中华猕猴桃的防癌作用 (五)阻断大鼠和健康人体内N-亚硝基脯氨酸的合成

本文报导中华猕猴桃对体内N-2硝基脯氨酸(NPRO)合成的阻断效果。研究对象为15只雄性Wistar大鼠和10名男性健康志愿者。用自身对照分期观察。大鼠实验表明,中华猕猴桃汁可阻断体内NPRO合成(阻断率59.6％),且效果优于同浓度维生素C溶液,志愿者食入150g含75mg维生素C的中华猕猴桃可完全阻断服300mgNaNO_3和500mg脯氨酸后体内的NPRO合成,而75mg维生素C仅部分阻断。     

中华猕猴桃的防癌作用——(六)阻断孕鼠、孕妇体内N-亚硝基脯氨酸合成

本文报导,中华猕猴桃汁阻断孕鼠及孕妇体内N-亚硝基脯氨酸(NPRO)合成作用,并首次报道NPRO可通过胎盘进入胎内。21只孕鼠实验中,在体内合成高量NPRO的同时,胎内检出了NPRO。中华猕猴桃汁可通过阻断NPRO在体内合成从而阻止其进入胎内。27名孕妇观察也见到同样的结果,仅在4名未服猕猴桃汁孕妇的羊水中检出低量NPRO。     

中华猕猴桃汁阻断胃癌高发区人群的内源性N-亚硝基化合物合成

本文以空腹胃液中挥发性亚硝胺(VNA)和24小时尿N-亚硝基脯氨酸(NPRO)排出量为指标,观察中华猕猴桃汁(简称桃汁)阻断胃癌高发区人群内源性N-亚硝基化合物(NOC)合成的阻断作用。受试者服用30ml桃汁后,空腹胃液中VNA总量由平均2.08±1.06μg/L显著下降至0.42±0.43μg/L(P<0.01),阻断率为79.8％。在NPRO试验中,受试验者摄入300mg脯氨酸后,尿NPRO排出量由本底的3.3±1.2μg/d显著升高至9.4±4.7μg/d(P<0.001)。与脯氨酸同时服用30ml桃汁后,NPRO排出量显著降低至本底水平(2.9±1.9μg/d,P<0.001)。上述阻断作用在胃粘膜病变程度不同的三组人群间未见显著性差别(P>0.1)。本研究证实,中华猕猴桃汁能有效地阻断胃癌高危人群内源性NOC合成。     

柿科植物叶对亚硝胺体内外合成的阻断作用

本文研究了柿科植物叶对N-亚硝基脯氨酸(NPRO)体内外合成的阻断作用,从而得出如下结论:每天饮用5～10g多维茶就可阻断人体内源性亚硝基化合物的合成。对N-亚硝化反应起阻断作用的主要成分为还原型抗坏血酸,此外多酚类或其它成分也可能在其中起部分作用。     

中华猕猴桃汁的防癌作用——(二)在体外模拟胃液中对亚硝胺合成的阻断作用—Ames试验方法检测

本文研究了猕猴桃汁对N-二甲基亚硝胺体外合成的阻断作用,以鼠伤寒沙门氏菌致突变试验检验。 将二甲基亚硝胺的前体物质-亚硝酸钠和氨基比林,在体外模拟胃液条件下(pH3.3,37％℃)保温一小时,以鼠伤寒沙门氏菌变异株TA100,按常规方法(平皿掺入试验)检验致突变性。当两种前体浓度达5mg/ml以上时,如不加阻断剂,均显示出突变阳性反应,提示反应体系中形成了有致突变性的亚硝胺。如果同时加入猕猴桃汁,可以阻断亚硝胺合成,在5mg/ml和8mg/ml两个浓度的测定结果均未出现致突变作用。在5mg/ml反应体系中,分别加入桃汁和维生素C溶液进行对比,发现桃汁的阻断效率高于维生素C,每皿菌落数均值分别为252±4.2(桃汁),和445±81.2(同浓度维生素C),两者差异有显著性(P<0.01)。结果证明猕猴桃汁对体外亚硝胺合成的阻断作用优于同浓度的维生素C溶液。同样条件下单独保温的亚硝酸钠氨基比林或磷酸缓冲液均无致突变作用。 同样条件下处理的样品(亚硝酸钠,氨基比林各5mg/ml,加到pH3.3磷酸缓冲液中,37℃混合保温1小时)经水蒸气蒸馏,二氯甲烷萃取,浓缩后用气相色谱—质谱联机分析,确认为N-二甲基亚硝胺(NDMA)。     

