Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
Center for Preventive Medical Sciences, Chiba University, Inage-ku Yayoi-cho 1-33, Chiba 263-8522, Japan.
Int J Environ Res Public Health. 2022 Jan 4;19(1):541. doi: 10.3390/ijerph19010541.
Lead poisoning is often considered a traditional disease; however, the specific mechanism of toxicity remains unclear. The study of Pb-induced alterations in cellular metabolic pathways is important to understand the biological response and disorders associated with environmental exposure to lead. Metabolomics studies have recently been paid considerable attention to understand in detail the biological response to lead exposure and the associated toxicity mechanisms. In the present study, wild rodents collected from an area contaminated with lead (N = 18) and a control area (N = 10) were investigated. This was the first ever experimental metabolomic study of wildlife exposed to lead in the field. While the levels of plasma phenylalanine and isoleucine were significantly higher in a lead-contaminated area versus the control area, hydroxybutyric acid was marginally significantly higher in the contaminated area, suggesting the possibility of enhancement of lipid metabolism. In the interregional least-absolute shrinkage and selection operator (lasso) regression model analysis, phenylalanine and isoleucine were identified as possible biomarkers, which is in agreement with the random forest model. In addition, in the random forest model, glutaric acid, glutamine, and hydroxybutyric acid were selected. In agreement with previous studies, enrichment analysis showed alterations in the urea cycle and ATP-binding cassette transporter pathways. Although regional rodent species bias was observed in this study, and the relatively small sample size should be taken into account, the present results are to some extent consistent with those of previous studies on humans and laboratory animals.
铅中毒通常被认为是一种传统疾病；然而，其毒性的具体机制仍不清楚。研究 Pb 诱导的细胞代谢途径改变对于理解与环境铅暴露相关的生物学反应和紊乱非常重要。代谢组学研究最近受到了相当多的关注，以详细了解对铅暴露的生物学反应和相关毒性机制。在本研究中，从受铅污染地区（N = 18）和对照地区（N = 10）采集了野生啮齿动物进行研究。这是首次在野外对受铅污染的野生动物进行的实验代谢组学研究。虽然受污染地区血浆苯丙氨酸和异亮氨酸的水平明显高于对照地区，但羟丁酸的水平略有显著升高，这表明脂代谢可能增强。在区域间最小绝对收缩和选择算子（lasso）回归模型分析中，苯丙氨酸和异亮氨酸被鉴定为可能的生物标志物，这与随机森林模型一致。此外，在随机森林模型中，还选择了谷氨酸、谷氨酰胺和羟丁酸。与之前的研究一致，富集分析显示尿素循环和 ABC 转运蛋白途径发生改变。尽管本研究观察到了区域啮齿动物物种的偏见，且样本量相对较小，但目前的结果在一定程度上与之前对人类和实验室动物的研究结果一致。
