犧牲，取肝臟和腦部海馬迴、紋狀體及皮質檢測其丙二醛(MDA)含量、超氧歧化酶(SOD)、觸酶(CAT)及麩胱光肽過氧化酶(GSH-Px)之活性，並觀察腦部類澱粉蛋白(Aß)堆積情形。此外，評估精子活動力、濃度及畸形率，另進行血液生化值檢查。體外試驗顯示，香椿葉、根皮及樹皮萃取物於濃度0.625mg/ml時，其清除DPPH自由基效力均達80%以上。體內試驗結果發現攝食量、體重及活動量於五組間並無顯著差異。單次被動迴避試驗顯示以香椿葉萃取物組有較佳學習記憶能力；而主動迴避試驗結果則顯示香椿三部位萃取物均較對照組與正對照組有較佳學習記憶能力，但香椿萃取物組間並無顯著差異。另，給予香椿萃取物的三組(葉、根皮及樹皮組)均能顯著較對照組與正對照組降低腦中類澱粉蛋白的堆積與肝臟及腦部丙二醛之含量，但三組間未達顯著差異。餵食香椿萃取物之三組較對照組與正對照組皆能顯著增加其腦部及肝臟之超氧歧化酶、觸酶及麩胱甘肽過氧化酶活性。三組萃取物中以根皮具最佳促進海馬迴及肝臟中超氧歧化酶之活性與肝臟中觸酶活性之功效，葉萃取物組則有最高的紋狀體及皮質超氧歧化酶活性與肝臟中麩胱甘肽過氧化酶之活性；此外樹皮萃取物組則最能有效增加海馬迴，紋狀體及皮質中麩胱甘肽過氧化酶之活性。餵食香椿三部分萃取物皆能顯著增加精子活動力、精子濃度，並能顯著降低其血清中膽固醇與三酸甘油酯之濃度，但三組間無顯著差異。此外，以香椿葉組有最低的血糖值。相關性分析結果則顯示Aß與腦部SOD、CAT與GSH-Px之活性成負性相關，另與腦部MDA含量成顯著正性相關(P<0.01)。綜合以上的結果顯示，飲食中添加香椿葉、根皮及樹皮萃取物皆能有效促進學習記憶能力，降低脂質過氧化物濃度及腦部組織病變，提升抗氧化防禦系統及精子之品質，至於三種不同萃取物所造成影響之可能機轉則有待進一步的探討。


關鍵詞: 香椿、學習記憶能力、類澱粉蛋白、抗氧化狀態、精子品質

Abstract

Toona sinensis Roemor (TS) may decrease the damage of reaction oxygen species (ROS) because contain a lot of polyphenol compounds which have the antioxidant capacity. The purpose of this study was to examine the DPPH scavenging ability of different parts of TS extracts, and also evaluated the effects on the learning and memory ability, antioxidant status and sperm quality in senescence-accelerated-prone mice (SAMP8). In vitro experiment, the antioxidant capacity of Toona sinensis Roemor leave (TSL), Toona sinensis Roemor root (TSR) and Toona sinensis Roemor bark (TSB) extracts were evaluated by the DPPH radical scavenging test. In vivo experiment, 3-month-old male SAMP8 mice were fed with four different diets for 12 weeks: casein diet group (the control group), casein diet supplemented with 1% TSL, 1% TSR and 1% TSB extracts. Senescence-accelerated-resistant mice (SAMR1) was used for the normal control group and fed with casein diet. Body weight, food intake, open field activity test, single-trial passive avoidance and active shuttle avoidance test were performed. The malondiadehyde (MDA) concentration, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities of liver, hippocampus, striatum and cortex, and the ß-amyloid protein (Aß) deposition of brain were examined after sacarificed. The motility, concentration and abnormality of spermatozoa, and serum biological values were also evaluated. The results of vitro study showed that the DPPH scavenging ability of different TS extracts were over 80% in the concentration of 0.625 mg/ml. In vivo study, the results showed that were no significant differences in the food intake, body weight and locomotion among five groups. The mice fed with TSL extracts had significantly better single-trial passive avoidance results, while three TS diet groups showed better active shuttle avoidance results than the control and normal control groups but no differences were found among three TS diet groups. The Aß deposition of brain and the MDA concentration of liver and brain in three TS extracts groups were significantly lower than the control and normal control groups, whereas no differences were found among three TS diet groups. The SOD, CAT and GSH-Px activity of the brain and liver in the TS extracts groups were significantly higher than the control and normal control groups. It was noted that the TSR diet group had the best SOD activity in the hippocampus and liver, and the best CAT activity in liver; the TSL extract group showed higher SOD activity in striatum and cortex, and GSH-Px activity in liver; and the TSB extracts group had the best GSH-Px activity in the hippocampus, striatum and cortex. The motility and concentration of spermatozoa in mice fed with three TS extracts were significantly higher than the control and normal control groups. The serum triglyceride and total cholesterol concentration of TS extracts groups were significantly lower than the control group but no differences were found among three TS diet groups. The mice fed with TSL extracts were found to have the lowest serum glucose concentration. Pearson correlation analysis showed that the ß-amyloid protein deposition were negatively associated with the SOD, CAT and GSH-Px activity of brain, and also significantly positively associated with the MDA concentration of brain (p<0.01). In summary, we conclude that the supplements of TSL, TSR and TSB extracts could improve the learning and memory ability, reduce the lipid peroxidation and brain pathological changes, and also promote the antioxidative defense system and sperm quality. However, the mechanisms of the effects of different TS extracts are still unknown and need further study.

Keywords: Toona sinensis Roemor, learning and memory, ß-amyloid protein, antioxidative status, sperm quality

目錄
頁次
中文摘要………………………………………………………….........................I
英文摘要………………………………………………………………...................III
目錄…………………………………………………………………….....................V
表目錄………………………………………………………………......................IX
圖目錄………………………………………………………………….....................X

