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[大鼠血液中羟基化多氯二苯并呋喃代谢物潴留的初步研究]

[Preliminary studies on the retention of hydroxylated PCDF metabolites in rat blood].

作者信息

Kuroki H, Ishimura N, Masuda Y, Klasson-Wehler E, Bergman A

机构信息

Daiichi College of Pharmaceutical Sciences, Fukuoka.

出版信息

Fukuoka Igaku Zasshi. 1995 May;86(5):169-77.

PMID:7628804
Abstract

We recently reported that certain hydroxylated PCB (OH-CB) metabolites were selectively retained in blood of rats experimentally dosed with PCB (Aroclor 1254), and also in blood of seals and humans environmentally exposed to PCBs. We also showed that metabolism in vivo of polychlorinated dibenzofurans (PCDFs) gave rise to a large number of hydroxylated PCDF (OH-CDF) metabolites, excreted in faeces, after oral administration to rats of PCDFs mixture (1, 2, 7, 8-tetraCDF 14%, 2, 3, 7, 8-tetraCDF 35%, 1, 2, 3, 7, 8-pentaCDF 48%). These results suggest that OH-CDFs could be present in blood. In the present study, potential retention of OH-CDF metabolites in blood (serum) was investigated in a female Wistar rat exposed to the PCDFs mixture. Serum was analyzed for the methylated OH-CDFs by gas chromatography (GC) and GC-mass spectrometry. Two major metabolites were determined in serum 1 day after oral administration. These were identified to be 3-OH-2, 4, 7, 8-tetraCDF (A) and 3-OH-2, 4, 7, 8, 9-pentaCDF (B) by comparison with synthesized reference compounds. 3-OH-2, 4, 7, 8-tetraCDF and 1, 2, 3, 7, 8-pentaCDF, respectively, via 3, 4(6, 7)-epoxide intermediate and subsequent NIH-shift of the 3(7)-chlorine to the 4(6)-position. The amounts of 3-OH-2, 4, 7, 8-tetraCDF and 3-OH-2, 4, 7, 8, 9-pentaCDF in the serum (5.72 g) analyzed accounted for 0.018% of 2, 3, 7, 8-tetraCDF and 0.003% of 1, 2, 3, 7, 8-pentaCDF dosed, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

我们最近报道,某些羟基化多氯联苯(OH-CB)代谢物在实验性给予多氯联苯(Aroclor 1254)的大鼠血液中被选择性保留,在海豹和环境中接触多氯联苯的人类血液中也有发现。我们还表明,多氯二苯并呋喃(PCDFs)在体内的代谢会产生大量羟基化多氯二苯并呋喃(OH-CDF)代谢物,在给大鼠口服PCDFs混合物(1,2,7,8-四氯二苯并呋喃14%,2,3,7,8-四氯二苯并呋喃35%,1,2,3,7,8-五氯二苯并呋喃48%)后经粪便排出。这些结果表明OH-CDFs可能存在于血液中。在本研究中,对一只暴露于PCDFs混合物的雌性Wistar大鼠血液(血清)中OH-CDF代谢物的潜在保留情况进行了研究。通过气相色谱(GC)和GC-质谱法分析血清中的甲基化OH-CDFs。口服给药1天后在血清中检测到两种主要代谢物。通过与合成参考化合物比较,确定它们分别为3-羟基-2,4,7,8-四氯二苯并呋喃(A)和3-羟基-2,4,7,8,9-五氯二苯并呋喃(B)。3-羟基-2,4,7,8-四氯二苯并呋喃和1,2,3,7,8-五氯二苯并呋喃分别通过3,4(6,7)-环氧化物中间体以及随后3(7)-氯向4(6)-位的NIH重排产生。所分析的血清(5.72微克)中3-羟基-2,4,7,8-四氯二苯并呋喃和3-羟基-2,4,7,8,9-五氯二苯并呋喃的量分别占给药的2,3,7,8-四氯二苯并呋喃的0.018%和1,2,3,7,8-五氯二苯并呋喃的0.003%。(摘要截取自250字)

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