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Physicochemical And Metabolic Basis For The Differing Neurotoxicity Of The Pyrrolizidine Alkaloids, Trichodesmine And Monocrotaline, R. J. Huxtable, C. C. Yan, S. Wild, S. Maxwell, Roland Cooper
Physicochemical And Metabolic Basis For The Differing Neurotoxicity Of The Pyrrolizidine Alkaloids, Trichodesmine And Monocrotaline, R. J. Huxtable, C. C. Yan, S. Wild, S. Maxwell, Roland Cooper
Roland A. Cooper
Monocrotaline and trichodesmine are structurally closely related pyrrolizidine alkaloids (PAs) exhibiting different extrahepatic toxicities, trichodesmine being neurotoxic (LD(50) 57 mu mol/kg) and monocrotaline pneumotoxic (LD(50) 335 mu mol/kg). We have compared certain physicochemical properties and metabolic activities of these two PAs in order to understand the quantitative and qualitative differences in toxicity. Both PAs were metabolized in the isolated, perfused rat liver to highly reactive pyrrolic dehydroalkaloids that appear to be responsible for the toxicity of PAs. More dehydrotrichodesmine (468 nmol/g liver) than dehydromonocrotaline (116 nmol/g liver) was released from liver into perfusate on perfusion for 1 hr with 0.5 …