第一章 緒論……………………………………………………………....................1
第二章 文獻回顧………………………………………………………....................4
第一節 香椿………………………………………………………...................4
壹、香椿之介紹……………………………………………...................4
貳、香椿之營養成分及藥理作用…………………………...................4
參、香椿生理功效之研究…………………………………...................6
一、香椿之抗癌作用……………………………………....................6
二、香椿之鎮痛作用……………………………………....................6
三、香椿對血小板凝集作用……………………………....................7
四、香椿之降血糖作用…………………………………....................7
五、香椿對人類精子生理功能之作用…………………....................8
六、香椿對血壓之作用…………………………………....................8
七、香椿之抗氧化作用…………………………………....................8
第二節 自由基及活性氧物質對生物體之探討………………....................10
壹、自由基與活性氧物質之介紹………………………....................10
一、自由基與活性氧物質………………………………...................10
二、自由基與活性氧物質之來源………………………...................10
貳、自由基與活性氧物質對生物體之氧化性傷害……....................12
一、氧化壓力之形成……………………………………...................12
二、氧化傷害之原因……………………………………...................13
三、氧化傷害對生物體之影響…………………………...................13
參、氧化性傷害對疾病及衰老之影響…………………....................16
一、氧化傷害與疾病之相關性…………………………...................16
二、氧化傷害與衰老之相關性…………………………...................16
肆、抗氧化防禦系統與氧化傷害之關係…………………..................22
一、生物體之抗氧化防禦系統…………………………...................22
二、抗氧化劑之作用機制………………………………...................24
第三節 脂質過氧化物產物-丙二醛(MDA)之介紹……………....................26
第四節 超氧歧化酶Superoxide dismutase(SOD)之介紹……….................29
壹、SOD生物學特性及分類…………………………….....................29
貳、SOD之特異性……………………………………….....................30
參、SOD之生理作用…………………………………….....................31
肆、SOD測量之方法…………………………………….....................32
伍、SOD對生物體之影響……………………………….....................32
第五節 觸酶Catalase(CAT)之介紹……………………………...................34
壹、CAT之生理作用…………………………………….....................34
貳、CAT對生物體之影響……………………………….....................35
第六節 麩胱甘肽過氧化酶Glutathione peroxidase (GSH-Px)之介紹...........36
壹、GSH-Px之分類………………………………………....................36
貳、GSH-Px之生理作用…………………………………....................37
參、GSH-Px對生物體之影響……………………………....................38
第七節 類澱粉蛋白質β-amyloid protein (Aβ)之探討………..................40
壹、類澱粉前驅蛋白(Amyloid-ß precursor protein; APP)..............41
貳、類澱粉蛋白(ß-amyloid protein)…………………….................42
第八節 學習記憶之探討………………………………………....................47
壹、學習記憶之簡介……………………………………....................47
一、學習之定義…………………………………………...................47
二、記憶之定義…………………………………………...................48
貳、學習和記憶之類型…………………………………....................48
一、學習的類型…………………………………………...................48
二、記憶的類型…………………………………………...................49
參、學習記憶的實驗模式………………………………....................52
一、古典制約條件反射…………………………………...................52
二、操作性條件反射……………………………………...................52
三、逃避或迴避性條件反射……………………………...................52
四、辨別性學習…………………………………………...................53
肆、學習記憶的生理機制…………………………………..................53
一、學習記憶與神經傳導之關係………………………...................53
二、海馬迴與學習記憶之相關性………………………...................54
三、紋狀體與學習記憶之相關性………………………...................55
第九節 精子品質之探討……………………………………......................57
壹、精子的構造及生成…………………………………....................57
貳、活性氧化物質對精子品質之影響…………………....................58
參、抗氧化劑與精子品質之相關研究…………………....................60
第十節 老化促進小鼠…………………………………………....................64
壹、老化促進小鼠簡介…………………………………...................64
貳、老化促進小鼠開發過程……………………………...................65
參、SAMP8系小鼠………………………………………....................65
肆、SAMR1系小鼠………………………………………....................68
第三章 材料與方法……………………………………………………...................72
第一節 香椿之萃取流程………………………………………....................72
第二節 香椿萃取物清除α,α-diphenyl-ß–picrylhydrazyl(DPPH)自由基效力測定.73
第三節 實驗動物與飼料………………………………………....................74
第四節 實驗流程與方法………………………………………....................76
壹、活動量測試…………………………………………...................78
貳、學習記憶能力測試…………………………………...................78
一、單次被動迴避試驗………………………………....................78
二、主動迴避試驗………………………………………..................79
參、器官均質液之製備及分析流程……………………...................84
肆、氧化狀態之分析……………………………………...................86
一、脂質過氧化物丙二醛之分析……………………....................86
伍、抗氧化狀態之分析…………………………………...................89
一、藥品…………………………………………………..................89
二、儀器設備……………………………………………..................90
三、超氧歧化酶之分析………………………………....................90
四、觸酶之分析………………………………………....................91
五、麩胱甘肽過氧化酶之分析………………………....................92
六、總蛋白質含量之測定……………………………....................94
陸、腦部組織病理切片觀察……………………………...................96
一、儀器設備……………………………………………..................96
二、試藥配製……………………………………………..................96
三、組織切片過程………………………………………..................98
四、ß-類澱粉蛋白染色法……………………………...................100
五、腦部組織病理評估標準…………………………...................102
柒、精子品質之觀測…………………………………....................106
一、儀器設備…………………………………………...................106
二、試藥配製…………………………………………...................106
三、精子活動力之評估………………………………...................106
四、精子濃度之評估…………………………………...................107
五、精子畸形率之評估………………………………...................107
第五節 統計分析…………………………………………….....................108
第四章 結果與討論…………………………………………………....................109
第一節 DPPH自由基效力測定……………………………….....................109
第二節 體重及飼料攝取量……………………………………...................112
第三節 活動量…………………………………………………...................115
第四節 學習與記憶能力………………………………………...................117
壹、單次被動迴避試驗…………………………………..................117
貳、主動迴避試驗………………………………………..................120
第五節 器官重量………………………………………………...................123
第六節 脂質過氧化物丙二醛含量……………………………...................125
第七節 超氧歧化酶之活性……………………………………...................130
第八節 觸酶之活性……………………………………………...................135
第九節 麩胱甘肽過氧化酶之活性……………………………...................140
第十節 腦部ß-類澱粉蛋白沉積………………………………...................145
第十一節 精子品質評估………………………………………...................149
壹、睪丸及副睪重量……………………………………....................149
貳、精子活動力…………………………………………....................151
參、精子濃度……………………………………………....................154
肆、精子畸形率…………………………………………....................157
第十二節 血液生化質分析……………………………………...................159
第十三節 相關性分析...................................................163
第五章 總論…………………………………………………………....................170
第六章 參考文獻……………………………………………………....................173

楊今詳：抗癌中草藥製劑。渡假出版有限公司 pp.165 (1992)
呂鋒洲：抗氧化酵素之介紹。自由基生物學與醫學。1: 1-7 (1993)
行政院主計處內政部：中華民國八十二年老人狀況調查報告 (1994)
黃富順：老化與健康。師大書苑有限公司 pp.7-8 (1995)
丁克祥、邱仲鋒、呂鋒洲：SOD生物與醫學淺論。藝軒圖書出版社。
pp.3-12, 19-32, 204-211 (1996)
張揚全：老年癡呆症。長春月刊 pp.99 (1996)
黃中洋：自由基與自由基排除劑。藥學雜誌 12: 130-138 (1996)
黃鏽萍：核酸混合物對小白鼠學習記憶能力之研究。靜宜大學食品營養系碩士論文 (1996)
陳惠英、顏國欽：自由基、抗氧化防禦與人體健康。中華民國營養學會會誌 23(1): 105-121. (1998)
行政院衛生署：中華民國公共衛生概況。 (1998a)
梁雅芳：核苷與核苷酸混合物對小白鼠記憶能力之影響。靜宜大學食品營養系碩士論文 (1998)
程劍華、李以鑌：抗癌植物藥及其驗方。江西科學出版社pp.608 (1998)
吳淑如：補充綜合抗氧化營養素增強高血脂症抽菸者的抗氧化酵素活性與減少血漿及低密度脂蛋白脂質的過氧化。台北醫學大學保健營養系碩士論文 (1998)。
竹田俊男：SAM。醫學 188(1): 68-74 (1999)
方博正：台灣產生藥之抗氧化及抗皰疹病毒活性資源開發研究。高雄醫學大學天然藥物研究所碩士論文 (2000)
王心聖：何首烏萃取物對小白鼠體內抗氧化酵素活性之影響。靜宜大學食品營養系碩士論文 (2000)
許勝光：90年度保健食品重點研究主題。保健食品跨部會整合推動委員會 pp.200-219. (2001)
王珮憓：椿葉水萃取液在Alloxan所誘發糖尿病鼠中降血糖作用之研究。高雄醫學大學醫學研究所碩士論文 (2001)
曾麗娟、賴俊雄、廖俊旺、王順成：鉛對雄性ICR小鼠睪丸之毒害。中華獸醫誌 27: 113-121 (2001)
楊玉嬌、王珮憓、魏明治、呂勝義、陳彥任、許勝光：香椿之嗎啡樣鎮痛作用。台灣保健食品學會第二屆第二次年會論文摘要p.70 (2002)
查英佑：過氧化氫的暴露影響大鼠精子染色體DNA完整性之研究; 維生素C過氧化氫引起人類精子染色體DNA損傷之研究。高雄第一科技大學環境與安全衛生工所碩士論文 (2002)
賈宜琛：香椿葉部生物活性成份研究。台灣保健食品學會第二屆第二次年會論文摘要 p.71 (2002)
張慧秋、王珮憓、陳彥任、許勝光：椿葉萃取物抗肺癌效果之研究。台灣保健食品學會第二屆第一次年會論文摘要 p.68 (2002)
陳文穎、陳彥任、王珮憓、呂勝義、許勝光：椿葉萃取物對血小板凝集的作用。台灣保健食品學會第二屆第二次年會論文摘要p.70 (2002)
張佩德：Abeta聚合物病理生理特性之研究與銀杏萃取物EGb761對抗Abeta聚合物細胞毒性機轉之探討。國立陽明大學藥理學研究所碩士論文 (2002)
楊馥瑜：香椿對人類精子生理功能之探討。國立成功大學生物學系碩士論文 (2003)
徐沛甄：香椿葉萃取物對老化促進小白鼠學習記憶能力之影響。行政院國家科學委員會補助大專生參與專題研究計劃研究成果報告 (2003)
黃靖容、賈宜琛、許游章、葉哲誠、鍾瞿鴻、楊新玲：香椿萃取物保護對自由基誘導低密度脂蛋白的氧化作用。台灣保健食品學會第三屆第二次年會論文摘要p.47 (2004)
徐沛甄、許勝光、王銘富、廖俊旺、詹吟菁：香椿葉萃取物對老化促進小鼠腦部氧化狀態及老化病理變化之影響。中國農業化學與食品科學期刊 42(3): 200-208 (2004)


