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Metabolomics analysis of the potential toxicological mechanisms of diquat dibromide herbicide in adult zebrafish (Danio rerio) liver

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Abstract

Although diquat is a widely used water-soluble herbicide in the world, its sublethal adverse effects to fish have not been well characterised. In this study, histopathological examination and biochemical assays were applied to assess hepatotoxicity and combined with gas chromatography–mass spectrometry (GC–MS)-based metabolomics analysis to reveal overall metabolic mechanisms in the liver of zebrafish (Danio rerio) after diquat exposure at concentrations of 0.34 and 1.69 mg·L−1 for 21 days. Results indicated that 1.69 mg·L−1 diquat exposure caused cellular vacuolisation and degeneration with nuclear abnormality and led to the disturbance of antioxidative system and dysfunction in the liver. No evident pathological injury was detected, and changes in liver biochemistry were not obvious in the fish exposed to 0.34 mg·L−1 diquat. Multivariate statistical analysis revealed differences between profiles obtained by GC–MS spectrometry from control and two treatment groups. A total of 17 and 22 metabolites belonging to different classes were identified following exposure to 0.34 and 1.69 mg·L−1 diquat, respectively. The metabolic changes in the liver of zebrafish are mainly manifested as inhibition of energy metabolism, disorders of amino acid metabolism and reduction of antioxidant capacity caused by 1.69 mg·L−1 diquat exposure. The energy metabolism of zebrafish exposed to 0.34 mg·L−1 diquat was more inclined to rely on anaerobic glycolysis than that of normal zebrafish, and interference effects on lipid metabolism were observed. The metabolomics approach provided an innovative perspective to explore possible hepatic damages on fish induced by diquat as a basis for further research.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant numbers [31902418]), the Natural Science Foundation of Hainan Province (Grant numbers [319QN160]), and the Research Initiation Fund Project of Hainan University (Grant numbers [KYQD(ZR)19108]).

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  1. Ye Xiao and Xiang Lin contributed equally to this work and shared first authorship.

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  1. School of Pharmaceutical Sciences, Hainan University, 58 Renmin Rd, Haikou, 570228, People’s Republic of China

    Ye Xiao, Xiang Lin, Meilan Zhou, Tianyu Ren, Ruili Gao, Zhongqun Liu, Wenjing Shen, Rong Wang, Xi Xie, Yanting Song & Wenting Hu

  2. Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, 58 Renmin Rd, Haikou, 570228, People’s Republic of China

    Ye Xiao, Xiang Lin, Meilan Zhou, Tianyu Ren, Ruili Gao, Zhongqun Liu, Wenjing Shen, Rong Wang, Xi Xie, Yanting Song & Wenting Hu

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Contributions

YX and XL performed the experiment, wrote the manuscript and contributed equally to this work; MZ, TR and RG participated in the performance of the experiments and critical revision; ZL contributed to manuscript preparation; WS did the initial analysis of the data; RW, XX and YS helped perform the analysis with constructive discussions; WH contributed to the conception of the study. All authors read and approved the final manuscript.

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Correspondence to Wenting Hu.

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Xiao, Y., Lin, X., Zhou, M. et al. Metabolomics analysis of the potential toxicological mechanisms of diquat dibromide herbicide in adult zebrafish (Danio rerio) liver. Fish Physiol Biochem 48, 1039–1055 (2022). https://doi.org/10.1007/s10695-022-01101-4

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