Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky 40202, United States.
Chem Res Toxicol. 2011 Jun 20;24(6):877-86. doi: 10.1021/tx2000625. Epub 2011 May 31.
The polyphenolics in green tea are believed to be the bioactive components. However, poor bioavailability following ingestion limits their efficacy in vivo. In this study, polyphenon E (poly E), a standardized green tea extract, was administered by sustained-release polycaprolactone implants (two, 2-cm implants; 20% drug load) grafted subcutaneously or via drinking water (0.8% w/v) to female S/D rats. Animals were treated with continuous low dose of benzo[a]pyrene (BP) via subcutaneous polymeric implants (2 cm; 10% load) and euthanized after 1 and 4 weeks. Analysis of lung DNA by (32)P-postlabeling resulted in a statistically significant reduction (50%; p = 0.023) of BP-induced DNA adducts in the implant group; however, only a modest (34%) but statistically insignificant reduction occurred in the drinking water group at 1 week. The implant delivery system also showed significant reduction (35%; p = 0.044) of the known BP diolepoxide-derived DNA adduct after 4 weeks. Notably, the total dose of poly E administered was >100-fold lower in the implant group than the drinking water group (15.7 versus 1,632 mg, respectively). Analysis of selected phase I, phase II, and nucleotide excision repair enzymes at both mRNA and protein levels showed no significant modulation by poly E, suggesting that the reduction in the BP-induced DNA adducts occurred presumably due to known scavenging of the antidiolepoxide of BP by the poly E catechins. In conclusion, our study demonstrated that sustained systemic delivery of poly E significantly reduced BP-induced DNA adducts in spite of its poor bioavailability following oral administration.
绿茶中的多酚类被认为是具有生物活性的成分。然而，摄入后其生物利用度差限制了它们在体内的功效。在这项研究中，儿茶素多酚 E（多 E），一种标准化的绿茶提取物，通过皮下植入的聚己内酯缓释植入物（两个 2 厘米的植入物；20%的药物负载）或通过饮用水（0.8%w/v）给予雌性 S/D 大鼠。动物通过皮下聚合物植入物（2 厘米；10%负载）持续低剂量给予苯并[a]芘（BP），并在 1 和 4 周后处死。通过（32）P-后标记对肺 DNA 的分析导致植入组 BP 诱导的 DNA 加合物显著减少（50%；p=0.023）；然而，在饮水组中仅发生适度（34%）但无统计学意义的减少在 1 周时。植入物输送系统还显示在 4 周后已知的 BP 二环氧物衍生的 DNA 加合物显著减少（35%；p=0.044）。值得注意的是，植入组给予的多 E 总剂量比饮水组低 100 多倍（分别为 15.7 与 1632 毫克）。在 mRNA 和蛋白质水平上对所选的 I 相、II 相和核苷酸切除修复酶进行分析，表明多 E 没有显著调节，这表明 BP 诱导的 DNA 加合物的减少可能是由于多 E 儿茶素对 BP 的抗二环氧物的已知清除作用所致。总之，我们的研究表明，尽管多 E 经口服后生物利用度差，但持续的系统给予多 E 可显著减少 BP 诱导的 DNA 加合物。