Aebi, H. (1983) Catalase. In ”Methods of Enzymatic Analysis” Bergmeyer, H. U. Ed., Weinhein Deerfield beach. FL: VCH. pp. 673-686.
Adams, D. O. & Hanilton, T. A. (1992) Macrophages as destructive cells in host defense. In ”Inflammation: basic principles and clinical correlates” Gallin, J. I., Goldstein, I. M. and Synderman, R. Eds., New York, Raven. pp. 637-662.
Ahamd, S. (1995) Antioxidant mechanisms of enzymes and proteins. In ”Oxidative Stress and Antioxidant Defenses in Biology” Ahamd, S. Chapman & Hall. International Thomaon Publishing Inc. New York. pp. 240-272.
Ahn, H. S., Jeon, T. I., Lee, J. Y., Hwang, S. G., Lim, Y. & Park, D. K. (2002) Antioxidative activity of persimmon and grape seed extract: in vitro and in vivo. Nutr. Res. 22: 1265-1273.
Aitken, R. J. (1995) Free radicals, Lipid peroxidation and sperm function. J. Repord. Fertil. 7: 657-668.
Aitken, R. J. & Clarkson, J. S. (1987) Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J. Reprod. Fertil. 81: 459-469.
Aitken, R. J., Clarkson, J. S., Hargreave, T. B., Irvine, D. S. & Wu, F. C. (1989b) Analysis of the relationship between defective sperm function and the generation of reactive oxygen species in cases of oligozoospermia. J. Androl. 10: 214-220.
Aitken, J. & Fisher, H. (1994) Reactive oxygen species generation and human spermatozoa: the blance of benefit and risk. Bioessays 16: 259-267.
Akiguchi, I., Yagi, H., Ueno, M., Takemura, M., Kitabayashi, T., Seriu, N., Kawamata, S., Nakamura, S., Shimada, A. & Takeda, T. (1994) Age related morphological changes in the brain of senescence-accelerated mouse (SAM-P/8). Elservier Science B. V. All rights reserved. The SAM Model of Senescence. pp. 67-72.
Alessio, H. M. (2000) In ”Handbook of Oxidants and Antioxidants in Exercise” Hanninen, O., Packer, L. & Sen, C. K. Eds., Elsevier, Amsterdam, pp. 115-128.
Almanse, M. S., Del-Rio, L. A. & Sevilla, F. (1994) Characterization of iron-containing superoxide dismutase from a higher plant, citrus limonum. Physiol. Plant 90: 339-347.
Alvarez, J. G., Touchstone, J. C., Blasco, L. & Storey, B.T. (1987) Spontaneous lipid peroxidation and production of hydrogen peroxide and superoxide in human spermatozoa: superoxide dismutase as major enzyme protectant against oxygen toxicity. J. Androl. 8: 338-348.
Ames, B. N. (1990) Endogenous oxidative DNA damage, aging, and cancer. Free Rad. Res. Commun. 7: 121-128.
Ames, B. N., Shigenaga, M. K. & Hagen, T. M. (1993) Oxidants, antioxidants and the degenerative disease of aging. Proc. Natl. Acad. Sci. USA 90: 7915-7922.
Armstrong,J. S., Rajasekaran, M., Chamulitrat, W., Gatti, P., Hellstrom, W. J. & Sikka, S.C. (1999) Characterization of reactive oxygen species induced effects on human spermatozoa movement and energy metabolism. Free Rad. Biol. Med. 26: 869-880.
Aruoma, O. I. (1994) Nutrition and health aspects of free radicals and antioxidant. Food Chem. Toxicol. 32: 1015-1025.
Aruoma, O. I., Halliwell, B. & Williamson, G. (1998) In vitro methods for characterizing potential prooxidant and antioxidant actions of nonnutritive substrance in plant foods. In “Antioxidant Methodology in vivo and in vitro Concepts” Aruoma, O. I. and Cuppett, S. L. Eds., AOCS press, Champaign, Illinois. pp. 173-204.
Auger, J., Kunstmann, J. M., Czyblik, F. & Jouannet, P. (1995) Decline in semen quality among fertile men in Paris during the past 20 years. New Engl. J. Med. 332: 281-285.
Bagchi, D., Hassoun, E. A., Bagchi, M. & Stohs, S. J. (1995) Chromium-induced excretion of urinary lipid metabolites, DNA damage, nitric oxide production, and generation of reactive oxygen species in Sprague-Dawley rats. Comp. Biochem. Physiol. C. Pharmacol. Toxicol. Endocrinol. 110(2): 177-187.
Bartus, R. T., Dean, R. L., Beer, B. & Lippa, A. S. (1982) The cholingergic hypothesis of geriatric memory dysfunction. Science 217: 408-417.
Behl, C., Davis, J., Lesley, R. & Schbert, D. (1992) Vitamin E protects nerve cells from amyloid beta protein toxicity. Biochem. Biophys. Res. Commun. 186: 944-950.
Benzi, G., Pastoris, O., Marzatico, F., Villa, R. F., Dagani, F. & Curti, D. (1992) The mitochondrial electron transfer alteration as a factor involved in the brain aging. Neurobiol. Aging 13: 361-368.
Bernhard, R. (1995) Cytochrome P450: structure, function, and generation of reactive oxygen species. Rev. Physiol. Biochem. Pharmacol. 127: 137-221.
Beyer, W., Imlay, J. & Fridovich, I. (1991) Superoxide dismutase. Prog. Nucl. Acid. Res. Mol. Biol. 40: 221-248.
Borchelt, D. R., Thinakaran, G., Eckman, C. B., Lee, M. k., Davenport, F., Ratovitsky, T., Prada, C. M., Kim, G., Seekins, S. & Yager, D. (1996) Familial Alzheimer’s disease-linked presenilin 1 variants elevate Aβ1-42/1-40 ratio in vitro and in vivo. Neuron 17: 1005-1013.
Bors, W., Heller, W & Michel, C. (1990) Flavonoids as antioxidants: determination of radical scavenging effeciencies . In “Method in Enzymology.” Parker, L & Glazer, A. M. Academic Press. New York. 186: 343-355.
Bradely, T. (1998) Handbook of the aging brain. Chapter 5, pp.83-91.
Bray, R. C., Cockle, S. A., Fielden, E. M., Roberts, P. B., Rotulio, G. & Calabrese, L. (1974) Reduction inactivation of superoxide dismutase by hydrogen peroxide. Biochem. J. 139: 43-48.
Brzezinska-Slebodzinska, E., Slebodzinski, A. B., Pietras, B &Wieczorek, G. (1995) Antioxidant effect of Vitamin E and glutathione on lipid peroxidation in boar semen plasma. Biol. Trace Elem. Res. 47: 69-74.
Buell, S. J. & Coleman, P. D. (1979) Dendritic growth in the aged human brain and failure of growth in senile dementia. Science 206: 854-855.
Butterfield, D. A. & Lauderback, C. M. (2002) Lipid peroxidation and protein oxidation in Alzheimer’s disease brain: potential causes and consequences involving amyloid ß-peptide-associated free radical oxidative stress. Free Rad. Biol. Med. 32(11): 1050-1060.
Cacciuttolo, M. A., Trinh, L., Lumpkin, J. A. & Rao, G. (1993) Hyperoxia induces DNA damage in mammalian cells. Free Rad. Biol. Med. 14: 267-276.
Campbell, B. A. & Haroutunian, V. (1981) Effects of age on long-term memory: Retention of fixed interval responding. J. Gerontol. 36: 338-341.
Cand, F. & Verdetti, J. (1989) Superoxide dismutase, glutathione peroxide, catalase, and liperoxidation in the major organs of the aging rat. Free Rad. Biol. Med. 7: 59.
Carlsen, E., Giwercman, A., Keiding, N & Skakkebaek, N. E. (1992) Evidence for decreasing quality of semen during past 50 years. B. M. J. 305: 609-613.
Catherine, A., Rice, E., Nicholas, J. Miller & George, P. (1997) Antooxidant properties of phenolic compounds. 2(4): 152-159.
Chance, B., Sies, H. & Boveris, A. (1979) Hydroperoxide metabolism in mammalian organs. Physiol. Rev. 59: 527-605.
Chang, H. C., Hung, W. C., Huang, M. S. & Hsu, H. K. (2002) Extract from the leaves of Toona sinensis roemor exerts potent antiproliferative effect on lung cancer cells. Am. J. Chin. Med. 30(2-3): 307-314.
Chen, H., Pellet, L. J., Andersen, H. J. & Tappel, A. L. (1993) Protection by vitamin E, selenium and ß-carotene against oxidative. Free. Rad. Biol. Med. 14: 473-482.
Chen, R. & Wen, H. (1996) Clinical treatment of male infertility with sheng jing pill. Int. J. Orient. Med. 21: 144-147.
Cheng, K. C., Cahill, D. S., Kasai, H., Nishimura, S. & Loeb, L.A. (1992) 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes GT and AC substitution. J. Biol. Chem. 267: 166-172.
Chesseman, K. H. & Slater, T. F. (1999) An introduction to free radical biochemistry. Br. Med. Bull. 49: 481-493.
Chiu, N. Y., Technician, & Chang, K. H. (1995) Toona sinensis (A.Juss)
Roem. In the illustrated medicinal plants of Taiwan, SMC publishing Inc. Taiwan ROC. lst : 131-132.
Cook, T. & Gershon, S. (1981) Strategies for the development of an effective treatment of senile dementia. New Canaan, CT: Mark Powley Associates.
Cos, P., Ying, L., Calominc, M., Hu, J. P., Chnanga, K., Poel, B. V., Picters, L., Vliccctinck, A. J & Berglic, D. V.(1998) Structure activity relactionship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. J. Nat. Prot. 61: 71-76.
Cummins, J. M., Jequier, A. M & Kan, R. (1994) Molecular biology of human male infertility: links with aging, mitochondrial genetics, and oxidative stress? Mol. Reprod. Dev. 37: 345-362.
De Lamirande, E. & Gagnon, C. (1992) Reactive oxygen species and human spermatozoa. I. Effects on the motility of intact spermatozoa and on sperm axonemes. J. Androl. 13: 368-378.
Deiezak, J. D. (1986) Preservatives: Antioxidants- The Ultimate Answer to Oxidation. Food Technol. 40(9): 34.


