Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA; Pediatric Research Institute, The Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA; Pediatric Research Institute, The Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Environ Int. 2022 Jan;158:106877. doi: 10.1016/j.envint.2021.106877. Epub 2021 Sep 20.
Hexavalent chromium [Cr(VI)] is a global environmental pollutant that increases risk for several types of cancers and is increasingly being recognized as a neurotoxicant. Traditionally, the brain has been viewed as a largely post-mitotic organ due to its specialized composition of neurons, and consequently, clastogenic effects were not considered in neurotoxicology. Today, we understand the brain is composed of at least eight distinct cell types - most of which continue mitotic activity throughout lifespan. We have learned these dividing cells play essential roles in brain and body health. This review focuses on Cr(VI), a potent clastogen and known human carcinogen, as a potentially neurotoxic agent targeting mitotic cells of the brain. Despite its well-established role as a human carcinogen, Cr(VI) neurotoxicity studies have failed to find a significant link to brain cancers. In the few studies that did find a link, Cr(VI) was identified as a risk for gliomas. Instead, in the human brain, Cr(VI) appears to have more subtle deleterious effects that can impair childhood learning and attention development, olfactory function, social memory, and may contribute to motor neuron diseases. Studies of Cr(VI) neurotoxicity with animal and cell culture models have demonstrated elevated markers of oxidative damage and redox stress, with widespread neurodegeneration. One study showed mice exposed to Cr(VI)-laden tannery effluent exhibited longer periods of aggressive behavior toward an "intruder" mouse and took longer to recognize mice previously encountered, recapitulating the social memory deficits observed in humans. Here we conducted a critical review of the available literature on Cr(VI) neurotoxicity and synthesize the collective observations to thoroughly evaluate Cr(VI) neurotoxicity - much remains to be understood and recognized.
六价铬[Cr(VI)]是一种全球性的环境污染物，会增加多种癌症的风险，并且越来越被认为是一种神经毒物。传统上，由于大脑神经元的特殊组成，大脑被认为是一个主要的有丝分裂后器官，因此，在神经毒理学中没有考虑到致裂效应。如今，我们知道大脑由至少八种不同的细胞类型组成-其中大多数在整个生命周期中都继续有丝分裂活动。我们已经了解到这些分裂细胞在大脑和身体健康中起着至关重要的作用。这篇综述重点介绍 Cr(VI)，一种有效的致裂剂和已知的人类致癌物，作为一种潜在的神经毒性剂，针对大脑的有丝分裂细胞。尽管 Cr(VI)已被确立为人类致癌物，但 Cr(VI)的神经毒性研究未能发现与脑癌之间的显著联系。在少数发现联系的研究中，Cr(VI)被确定为神经胶质瘤的危险因素。相反，在人类大脑中，Cr(VI)似乎具有更微妙的有害影响，会损害儿童的学习和注意力发展、嗅觉功能、社会记忆，并可能导致运动神经元疾病。动物和细胞培养模型的 Cr(VI)神经毒性研究表明，氧化损伤和氧化应激的标志物升高，广泛的神经退行性变。一项研究表明，暴露于含 Cr(VI)的制革厂废水中的小鼠对“入侵者”老鼠表现出更长时间的攻击性行为，并且需要更长的时间才能识别以前遇到过的老鼠，这再现了在人类中观察到的社会记忆缺陷。在这里，我们对现有的 Cr(VI)神经毒性文献进行了批判性回顾，并综合了这些观察结果，以彻底评估 Cr(VI)神经毒性-仍有许多问题需要了解和认识。
