本研究以耐酸耐膽鹽的乳酸桿菌和雙叉乳桿菌共八株益生菌，測定其所製成之發酵乳抗氧化能力。挑選出其中抗氧化能力較佳的菌株，再測定其免疫特性。
抗氧化能力方面，發酵乳之抗氧化能力較發酵乳之析出乳清和發酵乳之沉降凝乳為佳。其中以B. adolescentis CCRC 14607為菌元之發酵乳的抗氧化性最好，與1 mg/ml BHT相當；B. catenulatum CCRC 14667為菌元之發酵乳的還原力最佳，可達1 mg/ml BHT的68%；清除超氧陰離子能力方面以L. bulgaricus CCRC 14009為菌元的發酵乳之沉降凝乳清除能力最好；清除DPPH自由基能力方面，L. acidophilus CCRC 10695為菌元之發酵乳清除率與Vit. C相等；螯合亞鐵離子能力方面， L. brevis CCRC 12187為菌元之發酵乳的螯合能力與1 mg/ml EDTA相當；清除過氧化氫能力方面，以L. bulgaricus CCRC 14009、B. bifidum CCRC 14670為菌元之發酵乳較高；清除氫氧自由基方面，L. bulgaricus CCRC 14009之菌體清除率達42%。
綜合抗氧化能力，選出B. adolescentis CCRC 14607、B. catenulatum CCRC 14667、L. acidophilus CCRC 10695及L. brevis CCRC 12187進行免疫特性之測定。
生體外激活巨噬細胞產TNF-α的能力以菌體最強，去菌液次之，發酵乳最弱，又以L. brevis CCRC 12187菌體的激活能力最強。而發酵乳甚至能抑制巨噬細胞產生TNF-α。激活巨噬細胞分泌IL-6方面，以去菌液最強，發酵乳次之，菌體最弱。在去菌液中又以L. brevis CCRC 12187的刺激能力最強。激活巨噬細胞分泌一氧化氮方面，去菌液與菌體激活巨噬細胞的能力相當，但發酵乳的能力較差，L. brevis CCRC 12187與B. catenulatum CCRC 14667甚至較對照組為低。
利用以上益生菌製成發酵乳後餵飼懷孕母鼠，對母鼠的體重沒有明顯的影響。母鼠糞便中乳酸桿菌的含量，在餵飼發酵乳後有所提升。母鼠血液中IgG的含量，各處理組間沒有明顯的差異。隨著餵飼期間增長，母鼠糞便中IgA也跟著增加。其中以B. adolescentis CCRC 14607組增加的最多。各處理組仔鼠糞便中IgA的含量都較對照組為高。

Lactic acid bacteria and bifidobacteria were widely used as probiotics in foods. As consumers concern more about health, the fermented milk of probiotics become more popular. Probiotics improve the balance of intestinal flora, which exert beneficial effects by decreasing harmful bacterial metabolites such as amines and indoles. Some probiotic bacteria have been found to enhance the immunity of the host and prevention of infectious diseases.
The purposes of this study were to examine the antioxidant activity and immunomodulating effect of lactic acid bacteria and bifidobacteria fermented milk. The strains have previously shown the antioxidant activity, the tolerance of gastric acid and bile salts by whole cells.
Eight strains of probiotics were selected for antioxidant activity test. The fermented milk had better antioxidant activity than the centrifugal whey and curd of fermented milk. B. adolescentis CCRC 14607 predented the best antioxidant activity by the inhibition of linoleic acid oxidation and it was equal to 1 mg/ml BHT. B. catenulatum CCRC 14667 was the best for reducing activity and it achieved 68% of 1 mg/ml BHT. L. acidophilus CCRC 10695 showed the commensurate scavenging effects on α-diphenyl-2-picryl hydrazyl (DPPH．) radical as vitamin C. In respect of chelating effect on Fe2+, L. brevis CCRC 12187 was equal to 1 mg/ml EDTA. L. bulgaricus CCRC 14009 and B. bifidum CCRC 14670 both represented the greatest ability of scavenging H2O2. The scavenging effects of L. bulgaricus CCRC 14009 on hydroxyl radicals reached 42%.
Comparing the antioxidant activity of the eight strains, we selected B. adolescentis CCRC 14607、B. catenulatum CCRC 14667、L. acidophilus CCRC 10695 and L. brevis CCRC 12187 were selected to test their effect on immunity.
In order to study the effect on macrophage activation of probiotics, cytokines, H2O2 and NO which was secreted from mouse macrophage cell line RAW 264.7 were examined. The cells were incubated with latic acid bacteria cells, the spent culture supernatant and the fermented milk. The cells of L. brevis CCRC 12187 were the most powerful stimulus for TNF-α production although the fermented milk of some strains could inhibit it. The cells and the cultured broth of probiotics represented the same activation level on macrophage. The fermented milk of L. brevis CCRC 12187 and B. catenulatum CCRC 14667 showed much lower level than control group.
The in vivo test of these four strains were studied. The pregnant mice were fed with the reconstituted fermented milk of probiotics. During the period of administration, there were no significant difference on body weight and IgG level in the blood of mother mice. As the time of administration increased, more fecal IgA were indentified. B. adolescentis CCRC 14607 was the most significant strain. All the dams of these mice had higher IgA level than the control group.