Di-Patre, P. L., Read, S.L. & Cummings, L. L. (1999) Progression of clinical deteration and pathological changes in patients with Alzheimer’s disease evaluated at biopsy and autopsy. Arch. Neur. 56: 1252-1261.
Draper, H. H., Agarwal, S., Nelson, D. E. V., Wee, J. J., Ghoshal, A. K. & Farber, E. (1995) Effects of peroxidative stress and age on the concentration of a deoxyguanosine-malondialdehyde adduct in rat DNA. Lipid 30(10): 959-961.
Donnelly, E. T., Mcclure, N. & Lewis, S. E. M. (1999) The effect of ascorbate and a-tocopherol supplementation in vitro on DNA integrity and hydrogen peroxide-induced DNA damage in human spermatozoa. Mutagenesis 14: 505-511.
Edmonds, J. M. & Staniforth, M. (1998) Toona Sinensis (Meliaceae). Curtis’s Botanical Magazine 15(3): 186-193.
Elaine, R. & Peskind, M. D. (1996) Neurobiology of Alzheimer’s disease. J. Clin. Psychiatry. 57: 5-8.
Ermak, G. & Davies, K. J. (2002) Calcium and oxidative stress: from cell signaling to cell death. Mol. Immunol. 38: 713-721.
Esch, F. S., Keim, P. S. & Beattie, E. C. (1990) Cleavage of amyloid β-peptide during conservative processing of its precursor. Science 248: 1122-1124.
Esfandiari, N., Saleh, R. A., Blaut, A. P., Sharma, R. K., Nelson, D. R., Thomas, A. J. Jr., Falcone, T. & Agarwal, A. (2002) Effects of temperature on sperm motion characteristics and reactive oxygen species. Int. J. Fertil. Med. 47: 227-233.
Evenson, D. P., Darzynkiewicz, Z. & Melamed, M. R. (1980) Relation of Mammalian Sperm Chromatin Heterogeneity to Fertility. Science 210: 1131-1133.
Fagan, J. M., Sleczke, B. G. & Sohar, I. (1999) Quantitation of oxidative damage to tissue proteins. IJBCB. 31: 751-757.

Festing, M. F. W. (1993) Origins and characteristics of inbred strain of mice. Mouse Genomes 91: 471-472.
Fischhof, P. K., Bernhaut, A. & Friedmann, A. (1993) Senile Dementia and Calcium Channel Blockers : A review. Drugs of Today 29: 57.
Flood, J. F., Farr, S. A., Kaiser, F. E. & Morley, J. E. (1995) Age-related impairment in learning but not memory in SAMP8 female mice. Pharmacol. Biochem. Behav. 50: 661-664.
Flood, J. F. & Morley, J. E. (1990) Pharmacological enhancement of long-term memory retention in old mice. J. Gerontol. Biol. Sci. 45: 101-104.
Flood, J. F. & Morley, J. E. (1992) Early onset of age-related impairment of aversive and appetitive learning in the SAM-P/8 mouse. J. Gerontol. 47: B52-B59.
Flood, J. F. & Morley, J. E. (1993) Age-related changes in foodshock avoidance acquisition and retention in senescence accelerated mouse (SAM). Neurobiol. Aging 14: 153-157.
Flood, J. F. & Morley, J. E. (1998) Learning and memory in the SAMP8 mouse. Neurosci. Biobehav. Rev. 22(1): 1-20.
Floyd, R. A. (1981) Free-radical events in chemical and biochemical reactions involving carcinogenic arylamines. Radiation Res. 86: 243-263.
Forloni, F., Chiesa, R. & Smiroldo, S. (1993) Apoptosis mediated neurotoxicity induced by chronic application of beta amyloid fragment. Neuroreport 4: 523-526.
Fraga, C. G., Motchnik, P. A., Shigenaga, M. K., Helbock, H. J., Jacob, R. A. & Ames, B. N. (1991) Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc. Natl. Acad. Sci. USA 88: 11003-11006.
Frankel, E. N. (1991) Recent advances in lipid oxidation. J. Sci. Food Agric. 54: 495-511.