大蒜阻断人体内N-亚硝基脯氨酸的合成

本文采用Ohshima以GC-TEA定量测定尿中N-亚硝基脯氨酸排出量的方法,以9名健康志愿者为对象,研究大蒜阻断人体内N-亚硝基脯氨酸的合成。受试者食生大蒜5g能完全阻断300mg硝酸钠与500mgL-脯氨酸在人体内合成N-亚硝基脯氨酸,平均阻断率为114.68％,为人群食大蒜预防内源性N-亚硝基化合物的合成及由此造成的致癌性危害提供科学依据。     

营养学报第10卷主题索引

三划N一亚硝基化合物 ,蔬菜阻断作用,26 四划中华称猴桃 ,防癌作用,阻断N一亚硝基脯氨酸合成,体 内,50 ,阻断孕鼠、孕妇体内N一亚硝基脯氨酸合成, 130 ,阻断N一亚硝基脯氨酸合成,慢性萎缩性胃 炎病人,230牛磺酸 ,人尿中含童与高血压的关系,新疆,6,不溶性膳食纤维 ,谷物和谷物食品测定,360计算机 ,对膳食结构分析和营养状况评价的应用, 1 96 ,油菜花粉的影响,大鼠,258 ,浓缩鱼油对血小板聚集和凝血时间、组织脂 肪酸含量影响,341血浆 ,视黄醉和生育酚测定,HPLC,272亚硝酸盐 ,摄入量,胃癌危险性不同人群,234七划泛酸 ,HPLC测定,婴儿奶粉,…     

中华猕猴桃的防癌作用(三)在模拟人胃液中对N-亚硝酰胺合成的阻断作用——Ames试验

本文用Ames试验的方法研究了中华猕猴桃汁对N-亚硝酰胺体外合成的阻断作用。 在模拟人胃液的条件下,亚硝酸钠和甲基硝基胍能反应生成N-甲基-N′-硝基-N亚硝基胍,在Ames氏平皿掺入试验中引起鼠伤寒沙门氏菌TA100菌株的突变反应,有明显的剂量反应关系。当亚硝酸钠浓度为50mM,甲基硝基胍为100mM时,突变菌落数高达4327个/皿,为自发回变的19.94倍。中华猕猴桃汁能阻断N-甲基-N′-硝基-N-亚硝基胍合成,抑制突变反应。在亚硝酸钠浓度为22.2mM,甲基硝基胍为44.4mM时,猕猴桃汁能完全阻断N-甲基-N′-硝基-N-亚硝基胍的合成,致突变反应为阴性。而不加猕猴桃汁的同浓度反应体系引起的突变反应为自发回变的12.59倍。桃汁组低于此浓度的反应体系结果皆是阴性,而对高于此浓度的反应体系,猕猴桃汁不能完全阻断N-甲基-N′-硝基-N-亚硝基胍合成,但能明显抑制突变反应。对中等浓度的反应体系,与桃汁含量相同的抗坏血酸溶液亦能部分阻断N-甲基-N′-硝基-N-亚硝基胍的合成,但作用低于猕猴桃汁。实验结果证明猕猴桃汁阻断N-甲基-N′-硝基-N-亚硝基胍体外合成的作用明显优于同浓度抗坏血酸溶液。 在相同实验条件下,单独的亚硝酸钠或甲基硝基胍均无致突变作用。经薄层层析方法定性分析,反应生成物是N-甲基-N′-硝基-N-亚硝基胍。     

中华猕猴桃汁中亚硝酸盐清除剂3-羟基-2-吡喃酮的鉴定

过去已证明中国产的中华猕猴桃汁确实能阻断N-亚硝基化合物合成。用酶破坏维生素C(Vc)后,仍有阻断作用,说明除Vc外,还有亚硝酸盐(NO_2~-)的清除剂。本文鉴定过去未曾报道过的另一NO_2~-清除剂3-羟基-2-吡喃酮。猕猴桃汁离心后,用4倍乙醚提取,氮气浓缩,加0.01M甲酸铵,用氮气吹去其余乙醚。用0.01M甲酸铵为流动相,样液进反相高压液相(HPLC),测每峰及峰间洗提液,找出     

中华猕猴桃的防癌作用 (四)浓缩猕猴桃汁阻断N-亚硝酰胺的体内合成——大鼠胚胎毒性实验

在妊娠第7、8、9天经口给孕鼠不同剂量的前体物亚硝酸钠(分别为0.125、0.25、0.50、1.00和2.00mmol/kgBW)和乙基脲(剂量是亚硝酸钠的二倍),同时给浓缩猕猴桃汁或4％淀粉液。不给猕猴桃汁的各组随前体物剂量增大,活胎率下降,吸收胎率逐渐增加,分别为5.21％,43.66％,71.70％,85.80％和100％。最高剂量组胚胎全部死亡,并有半数孕鼠中毒死亡。单给高剂量亚硝酸钠或乙基脲则不引起胚胎或孕鼠死亡。表明亚硝酸钠和乙基脲在大鼠体内合成N-亚硝基乙基脲,并通过胎盘引起胚胎死亡。前体物与胚胎毒性之间有明显的剂量反应关系。同时给孕鼠浓缩猕猴桃汁的各组在亚硝酸钠0.125-0.50mmol/kgBW者胚胎存活率无明显减少,仅最高剂量组活胎率明显减少,吸收胎率达58.6％,但无孕鼠中毒死亡。实验结果表明浓缩猕猴桃汁能明显阻断大鼠体内N-亚硝基乙基脲合成,预防所引起的胚胎毒性。     

