Toxic effects of triptolide on adrenal steroidogenesis in H295R cells and female rats
Toxic effects of triptolide on adrenal steroidogenesis in H295R cells and female rats
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雷公藤内酯醇对 H295R 细胞和雌性大鼠肾上腺类固醇生成的毒性作用
DOI：
10.1002/jbt.22394
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发表时间：
2019-11
影响因子：
3.6
通讯作者：
Huang Xin
中科院分区：
文献类型：
--
作者：
Xu Lingyan;Wu Wei;Cheng Rui;Sun Lixin;Jiang Zhenzhou;Zhang Luyong;Zhang Zunjian;Su Yuwen;Huang Xin
雷公藤内酯醇（Triptolide，TP）是雷公藤（Tripterygium wilfordii）的主要活性成分，对类风湿性关节炎有较强的免疫抑制作用，但由于其具有多器官毒性，尤其是肝、肾和生殖毒性，临床应用较少。采用LC-MS/MS方法探索TP的内分泌干扰作用。首先使用体外模型（H295 R细胞系）研究了不同浓度（0 - 100 nM）TP持续48小时的内分泌干扰作用。结果发现，TP没有降低细胞活力。通过定量真实的时间聚合酶链反应评估H295 R细胞中类固醇生成酶的转录水平。还探索了TP（0、50和500 μg/kg）经口给药28天对正常和胶原诱导的关节炎（CIA）大鼠可能的肾上腺和内分泌影响。结果表明，TP能显著降低正常和CIA大鼠H295 R细胞内皮质醇水平和血浆皮质酮水平。在500 μg/kg剂量下观察到肾上腺皮质的组织学改变。TP作用48 h后，对皮质类固醇合成所必需的代谢酶-HSD 3B 2、CYP 21 A2、CYP 17 A1和CYP 11B 1的mRNA转录水平有明显的抑制作用。总之，TP导致皮质类固醇合成和分泌紊乱，皮质类固醇可能是TP多器官毒性治疗的潜在生物标志物。
Triptolide (TP), a major active ingredient of Tripterygium wilfordii, exerts potent immunosuppressive effects in the treatment of rheumatoid arthritis but is not widely used in clinical practice due to its multiorgan toxicity, particularly hepatotoxicity, nephrotoxicity, and reproductive toxicity. An LC‐MS/MS approach was employed to explore the endocrine‐disrupting effects of TP. The endocrine‐disrupting effects of various concentrations (0‐100 nM) of TP for 48 hour were firstly investigated using an in vitro model (H295R cell line). It was found that TP did not decrease cell viability. The transcriptional levels of steroidogenic enzymes in H295R cells were assessed by quantificational real‐time polymerase chain reaction. The possible adrenal and endocrine effects of oral administration of TP (0, 50, and 500 μg/kg) for 28 days on both normal and collagen‐induced arthritis (CIA) rats were also explored. The serum and adrenal tissue hormone levels (corticosterone and progesterone) and adrenal histopathology were analyzed, with the results that TP significantly decreased the level of cortisol in H295R cells and the level of plasma corticosterone in both normal and CIA rats. Histological alterations in adrenal cortex were observed at the dose of 500 μg/kg. Exposure to TP for 48 hour had an obvious inhibitory effect on the messenger RNA transcript levels of HSD3B2, CYP21A2, CYP17A1, and CYP11B1, which is essential for the synthesis of corticosteroids. In a word, TP leads to the disorder of corticosteroid synthesis and secretion, and corticosteroid may be a potential biomarker for the treatment of multiorgan toxicity of TP.
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DOI：
10.1155/2018/6409389
发表时间：
2018
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
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作者：
Zhang K;Zhou S;Wang C;Xu H;Zhang L
通讯作者：
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影响因子：
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作者：
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DOI：
10.1007/978-1-4939-2895-8_9
发表时间：
2015-01-01
期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
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DOI：
10.1002/ar.22479
发表时间：
2012-06-01
影响因子：
2
作者：
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通讯作者：
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