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大鼠体内多种成分暴露过程中的性别差异。

Sex Differences in the In Vivo Exposure Process of Multiple Components of in Rats.

作者信息

Zuo Meng-Ting, Gong Meng-Die, Ma Xiao, Xu Wen-Bo, Wang Zi-Yuan, Tang Mo-Huan, Wu Yong, Liu Zhao-Ying

机构信息

College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China.

Hunan Engineering Technology Research Center of Veterinary Drugs, Hunan Agricultural University, Changsha 410128, China.

出版信息

Metabolites. 2022 Dec 24;13(1):33. doi: 10.3390/metabo13010033.

DOI:10.3390/metabo13010033
PMID:36676958
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9865510/
Abstract

Asian () has a wide range of pharmacological activities. However, its strong toxicity limits its potential development and application. Interestingly, there are significant gender differences in toxicity in rats. This work aimed to elucidate the overall absorption, distribution, metabolism, and excretion (ADME) of whole crude extract in female and male rats using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS), which facilitates determining the reasons for the gender differences in toxicity. A total of 25 absorbed bioactive components and 3 related produced metabolites were tentatively identified in female rats, while only 17 absorbed bioactive components and 3 related produced metabolites were identified in male rats. By comparison of peak intensities, most compounds were found to be more active in absorption, distribution and excretion in female rats than in male rats, which showed that female rats were more sensitive to . This study was the first to investigate the multicomponent in vivo process of in rats and compare the differences between sexes. It was hypothesized that differences in the absorption of gelsedine-type alkaloids were one of the main reasons for the sex differences in toxicity.

摘要

亚洲(某种物质)具有广泛的药理活性。然而,其强毒性限制了其潜在的开发和应用。有趣的是,在大鼠中该物质的毒性存在显著的性别差异。这项工作旨在使用高效液相色谱-四极杆飞行时间质谱联用技术(HPLC/QqTOF-MS)阐明雌性和雄性大鼠中整个(该物质)粗提取物的整体吸收、分布、代谢和排泄(ADME)情况,这有助于确定毒性性别差异的原因。在雌性大鼠中初步鉴定出总共25种吸收的生物活性成分和3种相关产生的代谢物,而在雄性大鼠中仅鉴定出17种吸收的生物活性成分和3种相关产生的代谢物。通过峰强度比较,发现大多数化合物在雌性大鼠中的吸收、分布和排泄比在雄性大鼠中更活跃,这表明雌性大鼠对(该物质)更敏感。本研究首次研究了(该物质)在大鼠体内的多成分过程并比较了性别差异。据推测,格赛丁型生物碱吸收的差异是(该物质)毒性性别差异的主要原因之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a7c/9865510/a422b725f0d8/metabolites-13-00033-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a7c/9865510/3bb393e1cb7a/metabolites-13-00033-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a7c/9865510/845a6f321ba9/metabolites-13-00033-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a7c/9865510/a422b725f0d8/metabolites-13-00033-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a7c/9865510/3bb393e1cb7a/metabolites-13-00033-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a7c/9865510/845a6f321ba9/metabolites-13-00033-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a7c/9865510/a422b725f0d8/metabolites-13-00033-g003.jpg

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2
Toxicokinetics, in vivo metabolic profiling, and in vitro metabolism of gelsenicine in rats.在体毒代动力学、体内代谢物谱分析及大鼠体内格尔森辛的体外代谢。
Arch Toxicol. 2022 Feb;96(2):525-533. doi: 10.1007/s00204-021-03209-7. Epub 2022 Jan 23.
3
Toxicity assessment of gelsenicine and the search for effective antidotes.银杏宁的毒性评估与有效解毒剂的寻找。
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271211062857. doi: 10.1177/09603271211062857.
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Metabolic profile and tissue distribution of Humantenirine, an oxindole alkaloid from Gelsemium, after oral administration in rats.钩吻中一种氧化吲哚生物碱——胡蔓藤碱乙在大鼠口服给药后的代谢概况及组织分布
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Phosphoproteomics reveals NMDA receptor-mediated excitotoxicity as a key signaling pathway in the toxicity of gelsenicine.磷酸化蛋白质组学揭示 NMDA 受体介导的兴奋性毒性是高乌甲素毒性的关键信号通路。
Food Chem Toxicol. 2021 Oct;156:112507. doi: 10.1016/j.fct.2021.112507. Epub 2021 Aug 11.
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Homeopathic Remedies in COVID-19: Prognostic Factor Research.顺势疗法药物在COVID-19中的应用:预后因素研究。
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