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长期暴露于 2-氨基-3-甲基咪唑[4,5-f]喹啉可能会引发帕金森病的潜在风险。

Long-term exposure to 2-amino-3-methylimidazo[4,5-f]quinoline can trigger a potential risk of Parkinson's disease.

机构信息

Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China.

Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China.

出版信息

J Hazard Mater. 2021 Jun 15;412:125230. doi: 10.1016/j.jhazmat.2021.125230. Epub 2021 Jan 27.

Abstract

Humans are exposed to heterocyclic amines (HCAs) from a wide range of sources, such as protein-rich thermally processed foods, cigarette smoke, contaminated river water, the atmosphere, soil, and forest fire ash. Although the carcinogenic and mutagenic hazards of HCAs have been widely studied, the potential neurotoxicity of these compounds still needs to be further elucidated. Here, we studied the neurotoxicity of the HCA 2-amino-3-methylimidazole[4,5-f]quinoline (IQ) in vivo by utilizing a zebrafish model. After 35 days of exposure at 8, 80, and 800 ng/mL, zebrafish exploratory behavior and locomotor activity were significantly inhibited, and light/dark preference behaviors were also disturbed. Moreover, the expression of Parkinson's disease (PD)-related genes and proteins, dopamine-related genes, neuroplasticity-related genes, antioxidant enzyme genes and inflammatory cytokine genes in the zebrafish brain was significantly affected. The numbers of NeuN neurons in the midbrain were decreased in exposed zebrafish, while the numbers of apoptotic cells were increased. In summary, our research suggests that IQ is neurotoxic and significantly associated with PD and that long-term exposure to IQ may contribute to PD risk. This risk may be related to IQ-mediated effects on mitochondrial homeostasis and induction of oxidative stress and inflammation.

摘要

人类会从多种来源接触到杂环胺(HCAs),例如富含蛋白质的经热处理的食物、香烟烟雾、受污染的河水、大气、土壤和森林火灾灰。虽然杂环胺的致癌和致突变危害已得到广泛研究,但这些化合物的潜在神经毒性仍需要进一步阐明。在这里,我们利用斑马鱼模型研究了杂环胺 2-氨基-3-甲基咪唑[4,5-f]喹啉(IQ)的体内神经毒性。在 8、80 和 800ng/mL 下暴露 35 天后,斑马鱼的探索行为和运动活性明显受到抑制,光/暗偏好行为也受到干扰。此外,斑马鱼大脑中帕金森病(PD)相关基因和蛋白、多巴胺相关基因、神经可塑性相关基因、抗氧化酶基因和炎症细胞因子基因的表达也受到显著影响。暴露于 IQ 中的斑马鱼中中脑的 NeuN 神经元数量减少,而凋亡细胞数量增加。总之,我们的研究表明,IQ 具有神经毒性,与 PD 显著相关,长期暴露于 IQ 可能会增加 PD 风险。这种风险可能与 IQ 介导的线粒体动态平衡的破坏以及氧化应激和炎症的诱导有关。

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