Effect of ascorbic acid dose taken with a meal on nitrosoproline excretion in subjects ingesting nitrate and proline

We determined the dose of ascorbic acid (ASC) given to subjects with a standard 400‐calorie meal that inhibited N‐nitrosoproline (NPRO) formation when we gave 400 mg of nitrate one hour before and 500 mg of L‐proline with the standard meal. Volunteers consumed their normal US diets but restricted their intakes of nitrate, proline, NPRO, and ASC. NPRO and N‐nitrososarcosine (NSAR) were determined in the 18‐hour urines by methylation followed by gas chromatography‐thermal energy analysis. Mean NPRO yields were 10.7, 41.9, 33.2, 22.3, and 23.1 nmol for groups of 9–25 subjects taking proline alone, proline + nitrate, and proline + nitrate + 120, 240, and 480 mg of ASC, respectively. There was a significant trend to lower NPRO yields as the ASC dose was raised. These results correspond to inhibitions by ASC of 28%, 62%, and 60%, respectively. Pairwise comparison showed that each group taking ASC formed significantly less NPRO than the group given only proline + nitrate. Mean NSAR yields were 9.0 nmol when proline alone was taken and 16.9–24.0 nmol when proline + nitrate + ASC was taken, with no trend to increase as the ASC dose was raised. However, NPRO and NSAR yields in individual urines were correlated with each other. We concluded that 120 mg of ASC taken with each meal (360 mg/day) would significantly reduce in vivo nitrosamine formation, similar to tests by Leaf and co‐workers (Carcinogenesis 8, 791–795, 1987) in which the reactants were taken between meals. The inhibitory dose of ASC may be <120 mg/meal when doses of nitrate and proline are not taken.     

Consumption of watermelon juice increases plasma concentrations of lycopene and beta-carotene in humans

Watermelon is a rich natural source of lycopene, a carotenoid of great interest because of its antioxidant capacity and potential health benefits. Assessment of bioavailability of lycopene from foods has been limited to tomato products, in which heat processing promotes lycopene bioavailability. We examined the bioavailability of lycopene from fresh-frozen watermelon juice in a 19-wk crossover study. Healthy, nonsmoking adults (36-69 y) completed three 3-wk treatment periods, each with a controlled, weight-maintenance diet. Treatment periods were preceded by "washout" periods of 2-4 wk during which lycopene-rich foods were restricted. All 23 subjects consumed the W-20 (20.1 mg/d lycopene, 2.5 mg/d beta-carotene from watermelon juice) and C-0 treatments (controlled diet, no juice). As a third treatment, subjects consumed either the W-40 (40.2 mg/d lycopene, 5.0 mg/d beta-carotene from watermelon juice, n = 12) or T-20 treatment (18.4 mg/d lycopene, 0.6 mg/d beta-carotene from tomato juice, n = 10). After 3 wk of treatment, plasma lycopene concentrations for the W-20, W-40, T-20 and C-0 treatments were (least squares means +/- SEM) 1078 +/- 106, 1183 +/- 139, 960 +/- 117 and 272 +/- 27 nmol/L, respectively. Plasma concentrations of beta-carotene were significantly greater after W-20 (574 +/- 49 nmol/L) and W-40 (694 +/- 73 nmol/L) treatments than after the C-0 treatment (313 +/- 27 nmol/L). Plasma lycopene concentrations did not differ at wk 3 after W-20, W-40 and T-20 treatments, indicating that lycopene was bioavailable from both fresh-frozen watermelon juice and canned tomato juice, and that a dose-response effect was not apparent in plasma when the watermelon dose was doubled.     

茶叶中影响N-亚硝化反应有效成分的初步探讨

首先通过对茶叶中可能影响N-亚硝化反应的物质(抗坏血酸、茶多酚、茶儿茶素,黄酮)进行测定,并与阻断能力进行简单相关和多元(相关、回归、主成分)分析,结果提示茶叶中以茶多酚作用为最大。而后,进行证实试验。结果:黄山毛峰(绿茶)水提取液2ml的阻断率为88％,2ml水提取液所含抗坏血酸的阻断率为28％,而水提取液中茶多酚阻断率为74％;相应量的茶儿茶素阻断率为75％,茶多酚及茶儿茶素对N-亚硝化反应的作用与茶叶水提取液相似,即高水平抑制,低水平促进。由此可以认为,茶叶中影响N-亚硝化反应的主要成分为茶多酚,尤为茶儿茶素。     

Teas and tea components as inhibitors of carcinogen formation in model systems and man.

