Institute of Metabolic Diseases, Qingdao University, Qingdao, China; Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, China; Shandong Provincial Clinical Research Center for Immune Diseases and Gout, the Affiliated Hospital of Qingdao University, Qingdao, China.
Plateau Atmosphere and Environment Key Laboratory of Sichuan Province, School of Atmospheric Sciences, Chengdu University of Information Technology, China.
Ecotoxicol Environ Saf. 2023 Nov 1;266:115587. doi: 10.1016/j.ecoenv.2023.115587. Epub 2023 Oct 13.
Cadmium (Cd) exposure has been associated with the development of enterohepatic circulation disorders and hyperuricemia, but the possible contribution of chronic low-dose Cd exposure to disease progression is still need to be explored. A mouse model of wild-type mice (WT) and Uox-knockout mice (Uox-KO) to find out the toxic effects of chronic low-dose Cd exposure on liver purine metabolism by liquid chromatography-mass spectrometry (LC-MS) platform and associated intestinal flora. High throughput omics analysis including metabolomics and transcriptomics showed that Cd exposure can cause disruption of purine metabolism and energy metabolism. Cd changes several metabolites associated with purine metabolism (xanthine, hypoxanthine, adenosine, uridine, inosine) and related genes, which are associated with elevated urate levels. Microbiome analysis showed that Cd exposure altered the disturbance of homeostasis in the gut. Uox-KO mice were more susceptible to Cd than WT mice. Our findings extend the understanding of potential toxicological interactions between liver and gut microbiota and shed light on the progression of metabolic diseases caused by Cd exposure.
镉（Cd）暴露与肠肝循环紊乱和高尿酸血症的发展有关，但慢性低剂量 Cd 暴露对疾病进展的可能贡献仍需要进一步研究。本研究构建了野生型（WT）和尿卟啉原氧化酶敲除（Uox-KO）小鼠模型，通过液相色谱-质谱（LC-MS）平台和相关肠道菌群，研究慢性低剂量 Cd 暴露对肝脏嘌呤代谢的毒性作用。高通量组学分析包括代谢组学和转录组学，结果表明 Cd 暴露可导致嘌呤代谢和能量代谢紊乱。Cd 改变了几种与嘌呤代谢相关的代谢物（黄嘌呤、次黄嘌呤、腺苷、尿苷、肌苷）及其相关基因，这些代谢物与尿酸水平升高有关。微生物组分析表明，Cd 暴露改变了肠道内稳态的紊乱。与 WT 小鼠相比，Uox-KO 小鼠对 Cd 更敏感。我们的研究结果扩展了对肝脏和肠道微生物群之间潜在毒理学相互作用的理解，并为 Cd 暴露引起的代谢性疾病的进展提供了新的见解。
