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从细胞到器官:探索有机磷化合物在生命系统中的毒理学关联。

From cell to organ: Exploring the toxicological correlation of organophosphorus compounds in living system.

作者信息

Yadav Pooja, Nair Ashrit, Chawla Raman, Ghosh Subhajit, Aleem Mohd, Butola Bhupendra Singh, Sharma Navneet, Khan Haider Ali

机构信息

Department of Medical Elementology and Toxicology, Jamia Hamdard, Delhi 110062, India.

Department of Textile and Fiber Engineering, Indian Institute of Technology Delhi, 110016, India.

出版信息

Toxicology. 2025 Feb;511:154049. doi: 10.1016/j.tox.2025.154049. Epub 2025 Jan 10.

Abstract

Malathion is an organophosphate compound widely used as an insecticide in the agriculture sector and is toxic to humans and other mammals. Although several studies have been conducted at different levels in different animal models. But there is no work has been conducted on the toxicological correlation from cellular to behavioral level in surviving species model. Addressing this gap through further research is essential for a comprehensive understanding of malathion's impact on biological systems, facilitating better risk assessment and management strategies. Current research systemically evaluated the effects of malathion on the central nervous system and peripheral immune cells using immunological techniques in the BALB/c mice models. For this, animals were placed inside an inhalation chamber containing malathion (dose of 89.5 mg/ml/m) for a specific exposure time. The group exposed for 6 minutes has shown a significant change in plasma-neurotransmitter (serotonin, dopamine) levels and decreased expression of Tyrosine hydroxylase in striatum and SNPC region of brain. The depolarized mitochondria and increased level of cleaved caspase-3 level and mature neurons in DG, CA1 and CA3 were also observed in the brain. Peripheral blood analysis illustrated a decrease in total leukocyte count and an increased level of early apoptosis at the same time point. From neurobehavioral results a significant locomotor hyperactivity, restlessness, and risk-taking behavior was observed. Taken together, results from the current study indicate that exposure to malathion at prolonged time durations induces neuronal and immune cell toxicity, and its toxicity may be mediated via changes in neurotransmitter levels and metabolite concentrations.

摘要

马拉硫磷是一种有机磷化合物,在农业领域广泛用作杀虫剂,对人类和其他哺乳动物有毒。尽管已经在不同的动物模型中进行了多个层面的研究,但尚未在存活物种模型中开展从细胞水平到行为水平的毒理学相关性研究。通过进一步研究填补这一空白对于全面了解马拉硫磷对生物系统的影响、促进更好的风险评估和管理策略至关重要。当前的研究在BALB/c小鼠模型中使用免疫学技术系统地评估了马拉硫磷对中枢神经系统和外周免疫细胞的影响。为此,将动物置于含有马拉硫磷(剂量为89.5毫克/毫升/米)的吸入室内特定暴露时间。暴露6分钟的组血浆神经递质(血清素、多巴胺)水平出现显著变化,脑纹状体和黑质致密部区域酪氨酸羟化酶表达降低。在脑中还观察到线粒体去极化、裂解的半胱天冬酶-3水平升高以及齿状回、海马体CA1和CA3区成熟神经元数量增加。外周血分析表明在同一时间点总白细胞计数减少且早期凋亡水平升高。从神经行为学结果来看,观察到明显的运动活动亢进、烦躁不安和冒险行为。综上所述,当前研究结果表明长时间暴露于马拉硫磷会诱导神经元和免疫细胞毒性,其毒性可能通过神经递质水平和代谢物浓度的变化介导。

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