Toxicologic, transcriptomic, and metabolomic insights into the effect of a mixture of 26 veterinary antimicrobials on rat liver

• Published in: Chemosphere (Oxford) Vol. 315; p. 137752
• Main Authors: Luan, Yehui, Zhao, Junjie, Chen, Yanan, Shen, Jianzhong, Cheng, Linli
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2023
• Subjects: ADI; Animals; Humans; Joint toxicity; Liver - metabolism; Male; Mass Spectrometry; Metabolomics; Mixture contamination; Multi-omics study; Rats; Rats, Sprague-Dawley; Transcriptome; Veterinary antimicrobials; Veterinary antimicrobials; Multi-omics study; Mixture contamination; ADI; Joint toxicity
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2023.137752

To evaluate the maximum possible hazard of veterinary antimicrobial mixtures at doses accessible to humans, Sprague-Dawley male rats were orally dosed with a mixture of 26 commonly used veterinary antimicrobials for 90 consecutive days. The daily dosage of each component was 100 times (G1), 10 times (G2) and, 1 time (G3) of acceptable daily intake (ADI) in China. Hematology analysis and biochemical analysis found significant changes of several parameters, suggesting liver damage. Histopathological examination further indicated that mixtures of veterinary drugs at three levels caused obvious hepatotoxicity, and the severity of damage increased with dosage. LC-MS-based metabolomics analysis was carried out to detect metabolite changes in liver tissue. In G1, G2, and G3, 208, 165, and 195 differential accumulated metabolites (DAMs) compared with the Ctrl group were filtered, respectively. Similarly, RNA-seq helped us to filter a total of 183, 118, and 38 differentially expressed genes (DEGs) in G1, G2, and G3 compared with the Ctrl group, respectively. By integrating with the transcriptomic and metabolomic data, we revealed that mineral absorption, ascorbate and aldarate metabolism may be the major pathways affected by the veterinary antimicrobial mixtures in our study. This study provided useful data for the risk assessment of multiple chemicals. [Display omitted] •A mixture of 26 commonly used veterinary antimicrobials induced hepatotoxicity on rats at the dose of ADI level.•Possible major pathways affected by the veterinary antimicrobial mixtures were filtered.•Ugt1a1, Ugt2b15, and, Ugt2b35 were downregulated at three doses.