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苯并[a]芘在双灌注人胎盘灌注模型中的转运:灌注介质中白蛋白的影响。

Transport of benzo[alpha]pyrene in the dually perfused human placenta perfusion model: effect of albumin in the perfusion medium.

作者信息

Mathiesen Line, Rytting Erik, Mose Tina, Knudsen Lisbeth E

机构信息

Institute of Public Health, University of Copenhagen, Copenhagen K, Denmark.

出版信息

Basic Clin Pharmacol Toxicol. 2009 Sep;105(3):181-7. doi: 10.1111/j.1742-7843.2009.00431.x. Epub 2009 Jun 5.

Abstract

Transport of benzo[alpha]pyrene (BaP) across the placenta was examined because it is a ubiquitous and highly carcinogenic substance found in tobacco smoke, polluted air and certain foods. Foetal exposure to this substance is highly relevant but is difficult to estimate. The human placenta is unique compared to other species; since it is available without major ethical obstacles, we have used the human placenta perfusion model to study transport from mother to foetus. Placentas were donated after births at Rigshospitalet in Copenhagen from pregnant mothers who signed an informed consent. BaP is lipophilic and studies using cell culture medium in 6-hr placenta perfusions showed minimal transport through the placenta. To increase the solubility of BaP in perfusion medium and to increase physiological relevance, perfusions were also performed with albumin added to the perfusion medium [2 and 30 mg/ml bovine serum albumin (BSA) and 30 mg/ml human serum albumin (HSA)]. The addition of albumin resulted in increased transfer of BaP from maternal to foetal reservoirs. The transfer was even higher in the presence of an HSA formulation containing acetyltryptophanate and caprylate, resulting in a foetal-maternal concentration (FM) ratio of 0.71 +/- 0.10 after 3 hr and 0.78 +/- 0.11 after 6 hr, whereas the FM ratio in perfusions without albumin was only 0.05 +/- 0.03 after 6 hr of perfusion. Less BaP accumulated in placental tissue in perfusions with added albumin. This shows that transplacental transport of the pro-carcinogenic substance BaP occurs, and emphasizes the importance of adding physiological concentrations of albumin when studying the transport of lipophilic substances.

摘要

对苯并[a]芘(BaP)的胎盘转运进行了研究,因为它是一种普遍存在且具有高度致癌性的物质,存在于烟草烟雾、污染空气中以及某些食物中。胎儿接触该物质具有高度相关性,但难以估计。与其他物种相比,人类胎盘具有独特性;由于获取人类胎盘不存在重大伦理障碍,我们使用人类胎盘灌注模型来研究从母体到胎儿的转运。胎盘由哥本哈根里格霍斯医院分娩后的孕妇捐赠,这些孕妇签署了知情同意书。BaP具有亲脂性,在6小时的胎盘灌注实验中,使用细胞培养基进行的研究显示其透过胎盘的转运极少。为了提高BaP在灌注培养基中的溶解度并增加生理相关性,还在灌注培养基中添加了白蛋白[2和30mg/ml牛血清白蛋白(BSA)以及30mg/ml人血清白蛋白(HSA)]进行灌注。白蛋白的添加导致BaP从母体储库向胎儿储库的转运增加。在含有乙酰色氨酸盐和辛酸盐的HSA制剂存在的情况下,转运甚至更高,3小时后胎儿-母体浓度(FM)比为0.71±0.10,6小时后为0.78±0.11,而在无白蛋白的灌注中,灌注6小时后FM比仅为0.05±0.03。在添加白蛋白的灌注中,胎盘组织中积累的BaP较少。这表明致癌前体物质BaP发生了经胎盘转运,并强调了在研究亲脂性物质转运时添加生理浓度白蛋白的重要性。

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