Synthetic Phenolic Antioxidants Cause Perturbation in Steroidogenesis in Vitro and in Vivo
Synthetic Phenolic Antioxidants Cause Perturbation in Steroidogenesis in Vitro and in Vivo
复制标题
合成酚类抗氧化剂会扰乱体外和体内类固醇生成
DOI：
10.1021/acs.est.7b05057
复制
发表时间：
2018-01-16
影响因子：
11.4
通讯作者：
Jiang, Guibin
中科院分区：
文献类型：
--
作者：
Yang, Xiaoxi;Song, Wenting;Jiang, Guibin
合成酚类抗氧化剂（SPAs）因其广泛的用途与人类生活密切相关，其生物安全性日益受到关注。先前有争议的发现引起了对其潜在内分泌干扰作用的持续争论。本文研究了四种常用的SPA，包括丁基羟基茴香醚（BHA）、丁基羟基甲苯（BHT）、叔丁基对苯二酚（TBHQ）和2，2 '-亚甲基双（6-叔丁基-4-甲基苯酚）（AO 2246）的雌激素样作用。然而，在H295 R中观察到E-2分泌的显著增加。用SPA处理的细胞，特别是BHA。蛋白激酶A（PKA）信号通路介导星星、3 β HSD、CYP 11B 1和CYP 11B 2等类固醇生成酶的转录水平上调。体内实验证实，水中暴露BHA可干扰斑马鱼性腺中的E2和睾酮（T）水平，从而通过调节下丘脑-垂体性腺-肝轴（HPGL-axis）产生潜在的雌激素效应。因此，本研究为研究SPA的内分泌干扰效应提供了新的思路。考虑到食物中单个BHA或与TBHQ和BHT组合的允许最大水平（200 mg kg（-1）），在相对低浓度的SPA中观察到的类固醇生成扰动需要更多的公众关注。
Synthetic phenolic antioxidants (SPAs) are closely correlated with human life due to their extensive usages, and increasing concerns have been raised on their biosafety. The previous controversial findings caused continuous debates on their potential endocrine disrupting effects. In the present study, four commonly used SPAs, including butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tert-butyl hydroquinone (TBHQ) and 2,2'-methylenebis(6-tert-butyl-4-methylphenol) (AO2246), were investigated for their estrogenic effects, and the results from in vitro screening assays showed SPAs themselves had negligible estrogen receptor binding affinities. Nevertheless, significant increase in E-2 secretion was observed in H295R. cells treated with SPAs, especially for BHA. The transcriptional levels of steroidogenic enzymes, including StAR, 3 beta HSD, CYP11B1, and CYP11B2 were up-regulated via the mediation of protein kinase A (PKA) signaling pathway. In vivo experiment confirmed that waterborne exposure to BHA disturbed E2 and testosterone (T) levels in zebrafish gonad, thus causing potential estrogenic effects through the regulation of hypothalamic-pituitary gonadal-liver axis (HPGL-axis). Accordingly, this study has provided new insights for SPA-induced endocrine disrupting effects. Considering the allowable maximum level of individual BHA or in combination with TBHQ and BHT in foodstuffs (200 mg kg(-1)), the perturbation in steroidogenesis observed for relatively low concentrations of SPAs would need more public attention.