壹、中文摘要 1
貳、前言 2
參、文獻檢討 3
一、乳酸菌基本特性 3
二、雙叉乳桿菌基本特性 3
三、益生菌基本特性 3
四、乳酸菌和雙叉乳桿菌作為益生菌之特點 4
(一) 人體常駐菌叢 4
(二) 具耐胃酸及膽鹽能力 4
(三) 具吸附腸道上皮細胞能力 4
(四) 能於消化道中增殖 5
(五) 產抗有害菌物質 5
五、乳酸菌和雙叉乳桿菌對人體之生理功能 7
(一) 維持腸道菌相平衡 7
(二) 刺激活化免疫能力 7
(三) 抗氧化能力 7
(四) 降低腸道癌症發生機率 8
(五) 降低血中膽固醇含量 9
(六) 合成並提供維生素 9
(七) 減緩乳糖不耐症 9
六、乳酸菌和雙叉乳桿菌與抗氧化 9
(一) 活性氧之作用與傷害 9
(二) 抗氧化劑作用機制 11
(三) 天然抗氧化劑 12
(四) 乳酸菌與抗氧化 12
七、乳酸菌及雙叉乳桿菌與腸道免疫 13
(一) 腸道免疫系統 13
(二) 巨噬細胞的活化 15
(三) 乳酸菌與腸道免疫 16
肆、實驗部分 17
第一部分 益生菌與其發酵乳抗氧化能力之探討 17
壹、摘要 18
貳、前言 19
參、材料與方法 20
肆、結果與討論 26
一、抗氧化性的測定 26
二、還原力的測定 31
三、清除超氧陰離子能力的測定 33
四、清除DPPH自由基能力的測定 36
五、螯合亞鐵離子能力的測定 38
六、清除過氧化氫能力的測定 41
七、清除氫氧基自由基能力的測定 43
第二部分 益生菌與其發酵乳生物體外免疫功能之探討 52
壹、摘要 53
貳、前言 53
參、材料與方法 54
肆、結果與討論 59
一、益生菌與其發酵乳激活巨噬細胞產生TNF-α量 59
二、益生菌與其發酵乳激活巨噬細胞產生IL-6量 62
三、益生菌與其發酵乳激活巨噬細胞產生NO量 64
第三部分 益生菌與其發酵乳生物體內免疫功能之探討 66
壹、摘要 67
貳、前言 67
參、材料與方法 68
肆、結果與討論 73
一、益生菌發酵乳餵飼母鼠期間體重變化 73
二、益生菌發酵乳餵飼母鼠糞便乳酸桿菌數變化 73
三、益生菌發酵乳餵飼母鼠之血液IgG含量 73
四、益生菌發酵乳餵飼母鼠之糞便IgA含量 78
五、益生菌發酵乳餵飼母鼠所產仔鼠之糞便IgA含量 80
伍、結論 80
陸、參考文獻 81
柒、英文摘要 93

林彣郁。2001。國立中興大學畜產學系碩士論文。乳酸菌和雙叉乳桿菌益生特性之探討。台中。台灣。
陳維泰。2001。國立中興大學畜產學系碩士論文。不同動物黑色素萃取物的物理化學及功能特性之探討。台中。台灣。
傅麒玲。1999。腸道菌群與腸道免疫功能的評估方法。食品工業 31(12): 14-25。
趙瑞益。1995。國立清華大學生物醫學研究所碩士論文。鎘誘發中國倉卵巢細胞的分子致突變機制：含氧自由基的參與。新竹。台灣。
蔡淑瑤。2002。國立中興大學食品科學系碩士論文。靈芝與柳松菇之抗氧化性質和其對腫瘤細胞之毒性及柳松菇之抗致突變性質。台中。台灣。
賴怡君。1999。國立中興大學食品科學系碩士論文。乳酸菌之抗氧化性及抗致突變性對細胞株Intestine 407之影響。台中。台灣。
Abbas, A. K., A. H. Lichtman, and J. S. Pober. 2000. Cellular and Molecular Immunology. (4 Ed). pp. 125-160. W. B. Saunders.USA.
Abee, T., L. Krockel, and C. Hill. 1995. Bacteriocins: modes of action and potentials in food preservation and control of food poisoning. Int. J. Food Microbiol. 28: 169-185.
Acker, S. B. E., Balen, G. P., Berg, D. J., Bast, A. and Vijgh, W. J. F. 1998. Influence of iron chelation on the antioxidant activity of flavonids. Biochem. Pharmacol. 56: 935-943.
Ahotupa M., M. Saxelin, and R. Korpela. 1996. Antioxidative properties of Lactobacillus GG. Nutr. Today Suppl. 31: 51S-52S.
Akimitsu T., M. Takeshi, S. Mikiko, N. Koji, M. Masami, and Y. Teruo. 2001. Enhancement of natural killer cytotoxicty delayed murine carcinogenesis by a probiotic microorganism. Carcinogenesis 22(4): 599-605.
Alican, I., and P. Kubes. 1996. A critical role for nitric oxide in intestinal barrier function and dysfuntion. Am. J. Physiol. 270: G225-G237.
Ames, B. N., M. K. Shigenaga, and T. M. Hagen. 1993. Oxidants, antioxidants and the degenerative diseases of aging. Proc. Natl. Acad. Sci. USA 90: 7915-7922.
Annika, M. M., M. Manninen, and H. Gylienbery. 1983. The adherence of lactic acid bacteria to the columnar epithelial cells of pigs and calves. J. Appl. Bacteriol. 55: 241-245.
Archibald F. S. and I. Fridovich. 1981. Manganese, superoxide dismutase, and oxygen tolerance in some lactic acid bacteria. J. Bacteriol. 146: 828-936.
Aruoma, O., M. Laughton, and B. Halliwell. 1989. Carnosine, homocarnosine and anserine: could they act as antioxidants in vivo? Biochem. J. 264: 863-869.
Athina, A., J. S. Eddy., H. J. B. Marjon, and G. M. G. Leon. 2001. Antioxidative properties of Lactobacillus sake upon exposure to elevated oxygen concentrations. FEMS Microbiol. Lett. 203; 87-94.
Axelsson, L., T. C. Chhung, W. J. Dobrogosz, and S. Lindgren. 1989. Discovery of a broad-spectrum antimicrobial substance provided by L. ruteri. Microbiol. Ecol. Health Dis. 2: 131-136.
Baker E. N., H. M. Baker, N. Koon, and R. D. Kidd. 2002. Lactoferrin: bioactive properties and applications. Bulletin Int. Dairy Federation 375:54-58.
Balkwill, F. 2000. Cytokine cell biology. (3 Ed). pp. 1-100. Oxford UK.
Baricault L., G. Denariaz, J. J. Houri, C. Bouley, C. Sapin, and G. Trugnan. 1995. Use of HT-29, a cultured human colon cancer cell line, to study the effect of fermented milks on colon cancer cell growth and differentiation, Carcinogenesis 16: 245-252.
