Activation and pulmonary toxicity of pyrrolizidine alkaloids. 1990

R J Huxtable
Department of Pharmacology, College of Medicine, University of Arizona, Tucson 85724.

Pyrrolizidine alkaloids unsaturated in the 1,2 position are hepatotoxins. Certain of them, such as monocrotaline, are also pneumotoxins, producing pulmonary arterial hypertension and right ventricular hypertrophy as a delayed response two weeks after administration. Pneumotoxicity is the result of hepatic metabolism, the lung itself being unable to bioactivate pyrrolizidine alkaloids. The changes produced in the lung following exposure to pneumotoxic pyrrolizidine alkaloids are reviewed, together with the factors and interventions which modify or influence these changes. In the main, the earliest changes are seen in vascular smooth muscle and in the interactions between the smooth muscle and the endothelium. The search to identify the pneumotoxic metabolite is reviewed. It is generally accepted that pyrroles, or dehydroalkaloids, are responsible for the toxicity of pyrrolizidines. However, the primary pyrroles are intensely reactive, hydrolyzing and polymerizing within seconds in aqueous solution. Evidence for and against the pneumotoxin being a primary pyrrole or a stabilized secondary conversion product of a primary pyrrole is discussed.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D011763 Pyrrolizidine Alkaloids A group of ALKALOIDS, characterized by a nitrogen-containing necine, occurring mainly in plants of the BORAGINACEAE; COMPOSITAE; and LEGUMINOSAE plant families. They can be activated in the liver by hydrolysis of the ester and desaturation of the necine base to reactive electrophilic pyrrolic CYTOTOXINS. Pyrrolizidine Alkaloid,Senecio Alkaloid,Senecio Alkaloids,Alkaloid, Pyrrolizidine,Alkaloid, Senecio,Alkaloids, Pyrrolizidine,Alkaloids, Senecio
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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