Nux Vomica Exposure Triggered Liver Injury and Metabolic Disturbance in Zebrafish Larvae

Zebrafish larvae were used to further understand the liver toxicity of nux vomica. The histopathology, protein expression, and gene expression were assessed to confirm apoptosis in the liver, and then, profiles of the metabolites in zebrafish were investigated by untargeted metabolomic assessment to understand the potential toxicity mechanism of nux vomica. Histopathological observations showed that nux vomica caused damage to liver cells. Western blot results indicated increased expression of activated caspase3, and the result of real-time polymerase chain reaction showed a significant increase in the expression level of caspase-3, caspase-8, and caspase-9 genes (p < 0.05) compared with the control group. The liver injury from nux vomica was linked to the downregulation of amino acid (e.g., proline and alanine) and fatty acid (e.g., palmitoleic acid) metabolism and upregulation of some other fatty acid (e.g., arachidic acid) and purine (e.g., xanthine and uric acid) metabolism. The hepatotoxicity of nux vomica resulted from metabolic pathway disturbances, including small molecules involved in energy, purine, lipids, and amino acid metabolism.