Leveraging metabolomics and ionomics to illuminate aluminum-induced toxicity in mouse organs

Aluminum, a widely prevalent environmental pollutant, has been established to exert toxic effects on multiple organs in the human body. To gain a comprehensive understanding of these toxic effects and the mechanisms involved, this study aimed to assess potential correlations between metabolites and ion data through metabolomic and ionomic analyses. We sought to explore the intricate impact of aluminum on various organs in mice. Gas chromatography-mass spectrometry (GC-MS) and inductively coupled plasma-mass spectrometry (ICP-MS) were employed to conduct metabolomic and ionomic analyses on the hippocampus, cortex, heart, liver, spleen, lung, kidney, bone, intestine, stomach, and serum of both control and aluminum-exposed mice. Besides, histological examinations and behavioral experiments were conducted. Multivariate analysis revealed 91 differential metabolites across various organs, primarily encompassing amino acids, fatty acids, and carbohydrates. The implicated abnormal metabolic pathways included amino acid metabolism, arachidonic acid metabolism, and glutathione metabolism. Additionally, alterations in the homeostasis of ions such as manganese, zinc, selenium, iron, copper, phosphorus, magnesium, and calcium were observed in various organs, potentially influencing the activity of critical enzymes. The changes in these potential biomarkers and ions suggest toxic mechanisms of aluminum exposure involving oxidative stress, inflammatory responses, cellular signal dysregulation, disruption of key enzyme activities, and impaired energy metabolism. This study provides a novel perspective on understanding the toxic mechanisms of aluminum exposure, potentially contributing to the prevention and treatment of aluminum toxicity. • Metabolomics and ionomics analysis investigated aluminum's effects on organs. • Key metabolic disruptions in amino acid, fatty acids, and carbohydrates metabolism. • Ionomic analysis showed altered manganese, zinc, selenium, iron, and other ions. • Aluminum toxicity linked to oxidative stress, inflammation, and enzyme dysregulation.