Cadmium exposure dysregulates purine metabolism and homeostasis across the gut-liver axis in a mouse model.

Abstract

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.

• Authors: Hui Zhang, Meng Xiu, Hailong Li, Maichao Li, Xiaomei Xue, Yuwei He, Wenyan Sun, Xuan Yuan, Zhen Liu, Xinde Li, Tony R Merriman, Changgui Li
• Journal: Ecotoxicology and environmental safety (Ecotoxicol Environ Saf) Vol. 266 Pg. 115587 (Nov 01 2023) ISSN: 1090-2414 [Electronic] Netherlands
• PMID: 37837700 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cadmium

Topics

• Animals
• Mice
• Cadmium (metabolism)
• Liver
• Metabolomics
• Homeostasis
• Gastrointestinal Microbiome
• Disease Models, Animal