Mechanisms for Pyrrolizidine Alkaloid Activation and Detoxification

  • Donald R. Buhler
  • Cristobal L. Miranda
  • Bogdan Kedzierski
  • Ralph L. Reed
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)


The pyrrolizidine alkaloids (PAs) constitute a large group of hepatotoxic and carcinogenic plant constituents of wide geographic and botanical distribution. These alkaloids are responsible for the death of livestock throughout the world and for occasional human poisonings following the consumption of contaminated foods or the injudicious use of herbal medicines (Bull et al., 1968; Mattocks, 1986; Hirano, 1981; Huxtable, 1980; Peterson and Culvenor, 1983). PAs are relatively nontoxic but are bioactivated in vivo primarily via the liver, through enzymatic dehydrogenation to form highly reactive pyrrole- type metabolites. It is thought that PAs are initially converted to the corresponding dehydropyrrolizidine alkaloids (PA pyrroles) which then can either alkylate protein, DNA or other cellular nucleophiles (Hsu et al. 1975; Reed et al. 1988; Wickramanayake et al., 1985) or be hydrolyzed to the more stable pyrrolic alcohol, such as (R)-6,7-dihydro-7-hydroxy-l-hydroxymethy1-5H-pyrrolizidine (DHP) in the case of retronecine or heliotridine based PAs (Jago et al., 1979; Kedzierski and Buhler, 1985, 1986; Mattocks, 1986; Mattocks and White, 1971). PAs also can be oxidized in vivo to relatively nontoxic PA N-oxides and hydrolyzed to the corresponding amino alcohol (Kedzierski and Buhler, 1986; Mattocks, 1986; Ramsdell et al., 1987).


Fast Atom Bombardment Pyrrolizidine Alkaloid Fast Atom Bombardment Spectrum Enzymatic Dehydrogenation Pyrrolic Metabolite 
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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Donald R. Buhler
    • 1
    • 2
  • Cristobal L. Miranda
    • 2
  • Bogdan Kedzierski
    • 2
  • Ralph L. Reed
    • 2
  1. 1.Toxicology ProgramOregon State UniversityCorvallisUSA
  2. 2.Department of Agricultural ChemistryOregon State UniversityCorvallisUSA

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