Multi-Omics Analyses Reveal the Mechanisms of Early Stage Kidney Toxicity by Diquat

Author:

Zhang Huazhong12,Zhang Jinsong12,Li Jinquan12,Mao Zhengsheng2,Qian Jian3,Zong Cheng4,Sun Hao12,Yuan Beilei4ORCID

Affiliation:

1. Department of Emergency, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

2. Institute of Poisoning, Nanjing Medical University, Nanjing 211100, China

3. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

4. College of Safety Science and Engineering, Nanjing Tech University, Nanjing 211816, China

Abstract

Diquat (DQ), a widely used bipyridyl herbicide, is associated with significantly higher rates of kidney injuries compared to other pesticides. However, the underlying molecular mechanisms are largely unknown. In this study, we identified the molecular changes in the early stage of DQ-induced kidney damage in a mouse model through transcriptomic, proteomic and metabolomic analyses. We identified 869 genes, 351 proteins and 96 metabolites that were differentially expressed in the DQ-treated mice relative to the control mice (p < 0.05), and showed significant enrichment in the PPAR signaling pathway and fatty acid metabolism. Hmgcs2, Cyp4a10, Cyp4a14 and Lpl were identified as the major proteins/genes associated with DQ-induced kidney damage. In addition, eicosapentaenoic acid, linoleic acid, palmitic acid and (R)-3-hydroxybutyric acid were the major metabolites related to DQ-induced kidney injury. Overall, the multi-omics analysis showed that DQ-induced kidney damage is associated with dysregulation of the PPAR signaling pathway, and an aberrant increase in Hmgcs2 expression and 3-hydroxybutyric acid levels. Our findings provide new insights into the molecular basis of DQ-induced early kidney damage.

Funder

National Natural Science Foundation of China

Key Clinical Specialty Project

Young Scholars Fostering Fund of the First Affiliated Hospital of Nanjing Medical University

Publisher

MDPI AG

Subject

Chemical Health and Safety,Health, Toxicology and Mutagenesis,Toxicology

Reference25 articles.

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3. Rapid Glomerulotubular Nephritis as an Initial Presentation of a Lethal Diquat Ingestion;Guck;Case Rep. Nephrol.,2021

4. A case of fatal diquat poisoning: Toxicokinetic data and autopsy findings;Hantson;J. Toxicol. Clin. Toxicol.,2000

5. Acute toxic kidney injury;Petejova;Ren. Fail.,2019

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