page_title: Senecionine
section_title: Metabolism and Mechanism of Action
hierarchical_section_title: Senecionine / Metabolism and Mechanism of Action
caption_attribution_description: English: Senecionine metabolism
context_page_description: Senecionine is a toxic pyrrolizidine alkaloid isolated from various botanical sources. It takes its name from the Senecio genus and is produced by many different plants in that genus, including Jacobaea vulgaris. It has also been isolated from several other plants, including Brachyglottis repanda, Emilia, Erechtites hieraciifolius, Petasites, Syneilesis, Crotalaria, Caltha leptosepala, and Castilleja.
  The compound is toxic and consumption can lead to liver damage, cancer, and pyrrolizidine alkaloidosis. Because of this, consumption of plants that produce it has resulted in poisonings, both in humans and in animals.
context_section_description: After oral ingestion, senecionine is absorbed from the gastrointestinal tract. When it reaches the liver, it is metabolized via three pathways: N-oxidation, oxidation, and ester hydrolysis. N-oxidation and hydrolysis are detoxification pathways, and the products of these reactions are conjugated and excreted by the kidneys. However, the N-oxide may be converted back into senecionine by cytochrome P-450 (CYP450) monooxygenases. Oxidation of senecionine to its respective dehydropyrrolizidine is responsible for its toxic effects. 
  In the toxic pathway, the 2-pyrroline in the core is desaturated via an oxidation reaction to form a pyrrolic ester. This metabolite can still subsequently be eliminated if it is conjugated to glutathione. However, this metabolite is toxic because it can act as an electrophile. It may be attacked by either DNA base pairs or by amino acid residues in liver proteins, resulting in the formation of toxic adducts, including cross-linked adducts between DNA base pairs, liver proteins, or both. These adducts can damage DNA, leading to genotoxicity and carcinogenesis, and liver enzymes and hepatocytes, leading to hepatotoxicity.
caption: Metabolism and mechanism of action of pyrrolizidine alkaloid toxicity. Nuc=nucleophilic protein residue or DNA base[24]
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