Abstract
Copper, an essential trace element, is indispensable for the growth and physiological functions of living beings, influencing several critical processes like cellular energy production, antioxidant defense, communication within cells, and functioning of enzymes. However, when copper levels exceed normal limits, it can lead to significant health issues. Recent investigations into the adverse effects of copper have shed light on its toxicological impacts, particularly focusing on metabolic alterations in certain organs. Yet, comprehensive research that examines the primary organs at risk from copper toxicity through a metabolomic lens remains scarce. In this study, an untargeted metabolomics strategy was adopted to assess how copper exposure alters organ metabolites leveraging gas chromatography-mass spectrometry (GC-MS) with the aim of identifying possible biomarkers and investigating their association with metabolic pathway disorders. Male C57BL/6J mice were randomly assigned to different experimental groups and metabolite levels in different organs were measured using GC-MS. Analyses showed very different metabolite profiles between groups, with 11, 32, 12, 18, 16, 15, 9, and 27 metabolites identified and 14 metabolites altered in serum, liver, kidney, muscle, hippocampus, cortex, lung, and pancreas, respectively, and examined the relationship between metabolites and metabolic pathways. Our findings reveal that copper is closely associated with disruption of metabolic pathways, and that copper can trigger a wide range of toxic effects through multiple pathways, such as triggering oxidative stress, interfering with mitochondrial function, altering enzyme function, weakening the body's ability to detoxify, and interfering with cell signaling. These findings reveal the complex mechanisms of copper toxicity and provide valuable information for the development of preventive and therapeutic measures for copper toxicity.