PMID: 9182239Feb 1, 1996Paper

Physicochemical and metabolic basis for the differing neurotoxicity of the pyrrolizidine alkaloids, trichodesmine and monocrotaline

Neurochemical Research
R J HuxtableR Cooper

Abstract

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 mM of the parent PA. Dehydrotrichodesmine had a significantly longer aqueous half-life (5.4 sec) than that of dehydromonocrotaline (3.4 sec). In vivo, significantly higher levels of bound pyrroles were found in the brain 18 hr after injection of trichodesmine (25 mg/kg; i.p.) than were seen following either an equal dose (25 mg/kg; i.p.) or an equitoxic dose (90 mg/kg; i.p.) of monocrotaline. Trichodesmine had a higher partition coefficient than monocrotaline for both chloroform and heptane, indic...Continue Reading

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Citations

Dec 18, 2008·BMC Pulmonary Medicine·Rio DumitrascuRalph T Schermuly
Dec 20, 2012·Oxidative Medicine and Cellular Longevity·José Eduardo Ribeiro HonórioSilvânia Maria Mendes Vasconcelos
Nov 1, 2009·Environmental Toxicology and Pharmacology·Ying ChenZhengtao Wang
Sep 26, 2015·Pulmonary Pharmacology & Therapeutics·Rita Nogueira-FerreiraTiago Henriques-Coelho
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Aug 9, 2006·Journal of Neurochemistry·Seok Jong HongKwang-Soo Kim
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Apr 25, 2019·PLoS Biology·Diddahally R Govindaraju
Sep 26, 2013·Journal of Immunoassay & Immunochemistry·Eunhye Kim, Insook Rhee Paeng
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Jun 6, 2020·Journal of Environmental Science and Health. Part C, Toxicology and Carcinogenesis·Zijing SongGe Lin
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May 19, 2021·Archives of Toxicology·Yisheng HeGe Lin

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