Modulation of human glutathione S-transferases by Polyphenon E intervention
Modulation of human glutathione S-transferases by Polyphenon E intervention
复制标题
DOI：
10.1158/1055-9965.epi-06-0830
复制
发表时间：
2007-08-01
影响因子：
3.8
通讯作者：
Alberts, David S.
中科院分区：
文献类型：
--
作者：
Chow, H.-H. Sherry;Hakim, Iman A.;Alberts, David S.
目的：饮用绿茶与降低人类罹患某些癌症的风险有关。解毒酶的诱导被认为是绿茶预防癌症作用的生化机制之一。我们进行了这项临床研究，以确定反复服用绿茶多酚对一组主要解毒酶，谷胱甘肽s -转移酶（GST）的影响。方法：共有42名健康志愿者通过不喝茶或茶相关产品进行了为期4周的洗脱期。洗脱期结束时，采集空腹血样，分离血浆和淋巴细胞，评估GST活性和水平。在基线评估之后，研究参与者接受了4周的绿茶多酚干预，以标准多酚E制剂的形式，剂量包含800毫克表没食子儿茶素没食子酸酯（EGCG），每天一次。空腹服用多酚E以优化EGCG的口服生物利用度。干预完成后，收集样本进行干预后的商品及服务税评估。结果：4周多酚E干预使外周血淋巴细胞GST活性由30.7 +/- 12.2提高到35.1 +/- 14.3 nmol/min/mg蛋白，P = 0.058；基于基线活性的分析显示，在最低五分之一的个体中，GST活性有统计学意义上的增加（80%,P = 0.004），而在最高五分之一的个体中，GST活性有统计学意义上的降低（20%,P = 0.02）。此外，Polyphenon E干预显著提高了血淋巴细胞GST-pi水平，从2252.9 +/- 734.2增加到2634.4 +/- 1138.3 ng/mg蛋白，P = 0.035。基于基线水平的分析显示，这种增加仅在最低分位数的基线水平个体中显著（P = 0.003），平均增加80%。反复给药多酚E对淋巴细胞GST-mu和血浆gst - α水平影响最小。血浆gst - α水平在最高五分位数中有较小但有统计学意义的下降（8%,P = 0.003）。结论：我们得出结论，在基线酶活性/水平的基础上，4周多酚E给药对GST活性和GST-pi水平有不同的影响，基线酶活性/水平低的个体GST活性和GST-pi水平显著升高。这表明绿茶多酚干预可能会提高低基线解毒能力个体对致癌物的解毒能力。
Purpose: Green tea consumption has been associated with decreased risk of certain types of cancers in humans. Induction of detoxification enzymes has been suggested as one of the biochemical mechanisms responsible for the cancer-preventive effect of green tea. We conducted this clinical study to determine the effect of repeated green tea polyphenol administration on a major group of detoxification enzymes, glutathione S-transferases (GST).Methods: A total of 42 healthy volunteers underwent a 4-week washout period by refraining from tea or tea-related products. At the end of the washout period, a fasting blood sample was collected, and plasma and lymphocytes were isolated for assessment of GST activity and level. Following the baseline evaluation, study participants underwent 4 weeks of green tea polyphenol intervention in the form of a standardized Polyphenon E preparation at a dose that contains 800 mg epigallocatechin gallate (EGCG) once a day. Polyphenon E was taken on an empty stomach to optimize the oral bioavailability of EGCG. Upon completion of the intervention, samples were collected for postintervention GST assessment.Results: Four weeks of Polyphenon E intervention enhanced the GST activity in blood lymphocytes from 30.7 +/- 12.2 to 35.1 +/- 14.3 nmol/min/mg protein, P = 0.058. Analysis based on baseline activity showed that a statistically significant increase (80%, P = 0.004) in GST activity was observed in individuals with baseline activity in the lowest tertile, whereas a statistically significant decrease (20%, P = 0.02) in GST activity was observed in the highest tertile. In addition, Polyphenon E intervention significantly increased the GST-pi level in blood lymphocytes from 2,252.9 +/- 734.2 to 2,634.4 +/- 1,138.3 ng/mg protein, P = 0.035. Analysis based on baseline level showed that this increase was only significant (P = 0.003) in individuals with baseline level in the lowest tertile, with a mean increase of 80%. Repeated Polyphenon E administration had minimal effects on lymphocyte GST-mu and plasma GST-alpha levels. There was a small but statistically significant decrease (8%, P = 0.003) in plasma GST-alpha levels in the highest tertile.Conclusions: We conclude that 4 weeks of Polyphenon E administration resulted in differential effects on GST activity and level based on baseline enzyme activity/level, with GST activity and GST-pi level increased significantly in individuals with low baseline enzyme activity/level. This suggests that green tea polyphenol intervention may enhance the detoxification of carcinogens in individuals with low baseline detoxification capacity.