Barrow, P. A., B. E. Brooder, R. Fuller, and M. J. Newport. 1980. The attachment of bacteria to the epithelium of the pigs and its importance in the microecology of the intestinal. J. Appl. Bacteriol. 48: 147-154.
Barry R. G., J. G. Lisa, and P. M. Ronda. 1996. The effect of Lactobacillus GG on the intitiation and promotion of DMH-induced intestinal tumors in the rat. Nutr. and Cancer 25: 197-204.
Benno, Y., Mitsuoka, T., 1992. Impact of Bifidobacterium longum on human. Microbiol. Immunol. 36: 683-694.
Beutler, B., D. Greenwald, and J. D. Hulmes. 1986. Identity of tumour necrosis factor and the macrophage secreted factor cachectin. Nature 316: 552-554.
Bezkorovainy, A., E. Kot, and S. Furmanov. 1995. Ferrous iron oxidation by Lactobacillus acidophilus and its metabolic products. J. Agric. Food Chem. 43: 1276-1282.
Bezkorovainy, A., E. Kot, and S. Furmanov. 1996. Hydrogen peroxide production and oxidation of ferousiron by Lactobacillus delbrueckii ssp. bulgaricus. J. Dairy Sci. 79: 758-766.
Bezkorovainy, A., E. Kot, and S. Furmanov. 1997. Binding of Fe(OH)3 to Lactobacillus delbrueckii ssp. bulgaricus and Lactobacillus acidophilus: apparent role of hydrogen peroxide and free radicals. J. Agric. Food Chem. 45: 690-696.
Bhatia S. J., N. Kochar, and P. Abraham. 1989. Lactobacillus acidophilus inhibits growth of campylobacter pylori in vitro. J. Clin. Microbiol. 27: 2328-2330
Blois, M. S. 1958. Antioxidant determination by the use of a stable free radical. Nature 26: 1199-1200.
Bolann, B. J. and R. J. Ulvik. 1990. On the limited ability of superoxide to release iron from ferritin. Eur. J. Biochem. 193: 899-904.
Brandtzaeg P., T. S. Halstensen, K. Kett, P. Kraje, D. Kvale, T. O. Rognum, H. Scott, and L. M. Sollid. 1989. Immunobiology and immunopathology of human gut mucosa: humunal immunity and intraepithelial lymphocyte. Gastroenterology 97: 1562-1584.
Brandtzaeg, P. 1995. Molecular and cellular aspects of the secretory immunoglobylin system. Acta Pathologica, Microbiologica et immunologica Scandinavica 103: 1-19.
Brand-Williams, W., M. E. Cuveliver, and C. Berset. 1995. Use of a free radical method to evaluate antioxidant activity. Lebensm-Wiss. U. Technol. 28: 25-30.
Branen, A. L. 1975. Toxicology and biochemistry of butylated hydroxyl anisole and butylated hydroxytoluene. J. Am. Oil Chem. Soc. 52: 59-63.
Cerutti, P. A. 1985. Prooxidant states and tumor promotion. Science 227: 375-381.
Cervato G., R. Cazzola, and B. Cestaro. 1999. Studies on the antioxidant activity of milk caseins. Int. J. Food Sci. Nutr. 50 (5): 291-296.
Chan, R. C. Y., G. Reid, R. T. Irvin, A. W. Bruce and J. W. Costerton. 1985. Competitive exclusion of uropathogens from human uroepithelial cells by Lactobacillus whole cells and cell wall fragments. Infect. Immunol. 47: 84-89.
Chance, B., H. Sies, and A. Boveris. 1979. Hydroperoxide metabolism in mammalian organs. Physiol. Rev. 59: 527-605.
Chantal M., C. V. Juan, M. Marcela, R. Mirtha, and P. Gabriela. 2001. Immunomodulating effects of milks fermented by Lactobacillus helveticus and its non-proteolytic variant. J. of Dairy Res. 68: 601-609.
Charley, B. 1996. Effects of immunopotentiating agents on alveolar macrophage properties. Comp. Immun. Microbiol. Infect. Dis. 9: 155-159.
Cheng, K. C., D. S. Cahill, H. Kasai, S. Nishimura, and L. A. Loeb. 1992. 8-hydroxyguanine, an abundant form of oxidative DNA damage, cause GT and AC substitution. J. Biol. Chem. 267: 166-172.
Chevalier, P., D. Roy, and P. Ward. 1990. J. Appl. Bacteriol. 68: 619-624.
Coconnier, M. H., T. R. Klaenhammer, S. Kerneis, M. F. Bernet, and A. L. Servin. 1992. Protein-mediated adhesion of Lactobacillus acidophilus BG2F04 on human enterocyte and mucus-secreting cell lines in culture. Appl. Enviro. Microbiol. 58: 2034-2039.
Condon, S., 1987. Responses of lactic acid bacteria to oxygen. FEMS Microbiol. Rev. 46: 269-280.
Conway, P. L., S. L. Gorbach, and B. R. Goldin. 1987. Survival of lactic acid bacteria in the human stomach and adhesion to intestinal cells. J. Dairy Sci. 70: 1-12.
Daglia, M., A. Papetti, C. Dacarro, and G. Gazzani. 1998. Isolation of an antibacterial component from roasted coffee. J. Pharm. Biomed. Anal. 18: 219-225
Dahiya, R. S. and L. Speak. 1968. Hydrogen peroxide formation by lactobacilli and its effect on Staphylcoccus aureus. J. Dairy Sci. 51: 1568-1572.
De Simone, C., R. Vesely, B. Bianchi Salvadori, and E. Jirillo. 1993. The role of probiotics in modulation of the immune system in man and in animals. Int. immunother. 9: 23-28.
De Vos W. M. 1996. Metabolic engineering of sugar catabolism in lactic acid bacteria. Antonie van Leeuwenhoek 70: 223-242.
De Vries, W. and A. H. Stouthamer. 1967. J. Bacteriol. 93: 574-576.
Decker, E. A. and H. Faraji. 1990. Inhibition of lipid oxidation by carnosine. J. Am. Oil Chem. Soc. 67: 650-652.
Decker, E. A., A. D. Crum, and J. T. calvert. 1992. Differences in the antioxidant mechanism of carnosine in the presence of copper and iron. J. Agrc. Food Chem. 40: 756-759.
