Description
This hepatotoxic alkaloid is widely distributed among the Senecio species, being found in S. aureus, S. ilicifolius Thunb., S. integerrirnus, S. pseudaarnica, S. squaUdus, S. viscosus and S. vulgaris. The base is laevorotatory with [α]
D - 54.6° (CHCI
3 ) and the crystals sublime at 130-140°CfO.2 mm. The nitrate has m.p. 214°C;[α]
D - 34.2° (H
2 0); the aurichloride, m.p. 186°C; the picrate, m.p. 191°C and the methiodide, m.p. 249°C. Alkaline hydrolysis furnishes retronecine and senecic acid (6-hydroxy-5-methyl-2-heptene-3 :6-dicarboxylic acid).
Description
Senecionine is a pyrrolizidine alkaloid that has been found in
S. vulgaris and has hepatotoxic properties. 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. Senecionine (20 μM) induces mitochondrial depolarization and fragmentation in primary cultured mouse hepatocytes and increases apoptosis in a concentration-dependent manner. 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. Senecionine-induced hepatotoxicity is associated with lipid peroxidation and glutathione depletion.
Uses
Senecionine is a pyrrolizidine alkaloid with the potential to affect hepatic drug metabolizing enzymes in rat cells.
Definition
ChEBI: A pyrrolizidine alkaloid isolated from the plant species of the genus Senecio.
Safety Profile
Poison by intravenous,intraperitoneal, and possibly other routes. Anexperimental teratogen. Other experimental reproductiveeffects. Mutation data reported. When heated todecomposition it emits toxic fumes of NOx.
References
Grandval, Lajoux., Cornpt. rend., 120,1120 (1895)
Grandval, Lajoux., Bull. Soc. Chirn. Fr., 13,942 (1895)
Manske., Can. J. Res., S, 651 (1931)
Manske., ibid, 14B, 6 (1936)
Barger, Blackie., J. Chern. Soc., 584 (1937)
Blackie., Pharrn. J., 138,102 (1937)
Manske., Can. J. Res., 17B, I (1939)
