Senecionine is a pyrrolizidine alkaloid that has been found in S. vulgaris and has hepatotoxic properties.1 It is metabolized by the cytochrome P450 (CYP) isoform CYP3A in the liver to the detoxification product senecionine N-oxide and reactive metabolites including dehydropyrrolizidine alkaloids and dehydrotetronecine.2,3 Senecionine (20 μM) induces mitochondrial depolarization and fragmentation in primary cultured mouse hepatocytes and increases apoptosis in a concentration-dependent manner.2 In rats, senecionine (35 mg/kg, p.o.) induces liver injury, increases serum levels of bilirubin and various bile acids, including taurocholic acid, glycocholic acid, and deoxycholic acid, and increases the activity of alanine aminotransferase and aspartate aminotransferase in serum.1 Senecionine-induced hepatotoxicity is associated with lipid peroxidation and glutathione depletion.
1.Xiong, A., Yang, F., Fang, L., et al.Metabolomic and genomic evidence for compromised bile acid homeostasis by senecionine, a hepatotoxic pyrrolizidine alkaloidChem. Res. Toxicol.27(5)775-786(2014) 2.Yang, X., Wang, H., Ni, H.-M., et al.Inhibition of Drp1 protects against senecionine-induced mitochondria-mediated apoptosis in primary hepatocytes and in miceRedox Biol.12264-273(2017) 3.Miranda, C.L., Reed, R.L., Guengerich, F.P., et al.Role of cytochrome P450IIIA4 in the metabolism of the pyrrolizidine alkaloid senecionine in human liverCarcinogenesis12(3)515-519(1991)