Denter, J. and B. Bisping. 1994. Formation of B-vitamins by bacteria during the soaking process of soybeans for temper fermentation. Int. J. Food Microbiol. 22(1): 23-31.
Desjardins, M. L., D. Roy, and J. Goulet. 1990. J. Dairy Sci. 73: 299-307.
Dinis, T. C. P., V. M. C. Madeira, and L. M. Almeida. 1994. Action of phenolic derivatives (acetaminophen, salicylate, and 5-aminosalicylate) as inhibitors of memvrane lipid peroxidation and as peroxyl radical scavengers. Arch. Biochem. Biophys. 315: 161-169.
Doores, S. 1993. Organic Acids. pp. 95-136. Marcel Dekker. USA.
Draper, H. H., S. Agarwal, D. E. Nelson, J. J. Wee, A. K. Ghoshal, and E. Farber. 1995. Effects of peroxidative stress and age on the concentration of a deoxyguanosine-malonialdehyde adduct in rat DNA. Lipids 30: 959-961.
Dziezak, J. D. 1986. Preservatives: Antioxidants. Food Technol. 40: 94-102.
Elina, M. T., C. O. Arthur, and J. S. Seppo. 1999. The effect of probiotic bacteria on the adhesion of pathogens to human intestinal mucus. Immunol. Med. Microbiol. 26: 137-142.
Farmer, E. H., G. F. Bloomfield, A. Sundralingam, and D. A. Sutton. 1942. The course and mechanism of autoxidation reactions in olefinic and polyolefinic substances, including rubber. Trans. Faraday Soc. 38: 348-356.
Farr, S. B. and T. Kogoma. 1991. Oxidative stress responses in Escherichia coli and Salmonilla typhimurium. Microbiol. Rev 55: 561-585.
Ferguson, L. R. 1994. Antimutagens as cancer chemopreventive agents in the diet. Mutation Res. 307: 395-410.
Fridovich, I. 1995. Superoxide radical and superoxide dismutases Annu. Rev. Bochem. 64: 97-112.
Fukuchima, Y., Y. Kawata, M. Koko, K. Jun-ichi, and M. Tomotari. 1999. Effect of bifidobacteria feeding on fecal flora and production of immunoglobulins in lactating mouse. Int. J. Food Microbiol. 46: 193-197.
Fukushiama, Y., Y. Kawata., K. Mizumachi., J. Kurisaki. and T. Mitsuoka., 1999. Effect of bifidobacteria feeding on fecal flora and production of immunoglobulins in lactating mouse. Int. J. Food Microbiol. 46: 193-197.
Fukushima, M. and M. Nakano. 1996. Effects of a mixture of organisms Lactobacillus acidophilus of Streptococcus faecalis on cholesterol metabolism in ratsfed on a fat- and cholesterol-enriched diet. Br. J. Nutr. 76: 857-867.
Fukushima, Y., Kawata, Y., Hara, H., Terada, A., Mitsuoka, T., 1998. Effect of probiotic formula on intestinal immunoglobulin A production in healthy children. Int. J. Food Microbiol. 42: 39-44.
Fuller, R. 1978. Epithelial attachment and other factors controlling the colonization of the intestine of the gnotobiotic chichen by lactobacilli. J. Appl. Bacteriol. 45: 389-395.
Fuller, R. 1986. Probiotics. J. Appl. Bacteriol. 61: 1-7
Fuller, R. 1989. Probiotics in man and animals. J. Appl. Bacteriol. 66: 365-378.
Fuller, R. and B. E. Brooker. 1973. Ecological studies on the Lactobacillus flora associated with the crop epithelium of the fowl. Am. J. Clin. Nutr. 27: 1305-1312.
Ganzle, M. G., A. Holtzel, J. Walter, G. Jung, and W. P. Hammes. 2000. Charactenization of reutericyclin produced by Lactobacillus reuteri LTH2584. Appl. Environ. Microbiol. 66: 4233-4333.
Giannella, R. A., S. A. Broitman, and N. Zamcheck. 1972. Gastric acid barrier to ingested microorganisms in man. Studies in vivo and in vitro. Gut. 13: 251-256.
Gill, H. S. 1998. Stimulation of the immunue system by lactic cultures. Int. Dairy J. 8: 535-544.
Gilliland, S. E. 1979. Beneficial interrelationships between certain microorganism and humans: candidate microorganisms for use as dietary adjuncts. J. Food Prot. 42: 164-167.
Gilliland, S. E., and D. K. Walker. 1990. Factors to condiser when selecting a dietary adjunct to produce a hypocholesteroleric effect in humans. J. Dairy Sci. 73: 905-911.
Giulivi, C., A. Boveris, and E. Cadenas. 1995. Hydroxyl radical generation during mitochondrial electron transfer and the formation of 8-hydroxydeoxyguanosine in mitochondrial DNA. Arch. Biochem. Biophys. 316: 909-916.
Goldin, B. R. and S. L. Gorbach. 1984. The effect of milk and Lactobacillus feeding on human intestinal bacterial enzyme activity. Am. J. Clin. Nutr. 39: 756-761.
Gordon, M. H. 1990. The mechanism of antioxidant action in vitro. In Food Antioxidants. pp. 1-18. Elsevier Applied Science. London and New York.
Graeme H. M., J. P. Peter., and J. P. Martin. 1999. A probiotic Strain of L. acidophilus reduces DMH-induced large intestinal tumors in male Sprague-dawley rats. Nutr. and Cancer. 35(2): 153-159.
Greshwin, L. J., S. Krakwka and R. G. Olsen. 1995. Immunology and immunopathology of domestic animals. (2 Ed). pp. 1-100. Mosby. USA.
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.
Gutteridge, J. M. C. 1995. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin. Chem. 41: 1819-1828.
Gutteridge, J. M. C. and G. J. Quinlan. 1993. Antioxidant protection against organic and inorganic oxygen radicals by normal human plasma: the important primary role for iron-binding and iron-oxidising proteins. Biochem. Biophys. Acta. 1156: 144-150.
