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钴、镍和铅的单一及二元混合物对海马神经元细胞的神经毒性机制评估

Assessment of Neurotoxic Mechanisms of Individual and Binary Mixtures of Cobalt, Nickel and Lead in Hippocampal Neuronal Cells.

作者信息

Olasehinde Tosin A, Olaniran Ademola O

机构信息

Nutrition and Toxicology Division, Food Technology Department, Federal Institute of Industrial Research, Lagos, Nigeria.

Discipline of Microbiology, School of Life Sciences, University of Kwazulu-Natal, Durban, South Africa.

出版信息

Environ Toxicol. 2025 Jan;40(1):128-139. doi: 10.1002/tox.24418. Epub 2024 Oct 4.

DOI:10.1002/tox.24418
PMID:39365032
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11628647/
Abstract

Many studies have focused on the neurotoxic effects of single metals, while investigation on the exposure to metal mixtures, which mainly occur in real-life situations, is scarce. This study sought to assess the neurotoxic effect of Ni, Co, and Pb binary mixtures and their individual effects in hippocampal neuronal cells (HT-22). Cells were exposed to Ni, Co, and Pb separately for 48 h at 37°C and 5% CO, and cell viability was assessed. Morphological assessment of the cells exposed to binary mixtures of Co, Ni, and Pb and single metals was assessed using a microscope. Furthermore, acetylcholinesterase (AChE) activity, oxidative stress biomarkers (glutathione [GSH] and malondialdehyde [MDA] levels, catalase [CAT], and glutathione-S transferase [GST] activities) and nitric oxide [NO] levels were evaluated after treatment with the binary mixtures and single metals. Binary mixtures of the metals reduced cell viability, exerting an additivity action. The combinations also exerted synergistic action, as revealed by the combination index. Furthermore, a significant reduction in AChE activity, GSH levels, CAT and GST activities, and high MDA and NO levels were observed in neuronal cells. The additive interactions and synergistic actions of the binary mixtures might contribute to the significant reduction of AChE activity, GSH levels, GST, and CAT activities, and an increase in MDA and NO levels. The findings from this study revealed significant evidence that binary mixtures of Co, Pb, and Ni may induce impaired neuronal function and, ultimately, neurodegeneration.

摘要

许多研究都聚焦于单一金属的神经毒性作用,而对于主要发生在现实生活中的金属混合物暴露情况的研究却很少。本研究旨在评估镍、钴和铅二元混合物的神经毒性作用及其在海马神经元细胞(HT-22)中的个体效应。将细胞分别在37°C和5%二氧化碳条件下暴露于镍、钴和铅48小时,然后评估细胞活力。使用显微镜对暴露于钴、镍和铅二元混合物及单一金属的细胞进行形态学评估。此外,在用二元混合物和单一金属处理后,评估乙酰胆碱酯酶(AChE)活性、氧化应激生物标志物(谷胱甘肽[GSH]和丙二醛[MDA]水平、过氧化氢酶[CAT]和谷胱甘肽-S转移酶[GST]活性)以及一氧化氮[NO]水平。金属二元混合物降低了细胞活力,表现出相加作用。组合指数显示这些组合还表现出协同作用。此外,在神经元细胞中观察到AChE活性、GSH水平、CAT和GST活性显著降低,以及MDA和NO水平升高。二元混合物的相加相互作用和协同作用可能导致AChE活性、GSH水平、GST和CAT活性显著降低,以及MDA和NO水平升高。本研究结果提供了重要证据,表明钴、铅和镍的二元混合物可能会导致神经元功能受损,并最终导致神经退行性变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a285/11628647/fac6720bd0df/TOX-40-128-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a285/11628647/f72dfa0d9201/TOX-40-128-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a285/11628647/90e73bdc3aeb/TOX-40-128-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a285/11628647/894b19e8b8aa/TOX-40-128-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a285/11628647/a341ea203c76/TOX-40-128-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a285/11628647/e393b1b16759/TOX-40-128-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a285/11628647/6836d5c38ba5/TOX-40-128-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a285/11628647/fac6720bd0df/TOX-40-128-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a285/11628647/f72dfa0d9201/TOX-40-128-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a285/11628647/90e73bdc3aeb/TOX-40-128-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a285/11628647/894b19e8b8aa/TOX-40-128-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a285/11628647/a341ea203c76/TOX-40-128-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a285/11628647/e393b1b16759/TOX-40-128-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a285/11628647/6836d5c38ba5/TOX-40-128-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a285/11628647/fac6720bd0df/TOX-40-128-g006.jpg

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