Toxicity assessment due to prenatal and lactational exposure to lead, cadmium and mercury mixtures
Toxicity assessment due to prenatal and lactational exposure to lead, cadmium and mercury mixtures
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产前和哺乳期接触铅、镉和汞混合物的毒性评估
DOI：
10.1016/j.envint.2019.105192
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发表时间：
2019
影响因子：
11.8
通讯作者：
Fan Guangqin
中科院分区：
文献类型：
--
作者：
Zhou Fankun;Yin Guangming;Gao Yanyan;Liu Dong;Xie Jie;Ouyang Lu;Fan Ying;Yu Han;Zha Zhipeng;Wang Kai;Shao Lijian;Feng Chang;Fan Guangqin
重金属铅（Pb）、镉（Cd）和汞（Hg）是常见的环境污染物，可以在一般人群的血液、血清和尿液样本中同时检测到。然而，关于低水平接触铅、镉和汞混合物的毒性的信息有限。我们之前的研究显示了这三种元素在体外低浓度下的相互作用。在这项研究中，我们进一步评估了低剂量暴露于铅、镉和汞混合物对大鼠大脑、心脏、肝脏、肾脏和睾丸的早期影响。怀孕的大鼠在妊娠和哺乳期间暴露于饮用水中不同浓度的重金属混合物 (MM)，并在出生后第 23 天测量对后代的影响。我们的结果表明，幼鼠血液中的 Pb、Cd 和 Hg 浓度与一般人类血液中的浓度相似。此外，他们血液和大脑中的 MM 浓度以剂量依赖性方式显着增加。 MM 暴露引起大脑、肝脏、肾脏和睾丸的组织病理学变化。观察到肝脏 CYP450 和 PON1、肾脏 KIM1 显着增加以及睾丸 SDH 减少。在大脑中，氧化应激、细胞内游离钙和细胞凋亡显着增加。进一步的神经行为测试表明，MM 暴露会导致学习、记忆以及感觉知觉的剂量依赖性损害。 MM 暴露还会破坏突触重塑，这可能与树突棘生长、维持和消除有关的途径有关。这些结果表明，在人类环境暴露相关水平下，暴露于铅、镉和汞混合物会导致大鼠的多个器官受损以及神经行为功能受损。我们的研究结果强调需要控制和监管潜在的重金属污染源。
The heavy metals lead (Pb), cadmium (Cd) and mercury (Hg) are common environmental pollutants that can be detected simultaneously in blood, serum, and urine samples from the general human population. However, there is limited information regarding toxicity of low-level exposure to Pb, Cd, and Hg mixtures. Our previous research showed the interaction of these three elements at low concentrationsin vitro. In this study, we further evaluate early effects of low dose exposure to Pb, Cd, and Hg mixtures on the brain, heart, liver, kidney, and testicle in rats. Pregnant rats were exposed to various concentrations of heavy metal mixtures (MM) in drinking water, during gestation and lactation, and the impacts on offspring were measured at postnatal day 23. Our results showed that the concentrations of Pb, Cd, and Hg in the blood of rat pups were similar to those in the blood of the general human population. Additionally, the MM concentrations in their blood and brain significantly increased in a dose-dependent manner. MM exposure caused histopathological changes in the brain, liver, kidney and testicle. Statistically significant increases in liver CYP450 and PON1, kidney KIM1, and decrease in testicle SDH were observed. In the brain, significant increases were detected in oxidative stress, intracellular free calcium, and cell apoptosis. Further neurobehavioral testing revealed that MM exposure caused dose-dependent impairments in learning and memory as well as sensory perception. MM exposure also disrupted synapse remodeling, which may be associated with pathways involved in dendritic spine growth, maintenance, and elimination. These results suggested that exposure to Pb, Cd, and Hg mixtures, at human environmental exposure related levels, caused damage to multiple organs as well as impairments in neurobehavioral functions of rats. Our findings emphasize the need to control and regulate potential sources of heavy metal contamination.