Gutteridge, J. M. C. and Halliwell, B. 1994. Antioxidants in Nutrition, Health, and Disease. pp. 1-100. Oxford University Press, UK.
Halliwell, B. 1995. Antioxidant characterization, methodology and mechanism. Biochem. Pharmacol. 49: 1341-1348.
Halliwell, B. 1998. Can oxidative DNA damage be used as a biomarker of cancer risk in humans? Problems, resolutions and preliminary results from nutritional supplementation studies. Free radical Res. Commun. 25: 469-486.
Halliwell, B. 1999. Oxygen and nitrogen are pro-carcinogens. Damage to DNA by the effects of nutrition. Mutat. Res. 443: 37-52.
Halliwell, B. and J. M. C. Gutteridge. 1990. Role of free radicals and catalytic metal ions in human disease. Methods Enzymol. 186: 1-85.
Halliwell, B. and J. M. C. Gutteridge. 1998. Free Radical in Biology and Medicine. pp. 25-86. Clarendon Press, UK.
Halliwell, B. and J. M. Gutteridge. 1985. Free radical s in biology and medicine. pp. 16-79. Clarendon Press . London/New York.
Halliwell, B. and J. M. Gutteridge. 1989. Free radicals in biology and medicine. (2 Ed). pp. 49-73. Clarendon Press. UK.
Halliwell, B. and S. Chirico. 1993. Lipid peroxidation: its mechanism, Measurement, and significance. Am. J. Clin. Nutr. 57: 715s-725s.
Halliwell, B., J. M. C. Gutteridge, and O. I. Aruoma. 1987. The deoxyribose method: A sample “test-tube” assay for determination of rate consistants for reactions of hydroxyl radicals. Anal. Biochem. 165: 215-219.
Halliwell, B., M. A. Murcia, S. Chirico, and O. I. Aruoma. 1995. Free radicals and antioxidants in food and in vivo: what they do and how they work. Crit. Rev. Food Sci. Nutr. 35: 7-20.
Harsharnjit S. G. and J. R. Kay. 2001. Probiotic supplementation to enhance natural immunity in the elderly: effects of a newly characterized immunostimulatory strain Lactobacillus rhamnosus HN001 (DR20TM) on leucocyte phagocytosis. Nutr. Res. 21: 183-189.
Hartemink R., V. R. Domenech, and F. M. Rombouts. LAMVAB─A new selective medium for the isolation of lactobacilli from faeces. 1997. J. Microbiol. Methods 29: 77-84.
Harvenaar, R., B. T. Brink, and J. H. J. Huis In’t Veld, 1992. Selection of strains for probiotics use in “Probiotics, The scientific basis.” pp. 209-222. USA.
Hentges, D. J. 1983. Biotransformation of bile acids and cholesterol by the intestinal microflora. Hunam intestinal microflora in health and disease. pp. 25-86. Academic Press. New York:
Hirano, T. 1992. The biology of interleukin-6. Chem. Immunol. 51: 153-180.
Hiromi K., S. Masahiro., N. Hajime, and S. Yutaka. 1993. Effect of antioxidative lactic acid bacteria on rats fed a diet deficient in vitamin E. J. Dairy Sci. 76: 2493-2499.
Hoijer M. A., M. J. Melief, C. G. Helden-Meeuwsen, F. Eulderink, M. P. Hazenberg. 1995. Detection of muramic acid in a carbohydrate fraction of human spleen. Infect. & Immun
. 63(5): 1652-1657.
Holtzel, A., M. G. Ganzle, G. J. Nicholson, W. P. Hammes, and G. Jung. 2000. The first low-molecular-weight antibiotic from lactic acid bacteria: reutericyclin, a new tetramic acid. Angewandte Chemic. International Edition 39: 2766-2768.
Hyslop, P. A., D. B. Hinshaw, W. A. Halsey, J. H. Jackson, and C. G. Cochrane, 1988. Mechanisms of oxidant-mediated injury. J. Biol. Chem. 263: 1665-1675.
Ignarro, L. J., J. M. Fukato, J. M. Griscavage, N. E. Rogers. and R. E. Byrns. 1993. Proc. Natl. Acad. Sci. 90: 8103-8107.
Imada, K., S. Fukushima, T. Shivai, M. Ohtani, K. Nakanishi, and N. Ito. 1983. Promoting activities of butylated hydroxyanisole and butylated hydroxytoluene on 2-stage urinary bladder carcinogenesis and inhibition of γ-glutamyl transpeptidase-positive foci development in the liver of rats. Carcinogenesis 4:885-889.
Ishikawa, Y. 1992. Development of new types of antioxidants from microbial origin. J. Jpn. Oil Chem. Soc. 41: 762-767.
Ito, N., S. Fukushima, and H. Tsuda. 1985. Carcinogenicity and modification of the carcinogenic response by BHA, BHT and other antioxidants. CRC Crit. Rev. Toxical. 15: 109-150.--
Jay, J. M. 1983. Antimicrobial properties of diacetyl. Appl. Environ. Microbiol. 44: 525.
Jiang, T., A. Mustapha, and D. A. Savaiano. 1996. Improvement of lactose digestion in humans by injection of unfermented milk containing Bifidobacterium longum. J. Dairy Sci. 79: 750-757.
Judy, V. W., L. K. Carl, and M. E. Gershwin. 1999. The influence of chronic yogurt consumption on immunity. J. Nutr. 129: 1492s-1495s.
Kaizu, H., M. Sasaki, H. Nakajima, and Y. Suzuki. 1993. Effect of antoixidative lactic acid bacteria on rats fed a diet deficient in vitamin E. J. Dairy Sci. 76: 2493-2499.
Kang, D. K. and D. Y. C. Fung. 1999. Effect of diacetyl on controlling Eschericia coli O15:7H7 and Salmonella typhimurium in the presence of starter culture in a laboratory medium and during meat fermentation. J. Food Prot. 62(9): 975-979.
Kazuhiro H. and R. Joseph. 2000. The role of probiotic bacteria in cancer prevention. Microbes infect. 2: 681-686.
Kegrer, J. P. 1993. Free radicals as mediators of tissue injury and disease CRC Crit. Rev. Toxicol., 23: 21-48.