Fridovich, I. (1975) Superoxide dismutase. Annu. Rev. Biochem. 44: 147-159.
Fridovich, I. (1986) Biological effects of the superoxide radical. Arch. Biochem. Biophy. 247: 1-11.
Fridovich, I. (1988) Superoxide radical: an endogenous toxicant. Annu. Rev. Pharmacol. Toxicol. 23: 239-257.
Games, D., Adams, D. & Alessandrini, R. (1995) Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature 373: 523-527.
Glenner, G. G. & Wong, C. W. (1984) Alzheimer’s disease: Initial report
of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 120: 885-890.
Griveau, J. F. & Le Lannou, D. (1997) Reactive oxygen species and spermatozoa: physiology and pathology. Int. J. Androl. 20: 61-69.
Grundke-Iqbal, I., Iqbal, K., Quinlan, M., Zaidi, M. S. & Wisniewski, H. M. (1986) Microtubule-associated protein tau: a component of Alzheimer paired helical filaments. J. Biol. Chem. 261: 6084-6089.
Golde, T. E., Eckman, C. B. & Younkin, S. G. (2000) Biochemical dectection of Aβ isoforms: implications of pathogenesis diagnosis, and treatment of Alzheimer’s disease. Bioch Biophys Acta. 1502: 172-187.
Gordon, M. H. (1990) The mechanism of antioxidant action in vitro. In ”Food antioxidants”. Hudson, B. J. F., Ed., Elsevier Applied Science: London and New York. pp. 1-18.
Goverde, H. J., Dekker, H. S., Janssen, H. J., Bastiaans, B. A., Rolland, R. & Zielhuis, G. A. (1995) Semen quality and frequency of smoking and alcohol consumption-an explorative study. Int. J. Fertil. Menopausal. Stud. 40: 135-138.
Gutteridge, J. M. C. (1986) Iron promoters of the Fenton reaction and lipid peroxidation can be released from hemoglobin by peroxides. FEBS. Lett. 201: 291-295.
Haass, C., Schlossmacher, M. G. & Hung, A. Y. (1992a) Amyloid β-peptide is produced by cultured cells during normal metabolism. Nature 359: 322-325.
Halliwell, B. & Chirico, S. (1993) Lipid peroxidation: its mechanism, measurement, and significance. Am. J. Clin. Nutr. 57: 715S-725S.
Halliwell, B. & Gutteridge, J. M. C. (1989) Free radicals, aging and disease. In “Free Radicals in Biology and Medicine” Halliwell, B. and Gutteridge, J. M. C. Eds., Clarendon Press, Oxford. pp. 484-487.
Halliwell, B. & Gutteridge, J. M. C. (1991) Free radical in biology and medicine. In “Free Radicals in Biology and Medicine” Halliwell, B. and Gutteridge, J. M. C. Eds., Clarendon Press, Oxford. pp.105-112, 416-493
Halliwell, B., Gutteridge, J. M. C. & Cross, C. E. (1992) Free radicals, antioxidants and human disease: where are we now? J. Lab. Clin. Med. 119(6): 598-620.
Hardy, J. A. & Higgins, G. A. (1992) Alzheimer’s Disease : The Amyloid Cascade Hypothesis. Science 256: 184.
Harman, D. (1956) Aging: a theory based on free radical and radiation chem. J. Gerontol. 11: 298.
Harman, D. (1972) The biologic clock: the mitochondria? J. Am. Geriatr. Soc. 20(4): 145-147.
Harman, D. (1982) Nutritional implications of the free radical theory of aging. J. Am. Coll. Nutr. 1: 27-34.
Harrison, R. A., Mairet, B. & Miller, N. G. (1993) Flow cytometric studies of bicarbonate-mediated Ca2+ influx in boar sperm populations. Mol. Reprod. 35: 197-208.
Hartwig, A. & Schlepegrell, R. (1995) Induction of oxidative DNA damage by ferric iron in mammalian cells. Carcinogenesis 16: 3009-3013.


Hatheill, J. R., Till, G. O. & Ward. P. A. (1991) Mechanisms of oxidant-induced changes in erythrocytes. Agents actions. 32: 351-358.
Hazelton, G. A. & Lang, C. A. (1985) Glutathione peroxide and reductase activities in the aging mouse. Mech. Ageing Dev. 29: 71.
Hefti, F. & Mash, D. C. (1989) Localization of nerve growth factor receptors in the normal human brain and in Alzheimer¢s disease. Neurobiol. Aging 10: 75-97.
Hensley, K., Carney, J. M., Mattson, M. P., Aksenova, M., Harris, M., Wu, J. F., Floyd, R. A. & Butterfiled, D. A. (1994) Amodel for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 91(8): 3270-3274.
Higgins, G. A., Koh, S. & Neve. R. L. (1990) Trophic regulation of basal forebrain gene expression in aging and Alzheimer¢s disease. Prog. Brain Res. 86: 239-255.
Hille, R. & Nishino, T. (1995) Xanthine oxidase and Xanthine dehydrogenase. FASEB. J. 9: 995-1003.
Hodgson, E. K. & Fridovich, I. (1975) The interaction of bovine erythrocyte superoxide dismutase with hydrogen peroxide: Inactivation of the enzyme. Biochemistry 14: 5294-5303.
Hosokawa, M. (1994) Grading score system; a method of evaluation of the degree of senescence in senescence-accelerated mouse (SAM). The SAM model of senescence. pp. 23-28.
Hsu, H. Y. (1997) Infertility. Treatment with Chinese herbal preparations based on presenting conformations. Int. J. Orient. Med. 22: 144-147.
Hsu, P. C., Liu, M. Y., Hsu, C. C., Chen L. Y., and Guo Y. L. L., (1998) Effects of vitamin E and/or C on reactive oxygen species-related lead toxicity in the rat sperm. Toxicology 128: 169-179.


