Study on the mechanism of brain injury caused by acute diquat poisoning based on metabolomics.

Abstract

Brain injury following acute diquat poisoning has become increasingly common in moderate to severe cases, with unclear pathogenesis and high mortality. To investigate this, we conducted metabolomics on brain tissue from poisoned rats, combined with clinical biochemical and pathological analyses. In the high-dose group, 24 metabolites showed significant differences compared to the control group: 18 were upregulated, including cytosine, sedoheptulose-7-phosphate, indole, 3-dehydroshikimate, etc.; 6 were downregulated, including 6-phosphogluconic acid, 3-hydroxybenzoic acid, dAMP, etc. In the low-dose group, 10 metabolites showed significant differences: 4 were upregulated, including pentamidine, γ-tocotrienol, benzoylecgonine, etc.; and 6 were downregulated, including dAMP, glutathione, 3-hydroxybenzoic acid, etc. Enrichment analysis identified two key pathways-phenylalanine, tyrosine, and tryptophan biosynthesis, and the pentose phosphate pathway-as involved in brain injury. ROC analysis of six differential metabolites showed that sedoheptulose-7-phosphate, (2R)-2-hydroxy-3-(phosphonatooxy)propanoate, and 3-hydroxybenzoic acid had AUC values above 0.8. These findings suggest that these three metabolites demonstrate strong diagnostic potential for brain injury induced by diquat poisoning. Correlation analysis linked these biomarkers to clinical indicators such as neutrophil count and the eutrophil to lymphocyte ratio, supporting their relevance. This study provides insights into the mechanisms and biomarkers of diquat-induced brain injury, offering a foundation for future treatment and rapid detection.