Klaenhammer, T. P. 1993. Genetics of bacteriocins produced by lactic acid bacteria. FEMS Microbiol. Rev. 12: 39-86.
Korpela, R., T. Peuhkuri, T. Lahteenmaki, E. Sievi, M. Saxelin, and H. Vapaatalo. 1997. Lactobacillus rhamnosus GG shows antioxidative properties in vascular endothelial cell culture. Michwissenschaft. 52: 503-506.
Kudoh Y., S. Matsuda, K. Igoshi, and T. Oki. 2001. Antioxidative peptide from milk fermented with Lactobacillus delbrueckii subsp. bulgaricus IFO13953. J. Jap. Soci. Food Sci. Technol. 48 (1): 44-50.
Labuzq, T. P. 1971. Kinetics of lipid oxidation in food. Crit. Rev. Food Technol. 355-396.
Lagerange, P. H. and B. Hurtrel. 1986. Activities does immunostimulants sur la phagocytose et activites derives. Comp. Immun. Microbiol. Infect. Dis. 9: 143-153.
Lee. H., N. Rangavajhyala, C. Grandjean, and K. M. Shahani. 1996. Anticarcinogenic effect of L. acidophilus on N-nitrosobis (2-oxopropyl) amine induced colon tumor in rats. J. Appl. Nutr. 48: 59-65.
Lee. Y. K. and S. Salminen. 1995. Trends in food Sci. Technol. 6(7): 241-245.
Lefer, A. M., and D. J. Lefer. 1999. Nitricoxide. II. Nitric oxide protects in intestinal inflammation. Am. J. Physiol. 276: G572-G575.
Lidbeck, A. E., O. J. Rafter, C. E. Nord, and J. A. Gustafsson. 1992. Effect of lactobacillus acidophilus supplements on mutagen excretion in faeces and urine in humans. Microbiol. Ecol. Health Dis. 5: 59-67.
Lilly D. M. and R. H. Stillwell. 1965. Probiotics : growth promoting factors produced by microorganism. Science 47: 747-748.
Lin, M. Y. and C. L. Yen. 1999.(a) Antioxidative ability of lactic acid bacteria. J. Agric. Food Chem. 47: 1460-1466.
Lin, M. Y., and C. L. Yen. 1999.(b) Reactive oxygen species and lipid peroxidation product-scavenging ability of yogurt organisms. J. Dairy Sci. 82: 1629-1634.
Lingnert, H., K. Vallentin, and C. E. Eriksson. 1979. Measurement of antioxidant effect in model system. J. Food Proc. Presv. 3; 87-103.
Link-Amster H., F. Rochat, and Y. Saudan. 1994. Modulation of a specific humoral immune response and changes in intestinal flora mediated through fermented milk intake. FEMS Immunol Med. Microbiol. 10: 55-64.
Liu, F., V. E. C. Ooi, and S. T. Chang. 1997. Free radical scavenging activities of mushroom polysaccharide extracts. Life Sci. 60:763-771.
Lorsbach, R. B., W. J. Murphy, C. J. Lowenstein, S. H. Snyder, and S. W. Russell. 1993. Expression of the nitric oxide synthase gene in mouse macrophages activated for tumor cell killing. pp. 25-86. USA.
Machinger, S. and R. Moss. 1986. Cow’s milk allergy in breast-fed infants: The role of allergen and maternal secretory IgA antibody. J. allergy Clin. Immunol. 77: 341-347.
Mager, W. H., and A. J. J. De Kruijff. 1995. Stress-induced transcriotional activation. Microbiol. Rev. 59: 506-531.
Mara L. S., D. T. Manuela, and M. Marina. 2001. Determination of peroxy radical-scavenging of lactic acid bacteria. Int. J. Food Microbiol. 64: 183-188.
Marin L. M., M. V. Tejada-simon., J. Murtha., Z. Ustunol. and J. J. Pestka. 1997. Effects of Lactobacillus spp. On cytokine production by RAW 264.7 macrophage and EL-4 thymoma cell lines. J. of Food Protect. 60: 1364-1370.
Matar, G., J. Coulet, R. Bernier, and E. Brochu. 2000. Bioactive peptides from fermented foods: their role in the immune system. In Probiotics 3. Immunnomodulation by the gut microflora and probiotics. pp.193-209. Kluwer aeademic Publishers. Netherlands.
Metchnikoff, E. 1908. Prolongation of life. Putnam. New York.
Michael, R. 2002. Hydrogen peroxide as second messenger in lymphocyte activation. Nature immunol. 3(12): 1129-1133.
Misuoka, T. 1990. Bifidobacteria and their role in human health. J. Ind. Microbiol. 6: 263-268.
Miyauchi, H., A. Kaino, I. Scinoda, Y. Fukuwatari, and H. Hayasawa. 1997. Immunomodulating effect of bovine lactoferin pepsin hydrolysate on murine splenoxytes and Peyer.s patch cells. J. of Dairy Sci. 80: 2330-2339.
Murakami, H., T. Asakawa, J. Terao, and S. Matsushita. 1984. Antioxidative stability of tempeh and liberation of isoflavones by fermentation. Agric. Biol. Chem. 48: 2971-2975.
Murrell, G. A. C., M. J. O. Francis, and L. Biomley. 1990. Modulation of fibroblast proliferation by oxygen free radicals. Biochem. J. 265: 659-665.
Namiki, M. 1990. Antioxidants/antimutagens in food. Crit. Rev. Food Sci. Nutr. 29: 273-300.
O’sulivan, M. G., G. Thornton, G. C. O’sullivan, and J. K. Co’llins. 1992. Probiotic bacteria: myth or reality? Trends Food Sci. Technol., 3: 309-314.
Okamoto G., G. Hayase, and H. Kato. 1992. Scavenging of active oxygen species by glycated proteins. Bioxci. Biotech. Bichem. 56(6):928-931.
Okazaki, M., S. Fujikawa, and N. Matsumomo. 1990. Effect of xylooligosacharide on the growth of bifidobacteria. Bifidobacteria Microflora. 9:77-86.
Orrhage K., E. Sillerstrom, J. A. Gustafsson, C. E. Nord, and J. Rafter. 1994. Binding of mutagenic heterocyclic amines by intestinal and lactic acid bacteria, Mutat. Res. 311: 239-248.