Hu, M. L., Chen, Y. K. & Lin, Y. F. (1995) The antioxidant and pro-oxidant activity of some B vitamins and vitamin-like component. Chem. Biol. Interact. 97: 63-73.
Hughes, C. M., Lewis, S. E., McKelvey-Martin, V. J. & Thompson, W. (1998) The effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity. Hum. Reprod. 13: 1240-1247.
Ii, K. (1995) The role of β-amyloid in the development of Alzheimer’s disease. Drugs & Aging 7: 97-109.
Imre, S. & Juhász, E. (1987) The effect of oxidative stress on inbred mice of different ages. Mech. Ageing Dev. 38: 259.
İnal, M. E., Kanbak, G. & Sunal, E. (2001) Antioxidant enzyme activities and malondialdehyde levels related to aging. Clin. Chem. Acta. 305: 75-80.
Ixatsubo, T. (1995) Wisualization of Ab43(43) and Ab40 in senile plaques with end-specific Ab monoclonals: evidence that an initially deposited species is Ab42(43). Neuron 13: 34-53.
Iwasaki, A. & Gagnon, C. (1992) Formation of reactive oxygen species in species in spermatozoa of infertile patients. Fertil. Steril. 57: 409-416.
Izqierdo, I. (1984) Endogenous state dependends on the relation between the neurohumoral and hormonal states present after training and at time of testing. In “Neuro biology of learning and memory” Lyach, G., McGaugh, J. L. & Weinberger, N. M. Eds., The Guilford Press. New York. pp. 330-350.
Jacob, R. A. (1994) Nutrition, health and antioxidants. INFORM. 5: 1271-1275.
Janero, D. R. (1990) Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Rad. Biol. Med. 9(6): 515-540.
Jennifer, M., Edmonds, & Martin, S. (1998) Toona Sinensis. Bentham-Moxon Trust. 186-196.
Jodar, L. & Kaneto, H. (1995) Synaptic Plasticty: stairway to memory. Jap. J. Pharmacol. 68: 359-387.
Johhson-Wood, K., Lee, M., Motter, R., Hu, K., Gordon, G., Barbour, R., Khan, K., Gordon, M., Tan, H., Games, D., Lieberburg, J., Schenk, D., Seubert, P. & McConlogue, L. (1997) Amyloid precursor protein processing and A beta 42 deposition in a transgenic mouse model of Alzheimer disease. Proc. Natl. Acad. Sci. USA 94: 1550-1555.
Kandel, E. R., Kupfermann, I. & Iversen, S. (2000) Principles of Nenral Science. McGraw-Hill companies, New York. pp. 1227-1245.
Kanematus, S. & Asada, K. (1989) CuZn-Superoxide dismutase in rice: occurrence of an active, monomeric enzyme and two types of isozyme in leaf and non-photosynthetic tissues. Plant Cell Physiol. 30: 381-391.
Katoh-Semba, R. & Kato, K. (1994) Age-related changes in levels of the ß-subunit of nerve growth factor in selected regions of the brain: comparison between senescence-accelerated (SAM-P/8) and senescence-resistant (SAM-R/1) mice. Neurosci. Res. 20: 251-256.
Kesner, P. R. (1991) Neurobiological views of memory. In “Learning and Memory” Martinez, L. J. Jr. & Kesner, P. R. Eds., A Biological View, 2nd ed., New York: Academic Press. pp. 499-541.
Kesner, P. R., Bolland, B. L. & Dakis, M. (1993) Memory for spatial location, motor response, and objects: triple dissociation among the hippocampus, caudate nucleus, and extrastriate visual cortex. Exp. Brain Res. 93: 462-470.
Kim, J. G. & Parthasarathy, S. Oxidation and the spermatozoa. Semin. Reprod. Endocrinol. 16: 235-239(1998).
Klaunig, J. E., Xu, Y., Isenberg, J. S., Bachowski, S., Kolaja, K. L., Jiang, J., Stevenson, D. E. Walborg, E. F. Jr. (1998) The role of oxidative stress in chemical carcinogenesis. Environ. Health Perspec. 106 suppl 1. 1: 289-295.
Klebanoff, S. J. (1988) Phagocytic cells: products of oxygen metabolism. In “Inflammation: Basic principles and clinical correlates” Gallin, J. I., Goldstein, I. M. & Synderman, R. Eds., New York. Raven. pp. 391-444.
Kurokawa, T., Asada, S., Nishitani, S. & Hazeki, O. (2001) Age-related changes in manganese superoxide dismutase activity in the cerebral cortex of senescence-accelerated prone and resistant mouse. Neurosci. Latt. 298: 135-138.
Li, D. J. Li, C. J & Zhu, Y. (1995) Treatment of immunological infertility with Chinese medicinal herbs of aiyin jianghuo. Chung. Kuo. Chung. His. I. Chieh. Ho. Tsa. Chih. 15: 3-5.
Liu, J. & Mori, A. (1993) Age-associated changes in superoxide dismutase activity, thiobarbituric acid reactivity, and reduced glutathione level in the brain and liver in senescence accelerated mice (SAM): a comparison with ddY mice. Mech. Aging Dev. 71: 23-30.
Liu, X. D. (1990) Effect of Chinese medicinal herbs on sperm membrane of infertile male. Chung. His. I. Chieh. Ho. Tsa. Chih. 10: 519-521.
Mahmoodi, H., Hadley, M., Chang, Y. X. & Draper, H. H. (1995) Increased formation and degradation of malondialdehyde-modified proteins under conditions of peroxidative stress. Lipids 30: 936-963.
Mann, T., Jones, R. & Sherins, R. (1980) Oxygen damage, lipid peroxidation, and motility of spermatozoa. In “Testicular Development, Struction and Function” Steinberger, A. & Steinberger, E. Eds., Raven Press. New York. USA pp. 497-501.
Marcus, D. L., Thomas, C., Rodriguez, C., Simberkoff, K., Tsai, J. S., Strafaci, J. A. & Freedman, M. L. (1998) Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer’s disease. Exp. Neurol. 150: 40-44.
Marklund, S. & Marklund, G. (1974) Involvenment of superoxide anion radical in autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem. 47: 469-474.
Markowska, A.L., Spangler, E.L. & Ingram, D.K. (1998) Behavioral assessment of the senescence-accelerated mouse (SAMP8 and R1). Physiol. Behav. 64: 15-26.
Marnett, L. J. & Burcham, P. C. (1993) Endogeneous DNA adducts: potential and paradox. Chem. Res. Toxicol. 6: 771-785.
Matsugo, S., Kitagawa, T., Minami, S., Esashi, Y., Oomura, Y., Tokumaru, S. & Kojo, S. (2000) Age-dependent changes in lipid peroxide levels in peripheral organs, but not in brain, in senescence-accelerated mice. Neurosci. Lett. 278: 105-108.
Matsugo, S., Yasui, F. & Sasaki, K. (2004) Analysis of the oxidative stress state in the brain and peripheral organs of senescence-accelerated mouse model. International Congress Series1260: 251-253.
Masaomi, M., Yoshihiro, K., Naoki, Y., Akinobu, N., Takao, M., Yuji, N. & Toshio, T. (1986) Age-releated changes in learning and memory in the senescence-accelerated mice (SAM). Physiol. Behav. 38: 399-406.
McCord, J. M. (1987) Oxygen derived radicals: a link between reperfusion injury and inflammation. Federation Proc. 46: 2402-2406.
McCord, J. M. & Fridovich, I. (1970) Utility of superoxide dismutase in studying radical reactions. Anal. Biochem. 25: 1374-1377.
McDonald, R. J. & White, N. M. (1994) Parallel information processing in the water maze: Evidence for independent memory systems involving dorsal striatum and hippocampus. Behav. Neural biol. 61: 260-270.
McDonald, R. J. & White, N. M. (1993) A triple dissociation of memory systems: Hippocampus, amygdale, and striatum. Behav. Neurosci. 107: 3-22.

Mehlhorn, R. J. & Cole, G. (1985) The free radical theory of aging: a critical review. Adv. Free Rad. Biol. Med. 1: 165.
Melatonin reduces oxidative damage of neural lipids and proteins in senescence-accelerated mouse. Neurobiol. Aging 23: 639-644.
Meyer, A.S. & Isaksen, A. (1995) Application of enzymes as food antioxidants. Trends in Food Sci. & Tech. 6: 300-304.
Miller, R. A. & Britigan, B. E. (1995) The formation and biological significance of phagocyte-derived oxidants. J. Invest. Med. 43: 39-49.
Mills, J. & Reinger, P. B. (1999) Regulation of Amyloid Precursor Protein Cleavage. J. Neurochem. 72: 443-460.
Miyamoto, M., Kiyota, Y., Yamazaki, N., Nagaoka, A., Matsuo, T., Nagawa, Y. & Takeda, T. (1986) Age-related changes in learning and memory in the senescence-accelerated mouse (SAM). Physiol. Behav. 38(3): 399-406.
Morley, J. E. (2002) The SAMP8 mouse: a model of Alzheimer disease? Biogerontology 3: 57-60.
Mori, T., Kawamata, T., Katayama, Y., Maeda, T., Aoyama, N., Kikuchi, T. & Uwahodo, Y. (1998) Antioxidant, OPC-14117, attenuates edema formation, and subsequent tissue damage follwing cortical contusion in rats. Acta. Neurochir. Suppl (Wien). 71: 120-122.
Morris, R. G. M., Garrud, P., Rawlins, J. N. P. & O’keefe, J. (1982) Place navigation impaired in rats with hippocampal lesions. Nature 297: 681-683.
Mortimer,D., Pandya, I. J. & Sawers, R. S. (1986) Relationship between human sperm motility characteristics and sperm penetration into human cervical mucus in vitro. J. Reprod. Fertil. 78: 93-102.
Muñiz, P., Valls, V., Broseta, C. P., Iradi, A., Climent, J. V., Oliva, M. R. & Sáez, G. T. (1995) The role of 8-hydroxy-2’-deoxyguanosine in riflamycin-induced and damage. Free Rad. Biol. Med. 18: 747-755.
Myhre, A. & Tysnes, O. B. (2002) Etiology and genetics of Alzheimer’s disease. Tidsskrift for Den Norske Laegeforening. 122: 50-53.
Nakahara, H., Kanno, T., & Inai, Y., Ustumi, K., Hiramastus, M., Mori, A. & Packer, L. (1998) Mitochondrial dysfunction in the senescence accelerated mouse (SAM). Free Rad. Biol. Med. 24(1): 85-92.
Nakatani, N. (1997) Antioxidants from spices and herbs. In “Natural Antioxidants Chemistry, Health Effects, Applications.” Shahidi, F. Ed., New Foundland, Canada. pp. 64-75.
Namilk, K. D., Mahmood, M. & Sergio, O. (2000) Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Reprod. Biol. 74: 1200-1207.
Neve, R. L., McPhine, D. L. & Chen, Y. (2000) Alzheimer’s disease: a dysfunction of the amyloid precursor protein. Brain Res. 886: 54-66.
Newton, R. K., Ducore, J. M. & Sohal, R. S. (1989) Effect of age on endogenouse DAN single-strand breakage, strand break induction and repair in the adult housefly. Mutat. Res. 219: 113.
Niki, E. (1992) Active oxygens and free radicals in biology. J. Jpn. Oil Chem. Soc. 41: 768-773.
Oehninger, S., Blackmore, P., Mahony, M. & Hodgen, G. (1995) Effects of hydrogen peroxide on human spermatozoa. J. Assist Reprod Genet. 12: 41-47.
Okatani, Y., Wakatsuki, A., Reiter, R. J. & Miyahara, Y. (2002) Melatonin reduces oxidative damage of neural lipids and proteins in senescence-accelerated mouse. Neurobiol. Aging. 23: 639-644.
Olanow, C. W. (1993) A radical hypothesis for neurodegeneration. Trends. Neurosci. 16: 439-444.
Packard, M. G., Hirsh, R. & White, N. M. (1989) Differential effects of fornix and caudate nucleus lesions on two radical maze tasks: Evidence for multiple memory systems. J.Neurosci. 9: 1465-1472.