BACKGROUND. Epidemiological evidence points to a cancer protective role of green-yellow-orange vegetables and fruits. The involvement of teas as a protective factor in carcinogenesis has not received the attention it seems to merit. To gain relevant information, attempts were made to stimulate in vitro those conditions to which human groups are actually exposed. METHODS. The inhibitory effects of infusions of Chinese, Japanese, and Ceylonese teas were examined by adding them to a nitrosation mixture consisting of 0.8 mg sodium nitrite and 340 mg equivalent of a widely consumed salt-preserved fish (Pak Wik) and estimating the frequency of mutants in TA 1535 strain of Salmonella typhimurium. RESULTS. The tea samples exhibited a strong inhibitory effect at concentrations that are actually ingested by man. A comparable inhibition was obtained by several tea phenolics. A second series of experiments dealt with the formation of nitrosoproline (NPRO) which can be strongly inhibited in vitro by the tea infusions and tea phenolics. The effects of the tea infusions and caffeic acid on the endogeneous formation of NPRO in man were examined by having volunteers ingest 300 mg sodium nitrate and 30 min later 300 mg proline, collecting urine samples over a 24-hr period, and estimating the excreted NPRO. The tested teas, at doses regularly consumed, again exerted a strong inhibitory effect on endogeneous NPRO formation in humans. Comparable inhibitory effects were obtained by ingesting caffeic acid, chlorogenic acid, or ferulic acid with the nitrosation mixture. CONCLUSIONS. These results indicate that the simultaneous intake of teas with food products that are being nitrosated within the stomach of human subjects should exert a protective, beneficial effect.     

Problems with folacin status with use of orange juice substitutes in a geriatric institution

An increased range of orange drinks is now available with varying proportions of orange juice. These have begun to appear in institutions for the care of elderly people. With evidence of folacin deficiency in such elderly people, we evaluated the effect of either 100% orange juice or an orange drink (at least 5% juice) on folacin status in 19 institutionalized elderly people over a 13-week period. Serum folacin increased from 8.5 ± 0.8 to 13.2 ± 0.8 nmol/l ( P < 0.001) in 13 weeks, with 100 ml orange juice daily, but did not change from baseline (8.9 ± 0.8 nmol/l) to 13 weeks (8.5%± 0.7 nmol/l) with orange drink. By 6 weeks the difference between orange juice (11.0 ± 1.0 nmol/l) and orange drink (8.6 ± 0.7 nmol/l) was significant. Thus, not only is the choice of orange drink important, but small regular orange juice supplements can produce a significant increase in biochemical folacin status.     

A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interaction

BACKGROUND: Grapefruit juice (GFJ) enhances the systemic exposure of numerous CYP3A4 drug substrates, including felodipine, by inhibiting intestinal (but not hepatic) first-pass metabolism. Furanocoumarins have been identified as major CYP3A4 inhibitors contained in the juice, but their contribution to the GFJ effect in vivo remains unclear. OBJECTIVE: To ascertain whether furanocoumarins mediate the GFJ-felodipine interaction, a furanocoumarin-free GFJ was created and tested against orange juice and the original GFJ with respect to the oral pharmacokinetics of felodipine. DESIGN: With the use of food-grade solvents and absorption resins, furanocoumarins were removed (approximately 99%) from whole GFJ, whereas other major ingredients (flavonoids) were retained. In an open, 3-way, randomized crossover design, 18 healthy volunteers ingested felodipine (10 mg) with 1 of the 3 juices (240 mL). Blood was collected over 24 h. At least 1 wk elapsed between juice treatments. RESULTS: The median and range of the area under the curve and the maximum concentration of felodipine were significantly (P < 0.001) greater with consumption of GFJ [110 (range: 58-270) nmol . h/L and 21 (7.6-50) nmol/L, respectively] than with that of orange juice [54 (29-150) nmol . h/L and 7.6 (3.4-13.9) nmol/L, respectively] or furanocoumarin-free GFJ [48 (23-120) nmol . h/L and 8.3 (3.0-16.6) nmol/L, respectively]. GFJ, orange juice, and furanocoumarin-free GFJ did not differ significantly (P > 0.09) in median time to reach maximum plasma concentration [2.5 (1.5-6), 2.8 (1.5-4), and 2.5 (2-6) h, respectively] or terminal half-life [6.6 (4.2-13.6), 7.8 (4.4-13.2), and 6.8 (2.6-14.4) h, respectively]. CONCLUSION: Furanocoumarins are the active ingredients in GFJ responsible for enhancing the systemic exposure of felodipine and probably other CYP3A4 substrates that undergo extensive intestinal first-pass metabolism.