Integrated transcriptome-metabolome analysis reveals attenuated combined toxicity: Antagonistic interactions of three thermal processing contaminants in murine kidney-urine systems
To investigate the toxicological effects after individual or combined sub-chronical exposure to oxidized triacylglycerols, aldehydes, and 3-MCPDE formed during thermal processing of high-fat foods, this study implemented transcriptome-metabolome analysis of renal tissues in Kunming mice, supplemented with urine metabolomics study. Transcriptomic analysis highlighted perturbations in the PI3K-Akt signaling pathway, while metabolomic and integrated analyses both identified disruptions in glycerophospholipid metabolism. Urine metabolomic results further corroborated renal dysfunction, with altered tryptophan and purine metabolism. Results revealed that the exposure of three toxicants induced multi-organ metabolic network encompassing the kidney, liver, and even nervous system. Toxic effects were less pronounced when the three toxicants were exposed in combination while compared to their individual effects, suggesting the necessity for further investigation in the potential antagonistic mechanisms. Results provide critical insights into the co-exposure toxicity and interaction mechanisms of thermally induced toxicants in high-fat foods, offering toxicological foundations for establishing safety regulations.