Metabolomic analysis elucidates purine and amino acid as major toxicological biomarkers of triptolide in zebrafish

Triptolide exhibits significant toxicity. This study aims to investigate its toxicological biomarkers and metabolic pathways using a metabolomics approach in a zebrafish model. This study investigated toxicological biomarkers and metabolic pathways of triptolide in zebrafish exposed to 20, 180, or 360 ng/mL for 96 h. Untargeted UPLC-MS metabolomics revealed 3, 4, and 26 significantly altered metabolites in low‑, medium‑, and high‑dose groups, respectively. In the high‑dose group, acylcarnitines, glutamine, glutathione, inosine‑5'‑monophosphate (IMP), betaine, taurine, creatine, and hypoxanthine decreased, while glycerophosphocholine, deoxyguanosine, and 12‑hydroxyoctadecanoic acid increased. Pearson correlation identified guanine, deoxyguanosine, IMP, glycerophosphocholine, taurine, and oleoyl‑L‑carnitine as mortality‑correlated biomarkers. Pathway enrichment pointed to purine and amino acid metabolism. These findings provide a foundation for understanding triptolide's toxicological mechanisms.