Packard, M. G. & McGaugh, J. L. (1992) Double dissociation of fornix and caudate nucleus lesions on acquisition of two watwe maze task: Further evidence for multiple memory systems. Behav. Neurosci. 106: 439-446.
Paglia, D. E. & Valentine, W. N. (1967) Studies on the qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. 70: 159-169.
Papa, S. & Skulachev, V.P. (1997) Reactive oxygen species, mitochondria, apoptosis and aging. Mol. Cell. Biochem. 174:305-319.
Park, J. C., Yu, Y. B., Lee, J. H., Choi, J. S. & Ok, K. D. (1996) Phenolic compounds from the Rachis of Cedrela sinensis. Kor. J. Pharmacogn. 27: 219-223.
Park, S. Y., Bok, S. H., Jeon, S.M., Park, Y. B., Lee, S. J., Jeong, T. S. & Choi, M. S. (2002) Effect of rutin and tannic acid supplements on cholesterol metabolism in rats. Nutr. Res. 22: 283-295.
Pearce, J. M., Roberts, A. D. L. & Good, M. (1998) Hippocampal lesions disrupt navigation based on cognitive maps but not heading vectors. Nature 396: 75-77.
Pike, C. J., Walencewicz, A. J., Glabe, C. G. & Cotman, C. W. (1991) In vitro aging of beta-amyloid protein cause peptide aggregation and neurotoxicity. Brain Res. 563: 311-314.
Pollard, H. B., Arispe, N. & Rojas, E. (1995) Ion channel hypothesis for Alzheimer amyloid peptide neurotoxicity. Cell. Mol. Neurobiol. 15(5): 513-526.
Potegal, M. (1971) A note on spatial-motor deficits in patients with Huntington’s disease: a test of a hypotesis. Neurophychology 9: 233-235.
Potts, R. J., Notarianni, L. M. & Jefferies, T. M. (1999) Seminal plasma reduces exogenous oxidative damage to human sperm, determined by the measurement of DNA strand breaks and lipid peroxidation. Mutat. Res. 447: 249-256.
Pryor, W. A. (1994) Free radicals and lipid peroxidation: what they are and how they got the way. In “Nature Antioxidants in Human Health and Disease” Frei, B., Ed., Academic Press: San Diego, CA. pp.1-24.
Ramarathnam, N., Osawa, T., Ochi, H. & Kawakishi, S. (1995) The contribution of plant food antioxidants to human health. Trends Food Sci. Technol. 6: 75-82.
Rao, G., Xia, E. & Richardson, A. (1990) Effect of age on the expression of antioxidant enzymes in male Fischer F344 rats. Mech. Ageing Dev. 53: 49.
Regen, D. (1996) Cupric ion / ascorbate / hydrogen peroxide-induce DNA damage. Free Rad. Biol. Med. 21: 261-273.
Reiss, U. & Gershon, D. (1976) Rat-liver superoxide dismutase. Purification and age-related modifications. Eur. J. Biochem. 63(2): 617-623.
Reiss, U. & Gershon, D. (1976) Comparison of cytoplasmic superoxide dismutase in liver, heart and brain of aging rats and mice. Biochem. Biophys. Res. Commun. 73(2): 255-262.
Richard, F., Thompson, S. & Jeasnon, J. K. (1996) Memory system in the brain and localization of memory. Proc. Natl. Sci. USA 93: 13438-13444.
Rodriguez, M. M. A. & Ruiz, T. A. (1992) Homeostasis between lipid peroxidation and antioxidant enzyme activities in healthy human aging. Mech. Ageing Dev. 66: 213-222.
Roher, A., Wolfe, D., Palutke, M. & Kukuruga, D. (1986) Purifition, ultrastructure, and chemical analyses of Alzheimer’s disease amyloid plaque core protein. Proc. Natl. Acad. Sci. USA 83: 2662-2666.



Rosenzweig, M. R. & Bennet, E. L. (1984) Basic process and modulatory influences. In ”Neurobiology of learning and memory” Lyach, G., McGaugh, J. L. & Weinberger, N. M. Eds., The Guilford Press. New York. pp. 263-288.
Saleh, R. A., Agarwal, A., Sharma, R. K., Nelson, D. R. & Thomas, A. J. Jr. (2002) Effect of cigarette smoking on levels of seminal oxidative stress in infertile men: a prospective study. Fertil. Steril. 78: 491-499.
Sato, E., Oda, N., Ozaki, N., Hashimoto, S., Kurokawa, T. ＆ Ishibashi, S. (1996) Early and transient increase in oxidative stress in the cerebral cortex of senescence-accelerated mouse. Mech. Ageing Dev. 86: 105-114.
Saul, R. L. & Ames, B. N. (1986) Background levels of DNA damage in the population. Basic Life Sci. 38: 529-535.
Selkoe, D. J. (1993) Physiological production of the beta-amyloid protein and the mechanism of Alzheimer’s disease. Trends Neurosci. 16: 403-409.
Selkoe, D. J. (1994) Alzheimer’s disease: a central ole for amyloid. J. Neuropathol. Exp. Neurol. 53: 438-337.
Selkoe, D. J. (2001) Presenilns, ß-amyloid precursor protein and the molecular basis of Alzheimer’s disease. Clin. Neurosci. Res. 1: 91-103.
Seubert, P. (1992) Isolation and quantitation of soluble Alzheimer’s β protein from biological fluids. Nature 359: 325-327.
Shahidi, F. & Wanasundara, P. K. J. P. D. (1992) Phenolic antioxidants. Crit. Rev. Food Sci, Nutr. 32: 67-103.
Shukla, C. and Bridges, L. R. (1999). Regional distribution of tau, beta-amyloid and beta-amyloid precursor protein in the Alzheimer’s brains: a quantitative immunolabelling study. Neuroreport 10: 3785-3789.

Shen, H. M. & Ong, C. N. (2000) Detection of oxidative DNA damage in human sperm and its association with sperm function and male infertility. Free Rad. Biol. Med. 28: 529-536.
Shimda, A., Hosokawa, M., Ohta, A., Akiguchi, I. & Takeda, T. (1994) Localization of atrophy-prone areas in the aging mouse brain: comparison between the brain atrophy model SAM-P/10 and the normal control SAM-R/1. Neuroscience 59(4): 859-869.
Shoji, M., Golde, T. E. & Ginso, J. (1992) Production of the Alzheimer amyloid b protein by normal proteolytic processing. Science 258: 126-129.
Sies, H. (1993) Strategies of antioxidant defense. Eur. J. Biochem. 215: 213-219.
Sikka, S. C. (2001) Relative impact of oxidative stress on male reproductive function. Curr. Med. Chem. 8: 851-862.
Simic, M. G. (1988) Mechanisms of inhibition of free-radical processes in mutagenesis and carcinogenesis. Mutat. Res. 202: 377-386.
Sisodia, S. S. (1992) β-amyloid precursor protein cleavage by a membrance bound protease. Proc. Nat. Acad. Sci. USA 89: 6075-6079.
Sisodia, S. S. & Price, D. L. (1995) Role of the β-amyloid protein in Alzheimer’s disease. FASEB. 9: 366-370.
Smith, M. A., Hirai, K., Hsiao, K., Pappolla, M. A., Harris, P. L., Siedlak,S. L., Tabaton, M. & Perry, G. (1998) Amyloid-beta deposition in Alzheimer transgenic mice is associated with oxidative stress. J. Neurochem. 70(5): 2212-2215.
Smith, P., Krohn, R. I., Hermanson, G. T. Mallia, A. K., Gartner, F. H., Prorenzano, M. D., Fujimoto, E. K., Goeke, N. M., Olson, B. T. & Klenk, D. C. (1985) Measurement of protein using bicinchonic acid. Anal. Biochem. 15: 76-85.