Oyaizu, M. 1986. Antioxidative activity of browning products of glucosamine fractionated by organic solvent and thin-layer chromatography. Nippon shokuhin kogyo Gakkaishi. 35: 771-775.
Park Y. S., G. E. Ji., Y. T. Ko., H. K. Jung. and Z. Ustunol. 1999. Potentiation of hydrogen peroxide, nitric oxide, and cytokine production in RAW 264.7 macrophage cells exposed to human and commercial isolates of Bifidobacterium. Int. J. of Food Microbiol. 46: 231-241.
Parker, R. B. 1974. Probiotic, the other half of the antibiotic story. Anim. Nutr. Health 29: 4-8.
Paul Ross R., S. Morgan, and C. Hill. 2002. Preservation and fermentation: past, present and future. Int. J. Food Microbiol. 79: 3-16.
Perdigon, G., E. Vintint, S. Alvarez, M. Medina, and M.Medici. 1999. Study of the possible mechanism involved in the mucosalimmune system activation by lactic acid bacteria. J. Dairy Sci. 82: 1108-1114.
Perdigon, G., S. Alvarez, M. Rachid, G. Aguero, and N. Gobbato. 1995. Immune system stimulation by probiotics. J. Dairy Sci. 78: 1597-1606.
Quan S. and S. G. Harsharnjit. 2002. Immune protection mediated by the probiotic Lactobacillus rhamnosus HN001 (DR20TM) against Escherichia coli O157:H7 infection in mice. FEMS Immunol. Medical Microbio. 34: 59-64.
Ramarathnam, H., T. Osawa, H. Ochi, and S. Kawakish. 1995. The contribution of lent food antioxidants to human health. Trends Food Sci. Technol. 6(3): 75-82.
Rambaud, J. C., Y. Bouhnik, P. Marteau, and P. Pochart. 1993. Manipulation of the human gut microflora. Proc. Nutr. Soc., 52: 357-366.
Ramel, C., U. K. Alekperov, B. N. Ames, T. Kada, and L. W. Wattenberg. 1986. Inhibitors of mutagenesis and their relevance to carcinogenesis. Mutat. Res. 168: 47-65.
Rangavajhyala, N., K. M. Shahani, G. Sridevi, and S. Srikumaran. 1997. Nonlipopolysaccharide component(s) of Lactobacillus acidophilus stimulated(s) the production of interleukin-1 αand tumor necrosis facter-α by murin macrophage. Nutr. and Cancer 28(2): 130-134.
Reddy B. S. and A. Rivenson. 1993. Inhibitory effect of Bifidobacterium longum on colon, mammary and liver carcinogenesis induced by 2-amino-3-methylimidazo[4, 5-f]quinoline, afood mutagen. Cancer Res. 53: 3914-3918.
Richard A. G., J. K. Thomas, and A. O. Barbara. 2001. Kuby Immunology. (4 Ed). pp. 46-58. Freeman. USA.
Riku, K., K. Riitta, S. Maija, M. Markku, K. Hannu, and M. Eeva. 2001. Induction of nitric oxide synthesis by probiotic lactobacillus rhamnosus GG in J774 Macrophages and human T84 intestinal epithelial cells. Inflammation 25(4): 223-232.
Rinkus, S. J. and R. T. Taylor. 1990. Analysis of hydrogen peroxide in freshly prepared coffees. Food Chem. Toxicol. 28: 323-331.
Rival S. G., C. G. Boeriu, and H. J. Wichers. 2001. Caseins and casein hydrolysates. 2. andtioxidative properties and relevance to lipoxygenase inhitbition. J. Agric. Food Chem. 49: 295-302.
Robak, J., and I. R. Gryglewski. 1988. Flavonoids are scavengers of superoxide anions. Biochem. Pharmacol. 37: 837-841.
Roshni, M. and K. Ashok. 2002. Role of reactive nitrogen intermediates and protein nitration during immune response against a rat histioxytoma. Immunol. Lett. 84: 145-151.
Ruch R. J., S. J. Cheng, and J. E. Klauning. 1989. Prevention of cytotoxicity and inhibition of intercellular communication by antioxidant catechins isolated from Chinese green tea. Carcinogenesis 10: 1003-1008.
Sandline, W. 1979. Roles of Lactobacillus in the intestinal tract. J. Food Prot. 42: 256-262.
Sarem, F., L. O. Sarem-damerdji, and J. P. Nicolas. 1996. Comparison of the adherence of three Lactobacillus strains to Caco-2 and Int-407 human intestinal cell lines. Lett. Appl. Microbiol. 22: 439-442.
Saucier, L., M. Julien, F. Cheour, R. Ketarte, and J. Goulet. 1992. Effect of feeding lactic acid bacteria and fermented milk on specific and nonspecific immune reponses of mice infected with Klebsiella pneumoniae AD-1. J. Food Prot. 55: 595-600.
Saul, R. L. and B. N. Ames. 1986. Background levels of DNA damage in the papulation. Basic. Life Sci. 38: 529-535.
Savage, D. C. 1983. Mechanisms by which indigenous microorganism colonize cultured milk in lactose-deficiency individuals. Am. J. Clin. Nutr. 39: 756-761.
Savaino, D. A., A. Abauelanor, D. E. Smith, and M. D. Levitt. 1984. Lactose Malabo sorption from yogurt, pasteurized yogurt, sweet acidophilus milk, and cultured milk in lactose-deficiency individuals. Am. J. Clin. Nutr. 39: 756-761.
Schmidt, H. H. H. W. and U. Walter. 1994. NO at work. Cell 78: 919-925.
Scott, V. N. and S. L. Taylor. 1981. Effect of nisin on the out growth of Clostridium botulinum. J. Food Sci. 46: 117-121.
Seth A. and R. R. Mahoney. 2000. Iron chelation by digests of insoluble chichen muscle protein: the role of histidine residues. J. Sci. Food. Agric. 81: 183-187.
Shahidi, F. and P. K. J. P. D. Wanasundara. 1992. Phenolic antioxidants. Crit. Rev. Food Sci. Nutr. 32: 67-103.
