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LC/MS/MS-Based Liver Metabolomics to Identify Chronic Liver Injury Biomarkers Following Exposure to Arsenic in Rats

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Abstract

Arsenic is a widespread natural metalloid element. Long-term chronic exposure to arsenic can lead to different degrees of liver injury. Although the etiology of this disease is well known, to date, the underlying mechanism of arsenic-induced liver injury remains unclear, and no specific treatment exists because of the complexity of arsenic. In the present study, potential biomarkers and metabolic pathways in the livers of Wistar rats treated with arsenic for 24 weeks were investigated using an integrated metabolic approach with an LC-Orbitrap Q Exactive™ HF-X mass spectrometer. Markedly increased liver levels of arsenic, alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bile acid (TBA) were detected in the arsenic treatment groups (P < 0.05). Furthermore, histopathological examination of liver tissues showed obviously swollen, loose cytoplasm and increased necrosis in the arsenic treatment groups compared with those in the control group (P < 0.05). Metabonomics results showed that 109 metabolites (variable importance in the projection (VIP) > 1; fold change > 2 or < 0.5; P adjusted < 0.05) changed significantly after exposure to arsenic and included 71 upregulated metabolites and 38 downregulated metabolites. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that 6 metabolic pathways with statistical significance—phenylalanine metabolism, pyruvate metabolism, glycolysis/gluconeogenesis, citrate cycle (TCA cycle), thiamine metabolism, and vitamin B6 metabolism—were selected, and 13 differential metabolites were detected to be involved in regulating these metabolic pathways. The present study could help identify potential biomarkers and their functions, as well as metabolic pathways, likely providing evidence for the early diagnosis, prevention, and mechanistic study of arsenism.

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Data Availability

The datasets generated during and/or processed during the current study cannot be shared at this time as the data forms part of an ongoing study but are available from the corresponding author on reasonable request.

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Funding

This work was funded by grants from the National Natural Science Foundation of China (grant no. 81860561, 81430077, U1812403, and 82160649).

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Authors and Affiliations

  1. Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 550025, Guizhou, China

    Dingnian Bi, Mingyang Shi, Qian Hu, Hongling Wang, Aihua Zhang & Yong Hu

  2. Department of Forensic Medicine, Guizhou University of Traditional Chinese Medicine, Guizhou, 550025, China

    Didong Lou

  3. Key Laboratory of Traditional Chinese Medicine Toxicology in Forensic Medicine, Guizhou Education Department, Guizhou, 550025, China

    Didong Lou

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  1. Dingnian Bi
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  2. Mingyang Shi
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  3. Qian Hu
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  4. Hongling Wang
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  5. Didong Lou
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  6. Aihua Zhang
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  7. Yong Hu
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Contributions

Hu Y and Zhang A contributed to the study’s conception and supervision. Bi D, Shi M, Hu Q, and Wang H performed the research. Lou D gave the assistance in consulting and collecting relevant data. All authors contributed to data analysis and interpretation and approved the final manuscript for submission.

Corresponding author

Correspondence to Yong Hu.

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The authors declare no competing interests.

Research Involving Human Participants and/or Animals

All procedures performed in studies involving animals were in accordance with the Guide for the Care and Use of Laboratory Animals (National Research Council, 1996). And the study was approved by the Animal Care Welfare Committee of Guizhou Medical University.

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Bi, D., Shi, M., Hu, Q. et al. LC/MS/MS-Based Liver Metabolomics to Identify Chronic Liver Injury Biomarkers Following Exposure to Arsenic in Rats. Biol Trace Elem Res 200, 4355–4369 (2022). https://doi.org/10.1007/s12011-021-03026-0

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  • DOI: https://doi.org/10.1007/s12011-021-03026-0

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