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利用空间代谢组学分析发现碳量子点在小鼠大脑中引起的区域神经毒性相关代谢改变。

The discovery of regional neurotoxicity-associated metabolic alterations induced by carbon quantum dots in brain of mice using a spatial metabolomics analysis.

机构信息

Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, 210009, Nanjing, P.R. China.

出版信息

Part Fibre Toxicol. 2024 Apr 10;21(1):19. doi: 10.1186/s12989-024-00580-y.

DOI:10.1186/s12989-024-00580-y
PMID:38600504
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11005155/
Abstract

BACKGROUND

Recently, carbon quantum dots (CQDs) have been widely used in various fields, especially in the diagnosis and therapy of neurological disorders, due to their excellent prospects. However, the associated inevitable exposure of CQDs to the environment and the public could have serious severe consequences limiting their safe application and sustainable development.

RESULTS

In this study, we found that intranasal treatment of 5 mg/kg BW (20 µL/nose of 0.5 mg/mL) CQDs affected the distribution of multiple metabolites and associated pathways in the brain of mice through the airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) technique, which proved effective in discovery has proven to be significantly alerted and research into tissue-specific toxic biomarkers and molecular toxicity analysis. The neurotoxic biomarkers of CQDs identified by MSI analysis mainly contained aminos, lipids and lipid-like molecules which are involved in arginine and proline metabolism, biosynthesis of unsaturated fatty acids, and glutamine and glutamate metabolism, etc. as well as related metabolic enzymes. The levels or expressions of these metabolites and enzymes changed by CQDs in different brain regions would induce neuroinflammation, organelle damage, oxidative stress and multiple programmed cell deaths (PCDs), leading to neurodegeneration, such as Parkinson's disease-like symptoms. This study enlightened risk assessments and interventions of QD-type or carbon-based nanoparticles on the nervous system based on toxic biomarkers regarding region-specific profiling of altered metabolic signatures.

CONCLUSION

These findings provide information to advance knowledge of neurotoxic effects of CQDs and guide their further safety evaluation.

摘要

背景

由于具有广阔的应用前景,近年来碳量子点(CQDs)已被广泛应用于各个领域,特别是在神经疾病的诊断和治疗方面。然而,CQDs 在环境和公众中不可避免的存在会产生严重的后果,限制了其安全应用和可持续发展。

结果

在本研究中,我们发现经鼻给予 5mg/kg BW(20 µL/鼻腔,浓度为 0.5mg/mL)的 CQDs 通过气流辅助解吸电喷雾电离质谱成像(AFADESI-MSI)技术影响了小鼠大脑中多种代谢物的分布和相关代谢途径,该技术已被证明在发现组织特异性毒性生物标志物和分子毒性分析方面具有显著的预警作用。MSI 分析鉴定的 CQD 神经毒性生物标志物主要包含氨基酸、脂质和类脂分子,涉及精氨酸和脯氨酸代谢、不饱和脂肪酸的生物合成以及谷氨酰胺和谷氨酸代谢等,以及相关的代谢酶。CQDs 改变了不同脑区这些代谢物和酶的水平或表达,会引发神经炎症、细胞器损伤、氧化应激和多种程序性细胞死亡(PCD),导致神经退行性变,如帕金森病样症状。本研究为基于代谢特征的特定区域分析,针对基于神经毒性生物标志物的 QD 型或碳基纳米粒子对神经系统的风险评估和干预提供了信息。

结论

这些发现为深入了解 CQDs 的神经毒性作用提供了信息,并为进一步的安全评估提供了指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/d35c93428b0d/12989_2024_580_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/70e997b64e44/12989_2024_580_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/0b10d2eca3b1/12989_2024_580_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/05652da0c990/12989_2024_580_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/419016b21178/12989_2024_580_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/ea08a7521758/12989_2024_580_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/f87e8ae506a6/12989_2024_580_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/6e00d2593c89/12989_2024_580_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/eac68cd9f001/12989_2024_580_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/d35c93428b0d/12989_2024_580_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/70e997b64e44/12989_2024_580_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/0b10d2eca3b1/12989_2024_580_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/05652da0c990/12989_2024_580_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/419016b21178/12989_2024_580_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/ea08a7521758/12989_2024_580_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/f87e8ae506a6/12989_2024_580_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/6e00d2593c89/12989_2024_580_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/eac68cd9f001/12989_2024_580_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ed/11005155/d35c93428b0d/12989_2024_580_Fig9_HTML.jpg

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