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六氯萘(HxCN)对雌性大鼠的潜在内分泌干扰作用。

Hexachloronaphthalene (HxCN) as a potential endocrine disruptor in female rats.

机构信息

Department of Toxicology, Faculty of Pharmacy, Medical University, Muszynskiego 1, 90-151, Lodz, Poland.

出版信息

Environ Pollut. 2018 Dec;243(Pt B):1026-1035. doi: 10.1016/j.envpol.2018.09.045. Epub 2018 Sep 17.

DOI:10.1016/j.envpol.2018.09.045
PMID:30253293
Abstract

Hexachloronaphthalene (HxCN) is one of the most toxic and most bioaccumulative congeners of polychlorinated naphthalenes (PCNs) known to be present in animal and human adipose tissue. Unfortunately, little data is available regarding the negative effect of PCNs on endocrine function. The aim of the study was to investigate the direct influence of subacute (two and four-week) and subchronic (13-week) daily oral exposure of female rats to 30, 100 and 300 μg kg b.w. HxCN on ovarian, thyroid function and neurotransmitters level. The levels of selected sex hormones (progesterone: P and estradiol: E2) in the serum and uterus, regularity of estrous cycle, levels of thyroid hormones (fT3 and fT4), TSH, γ-aminobutyric acid and glutamate levels in selected brain areas and the activity of CYP1A1 and CYP2B in the liver were examined. Estrogenic action (elevated E2 concentration in the uterus and serum) was observed only after subacute exposure, and antiestrogenic activity (decreased E2 level and uterus weight) after 13 weeks administration of 300 μg kg b.w. day. Subchronic administration of HxCN significantly lengthens the estrous cycle, by up to almost 50%, and increases the number of irregular cycles. In addition, increased TSH and decreased fT4 serum levels were observed after all doses and durations of exposure to HxCN. Only subacute exposure led to a significant decrease in the level of examined neurotransmitters in all analyzed structures. Additionally, exposure to low doses of HxCN appears to lead to strong induction of CYP1A1 in a liver. It can be hypothesized that HxCN produces effects which are very similar to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dioxin-like compounds (DLCs), particularly concerning endocrine and estrous cyclicity disorders. Therefore, HxCN exposure may exert unexpected effects on female fecundity among the general population.

摘要

六氯萘(HxCN)是多氯萘(PCN)中最具毒性和生物累积性的同系物之一,存在于动物和人体脂肪组织中。不幸的是,关于 PCN 对内分泌功能的负面影响,数据很少。本研究的目的是调查雌性大鼠亚急性(两周和四周)和亚慢性(十三周)每日口服暴露于 30、100 和 300μg/kg b.w. HxCN 对卵巢、甲状腺功能和神经递质水平的直接影响。血清和子宫中选定的性激素(孕酮:P 和雌二醇:E2)水平、发情周期的规律性、甲状腺激素(fT3 和 fT4)、TSH、γ-氨基丁酸和谷氨酸水平在选定的大脑区域和 CYP1A1 和 CYP2B 在肝脏中的活性进行了检查。只有在亚急性暴露后才观察到雌激素作用(子宫和血清中 E2 浓度升高),而在 300μg/kg b.w. 天的 13 周给药后观察到抗雌激素作用(E2 水平和子宫重量降低)。HxCN 的亚慢性给药显著延长发情周期,最长可达近 50%,并增加不规则周期的数量。此外,在所有剂量和暴露时间下,HxCN 暴露后观察到 TSH 增加和 fT4 血清水平降低。只有亚急性暴露导致所有分析结构中检查神经递质水平显著降低。此外,低剂量 HxCN 暴露似乎导致肝脏中 CYP1A1 的强烈诱导。可以假设 HxCN 产生的作用与 2,3,7,8-四氯二苯并对二恶英(TCDD)和类二恶英化合物(DLCs)非常相似,特别是关于内分泌和发情周期紊乱。因此,HxCN 暴露可能会对普通人群中的女性生育能力产生意想不到的影响。

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