Shi, X., N. S. Dalal, and A. C. Jain. 1991. Antioxidant behavious of caffine efficient scavenging of hydroxyl radicals. Food Chem. Toxic. 29: 1-6.
Shimada, K., K. Fujikawa, K. Yahara, and T. Nakamura. 1992. Antioxidative properties of xanthean on the autoxidation of sybean oil in cyclodextrin emulsion. J. Agric. Food Chem. 40: 945-948.
Shimamura S., F. Abe, N. Ishibashi, H. Miyakawa, T. Yaeshima, T. Araya, and Tomita, M. 1992. Relation ship between oxygen sensitivity and oxygen metabolism of Bifidobacterium species. J. Dairy Sci. 75: 3296-3306.
Simic, M. G. 1988. Mechanism of inhibition of free-radical processes in mutagenesis and carcinogenesis. Mutat. Res. 202: 377-386.
Snyder, S. H. and D. S. Bredt. 1992. Biological roles of nitric oxide. Sci. Amer. 266: 68-77.
So Y. P., E. J. Geun, T. K. Young, K. J. Hoo, and U. Zeynep. 1999. Potentiation of hydrogen peroxide, nitric oxide, and cytokine production in RAW 264.7 macrophage cells exposed to human and commercial isolates of Bifidobacterium. Int. J. of Food Microbiol. 46: 231-241.
Stadtman, E. R. and D. N. Oliver. 1991. Metal-catalyzed oxidation of proteins. Physiological consequences. J. Biol. Chem. 266: 2005-2008.
Suetsuna K., H. Ukeda, and H. Ochi. 2000. Isolation and characterization of free radical scavenging acivities pepetides derived from casein. J. Nutr. Biochem. 11:128-131.
Tagg, T. R., A. S. Dajani, and L. W. Wannamaker. 1976. Bacteriocins of Gram-positive bacteria. Bacteriol. Rev. 40: 722-756.
Tamura, Z. 1983. Nurtiology of Bifidobacteria. Bifidobact. Microflora 2: 3.
Tannock, G. W. 1997. Probiotic properties of lactic acid bacteria: plenty of scope for fundamental R and D. Tibtech. 6(15):270-274.
Tong S. S., D. J. Mcclements, and E. A. Decker. 2000. Antioxidant activity of whey in a salmon oil emulsion. Food Chem. Tixicol. 65(8): 1325-1329.
Tubaro, A., C. Florio, E. Luxich, R. Vertua, L. R. Della, and T. Yasumoto. 1996. Suitability of the MTT-based cytotoxicity assay to detect okadaic acid contamination of mussels. Toxicon. 34(9): 965-974.
Underdown, B. J. 1986. Immunoglobulin A, strategic defense initiative at the mucosal surgace. Annu. Rev. Immunol. 4, 389-417.
Vesa, T. H., P. R. Marteau, F. B. Breat, M. C. Boutron-Ruault, and J. C. Rambaud. 1997. Raising milk energy content retards gastric emptying of lactose in lactose-intolerant humans with little effect on lactose digestion. J. Nutr. 127: 2316-2320.
Vinderola, C. G., G. A. Costa, S. Regenhardt, and J. A. Reinheimer. 2002. Influence of compounds associated with fermented dairy products on the growth of lactic acid starter and probiotic bacteria. Int. Dairy J. 12: 579-589.
Wade A. M. and H. N. Tucker. 1998. Antioxidant characteristics of L-histidine. J. Nutr. Biochem. 9: 308-315.
Yamaguchi N., Y. Yokoo, and M. Fujimaki 1975. Studies on antioxidative activities of amino compounds on fats and oils. Nippon Shokuhin Kogyo Gakkaishi 22(9): 425-435.
Yamaguchi, N. and Y. Okada. 1968. Browning reaction products produced by the reaction between sugars and amino acids. VII. Decomposition of lipid hydroperoxide by the browning products. Nippon Shokuhin Kogyo Gakkaishi 15: 187-191.
Yamaguchi, R., M. A. Tatsumi, K. Kato, and U. yoshimitsu. 1988. Effect of metal salts and fructose on the autoxidation of methyl linoleate in emulsions. Agric. Biol. Chem. 52: 849-850.
Yang, Z. G., C. D. Carter, M. S. Miller, and P. N. Bochsler. 1995. CD14 and tissue factor expression by bacterial lipopolysaccharide-stimulated bovine alveolar macrophages in vitro. Infect. Immun. 63 (1): 51-56.
Yasui, H. and M. Ohwaki. 1991. Enhancement of immune response in peyer’s patch cells cultures with Bifidobacterium breve. J. Dairy Sci. 74: 1187-1195.
Yasui, H., Kiyoshima, J., and Ushijima, H. 1995. Passive protection against rotavirus-induced diarrhea of mouse pups born to and nursed by dams fed Bifidobacterium breve YIT4064. J. Inf. Dis. 172(2): 403-409.
Yasui, H., N. Nagaoka, A.Mike, K. Hayakawa, M. Ohwaki. 1992. Detection of Bifidobacterium strains that induce large quantities of IgA. Microbiol. Eol. Health Dis. 5: 155-162.
Zastawny, T. H., M. Dabrowska, T. Jaskolski, M. Klimarczyk, L. Kulinski, A. Koszela, M. Szczeniewicz, M. Sliwinska, P. Witkowski, and R. Olinski. 1998. Comparison of oxidative base damage in mitochondrial and nuclear DNA. Free Radic Biol. Med. 24: 722-725.
Zhang X. B. and Y. Ohta. 1991. Binding of mutagens by fractions of the cell wall skeleton of lactic acid bacteria. J. Dairy Sci. 74: 1477-1481.
Zommara M. A. 2002. In vitro studies on the antioxidant effect of zabady microflora. Egyptian J. Dairy Sci. 3:53-61.
Zommara M., N. Tachibana, M. Sakono, Y. Suzuki, T. Oha, H. Hashiba, and K. Imaizumi. 1996. Whey from cultured skim milk decreases serum cholesterol and increases antioxidant enzymes in liver and red blood cells in rats. Nutr. Res. 16: 293-302.