应用比较毒理基因组学数据库解析尼泊金酯毒理学通路
Searching for Toxic Pathways of Parabens Using the Comparative Toxicogenomics Database
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摘要: 尼泊金酯被广泛用于化妆品、食品以及药物保存的防腐剂，其对生态和人类健康的影响备受关注。目前，比较毒理基因组学数据库已发展成为重要的毒理信息学资源。因此，本研究应用该数据库，通过手动策划，分析了5种常见尼泊金酯影响的潜在基因和通路。结果表明，尼泊金酯共同影响基因主要是雌激素受体以及与脂代谢相关基因；核受体机制，特别是对雌激素受体的干扰作用可能是所有尼泊金酯重要的毒性机制。通过对相关基因分析，尼泊金酯类除了通过性激素受体介导生殖毒性外，还可能影响激素的合成与转运；尼泊金酯类对脂代谢的影响主要表现为对脂肪分化与脂肪因子分泌相关基因的影响。KEGG通路富集分析中，发现大量与生殖相关通路，主要包括两大类：一类与生殖相关激素的合成、分泌及活性有关；另一类则主要与卵巢发育有关。另外，还发现了大量与神经突触信号传递、突触导向、突触可塑性以及神经网络形成等相关的通路，主要与尼泊金丁酯和尼泊金丙酯有关。尽管在尼泊金酯的生殖毒性方面已经开展了大量研究，但尼泊金酯对神经-行为学影响的数据资料还较少，特别是动物实验数据，亟需在该方面开展大量研究，进而对尼泊金酯进行更加全面的生态和健康风险评估。
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关键词:
- 尼泊金酯 /
- 比较毒理基因组学数据库 /
- 综合毒性 /
- 毒性机制
Abstract: Parabens are widely used as preservatives in cosmetics, food or drugs, and thus their impact on ecology or human health has attracted great concern. Comparative Toxicogenomics Database (CTD) has been becoming an important resource for research of toxicological informatics. This study analyzed genes and pathways associated with five commonly used parabens by manual curation using CTD. It is found that the five parabens co-affected genes mainly included estrogen receptors or genes involved in lipid metabolism. The nuclear receptor mechanism, especially for estrogen receptors, might be an important toxicological mechanism for all parabens. By analyzing related genes, in addition to sex hormone receptors, synthesis and transport of sex hormones might be also involved in the reproductive toxicity caused by exposure to parabens. The effects of parabens on lipid metabolism are mainly related to genes for adipocyte differentiation or adipokines. A large number of reproduction related pathways are found, mainly including two categories. One is related to the synthesis, secretion and activity of reproduction related hormones, and the other is mainly related to ovarian development. A large number of pathways related to synaptic signaling, targeting and plasticity, or neural network formation have been found, mainly affected by butylparaben or propylparaben. Despite of the increasing research on reproductive toxicity of parabens, few data of neuro-behavioral effects of parabens, especially animal experimental data, are available. Thus, further research on neurotoxicology is urgently needed for more comprehensively ecological and health risk assessment.-
Key words:
- paraben /
- Comparative Toxicogenomics Database /
- integrated toxicity /
- toxicity mechanism
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