School of Health Sciences, Purdue University, West Lafayette, Indiana 47907, United States.
Purdue Institute for Integrative Neurosciences, Purdue University, West Lafayette, Indiana 47907, United States.
Chem Res Toxicol. 2022 Jan 17;35(1):59-72. doi: 10.1021/acs.chemrestox.1c00274. Epub 2022 Jan 6.
Heterocyclic aromatic amines (HAAs) are mainly formed in the pyrolysis process during high-temperature cooking of meat. Meat consumption is very typical of the western diet, and the amount of meat consumption in the eastern countries is growing rapidly; HAAs represents widespread exposure. HAAs are classified as possible human carcinogens; numerous epidemiological studies have demonstrated regular consumption of meat with HAAs as risk factor for cancers. Specific HAAs have received major attention. For example, 2-amino-1-methyl-6-phenylimidazo[4,5-] pyridine has been extensively studied as a genotoxicant and mutagen, with emergent literature on neurotoxicity. Harmane has been extensively studied for a role in essential tremors and potentially Parkinson's disease (PD). Harmane levels have been demonstrated to be elevated in blood and brain in essential tremor patients. Meat consumption has been implicated in the etiology of neurodegenerative diseases; however, the role of toxicants formed during meat preparation has not been studied. Epidemiological studies are currently examining the association between HAAs and risk of neurodegenerative diseases such as essential tremors and PD. Studies from our laboratory and others have provided strong evidence that HAA exposure produces PD and Alzheimer's disease-relevant neurotoxicity in cellular and animal models. In this review, we summarize and critically evaluate previous studies on HAA-induced neurotoxicity and the molecular basis of potential neurotoxic effects of HAAs. The available studies provide strong support for the premise that HAAs may impact neurological function and that addressing gaps in understanding of adverse neurological outcomes is critical to determine whether these compounds are modifiable risk factors.
杂环胺（HAAs）主要在高温烹饪肉类的热解过程中形成。肉类消费是西方饮食的典型特征，而东方国家的肉类消费量正在迅速增长；HAAs 代表了广泛的暴露。HAAs 被归类为可能的人类致癌物；大量的流行病学研究表明，经常食用含有 HAAs 的肉类是癌症的风险因素。特定的 HAAs 受到了广泛关注。例如，2-氨基-1-甲基-6-苯基咪唑[4,5-b]吡啶已被广泛研究为遗传毒性和致突变剂，新兴文献涉及神经毒性。哈尔曼因在特发性震颤和潜在的帕金森病（PD）中的作用而被广泛研究。已证明哈尔曼在特发性震颤患者的血液和大脑中的水平升高。肉类消费与神经退行性疾病的病因有关；然而，在肉类制备过程中形成的毒物的作用尚未得到研究。流行病学研究目前正在检查 HAAs 与特发性震颤和 PD 等神经退行性疾病风险之间的关联。我们实验室和其他实验室的研究提供了强有力的证据，表明 HAA 暴露会在细胞和动物模型中产生 PD 和阿尔茨海默病相关的神经毒性。在这篇综述中，我们总结和批判性地评估了先前关于 HAA 诱导的神经毒性以及 HAAs 潜在神经毒性作用的分子基础的研究。现有研究为以下前提提供了强有力的支持：HAAs 可能会影响神经功能，并且了解不良神经后果方面的差距对于确定这些化合物是否是可改变的风险因素至关重要。