Sohal, R. S. & Allen, R. G. (1990) Oxidative stress as a causal factor in differentiation and aging: a unifying hypothesis. Exp. Gerontol. 25: 499.
Squire, L. R. & Zola, S. M. (1996) Structure and function of declarative and nondeclarative memory system. Proc. Natl. Acad. Sci. USA 93: 13514-13515.
Stadtman, E. R. & Oliver, D. N. (1991) Metal catalysed oxidation of proteins. Physiological consequences. J. Biol. Chem. 266: 2005-2008.
Sternberg, D. B., Martinez, J. L., Gold, P. E. & McGaugh, J. L. (1985) Age-related memory deficits in rats and mice. Enhancement with peripheral injection of epinephrine. Behav. Neural. Biol. 44: 213-220.
Sumida, S., Tanaka, K., Kitao, H. & Nakadomo, F. (1989) Exercise-induced lipid peroxidation and leakage of enzymes before and after vitamin E supplementation. Int. J. Biochem. 21(8): 835-838.
Tainer, J. A., Getzoff, E. D., Richardson, J. S. & Richardson, D. C. (1983) Structure and merchanism of copper, zine superoxide dismutase. Nature 306: 284.
Takeda, T. (1999) Senescence-acelerated mouse (SAM): a biogerontological resource in aging research. Neurobiol. Aging 20: 105-110.
Takeda, T., Hosokawa, M. & Higuchi, K. (1991) Senescence-accelerated mouse (SAM): a novel murine model of accelerated senescence. JAGS 39: 911-919.
Takeda, T., Hosokawa, M. & Higuchi, K. (1994) Senescence-accelerated mouse (SAM): A novel murine model of aging. In Takeda, T. (ed.): The SAM model of senescence. Amsterdam. Excerpta. Medica. pp. 15-22.

Takeda, T., Hosokawa, M. & Higuchi, K. (1997) Senescence-accelerated mouse (SAM): a novel murine model of senescence. Exp. Geronol. 32: 105-109.
Takeda, T., Hosokawa, M., Takeshita, S., Irino, M., Higuchi, K., Matsuschita, T., Tomita, Y., Yasuhira, K., Hamamoto, H., Shimizu, K., Ishii, M. & Yamamto, T. (1981) A new murine model of accelerated senescence. Mech. Aging Dev. 17: 183-194.
Tanzi, R. E. (1995) Clinical implications for basic research: A promising animal model for Alzheimer’s disease. New Eng. J. Med. 332: 1512-1513.
Tatum, V. L., Changchit, C. & Chow, C. K. (1990) Measurement of malondialdehyde by highperformance lipid chromatography with fluorescence detection. Lipids 25(4): 226-229.
Thiele, J. J., Friesleben, H. J., Fuchs, J. & Ochsendorf, F. R. (1995) Ascorbic acid and urate in human seminal plasma: determination and interrelationships with chemiluminescence in washed semen. Hum. Reprod. 10: 110-115.
Tomlinson, B. E. (1977) The payhology of dementia. In ” Dementia“(2nd ed) (Eds C. E. Wells) Philadelphia : F. A. Davis. pp. 113-153.
Twigg, J., Lrvine, D. S., Houston, P., Fulton, N., Michael, L. & Aitken, R. J. (1998) Iatrogenic DNA damage induced in human spermatozoa during sperm preparation: protective significance of seminal plasma. Mol. Hum. Reprod. 4: 439-444.
Ursini, F., Maiorino, M., Valente, M., Ferri, L. & Gregolin, C. (1982) Purification from pig liver of a protein which protects liposomes and biomembranes from peroxidative degradation and exhibits glutathione peroxidase activities on phosphatidylcholine hydroperoxides. Biochem. Biophys. Acta. 839: 197-211.
Vance, C. K. & Miller, A. F. (1998) A simple proposal that can explain the inactivity of metal-substitued superoxide dismutase. J. Am. Chem. Soc. 120: 461-467.
Wamer, H. R. (1994) Superoxide dismutase, aging, and degenerative disease. Free Radic. Biol. Med. 17: 249-258.
Wang, M. Y. & Liethr, J. G. (1995) Lipid hydroperoxide-induced endogenous DNA adducts in hamsters: possible mechanism of lipid hydroperoxide-mediated carcinogenesis. Arch. Biochem. Biophys. 316: 38-46.
Wei, Y. H. (1998) Oxidative stress and mitochondrial DNA mutations in human aging. Proc. Soc. Exp. Biol. Med. 217(1): 53-63.
Whishaw, I. Q., Mittleman, G., Bunch, S. T. & Dunnett, S. B. (1987) Impairments in the acquisition, retention, and selection of navigation strategies after medial caudate-putamen lesions in rats. Behav. Brain Res. 24: 125-138.
Willians, W. B., Cuvelier, M. E & Berset, C. (1995) Use of free radical method to evaluate antioxidant activity. Lebe.-Wisse. Technol. 28: 25-30.
Wong, W. Y., Thomas, C. M., Merkus, H. M., Zielhuis, G. A., Doesburg, W. H. & Steegers-Theunissen R. P. (2000) Cigarette smoking and the risk of male factor subfertility: minor association between cotinine in seminal plasma and semen morphology. Fertil. Steril. 74: 930-935.
Wyrobek, A. & Bruce, W. R. (1978) The induction of sperm-shape in mice and humans. In “Chemical mutagens principies and methods for their detection” Hollanender, C. A. Ed., Raven Press, New York. pp. 257-280.
Yagi, H., Katoh, S., Akiguchi, I. & Takeda, T. (1988) Age-related deterioration of ability of acquisition in memory and animal model of disturbance in recent memory. Brain Res. 474: 86-93.




Yamada, K., Tanaka, T., Han, D., Senzaki, K., Kameyama, T. & Nabeshima, T. (1999) Protective affects of idebenone and alpha-tocopherol on beta-amyloid-(1-42)-induced learning and memory deficits in rats: implication of oxidative stress in beta-amyloid-induced neurotoxicity in vivo. 11(1): 83-90.
Yamaguchi, T., Takamura, H., Matoba, T & Terao, J. (1998) HPLC method for evaluation of the free radical-scavenging activity of foods by using 1,1-diphenyl-2-picrydrazyl. Biosci. Biotechnol. Biochem. 62(6): 1201-1204.
Yanming, X. & Keiichi, H. (2002) Amyloid fibril proteins. Mech. Ageing Dev. 123: 1625-1636.
Younkin, S. G. (1995) Evidence that Aβ42 is the real culprit in Alzheimer’s disease. Ann. Neurol. 37: 287-288.
Yuan, R. Y., Wu, M. Y. & Hu, S. P. (2000) Antioxidant status in patients with Parkinson’s disease. Nutr. Res. 20(5): 647-652.
Yuan, Y. V. & Kitts, D. D. (1997) Endogenous antioxidants: Role of antioxidant enzymes in biological system. In “Natural Antioxidants Chemistry, Health Effects, Applications.” Shahidi, F., Ed., New Foundland, Canada. pp. 258-270.
Zaidi, S. M. K. R. & Banu, N. (2004) Antioxidant potential of Vitamins A, E and C in modulating oxidative stress in rat brain. Clin. Chem. Acta. 340: 229-233.