Disease relevance of NSC30625

• Monocrotaline (MCT) is an 11-membered macrocyclic pyrrolizidine alkaloid (PA) that causes a pulmonary vascular syndrome in rats characterized by proliferative pulmonary vasculitis, pulmonary hypertension, and cor pulmonale [1].
• Monocrotaline (MCT) is a pyrrolizidine alkaloid (PA) plant toxin that produces sinusoidal endothelial cell (SEC) injury, hemorrhage, fibrin deposition, and coagulative hepatic parenchymal cell (HPC) oncosis in centrilobular regions of rat livers [2].
• The results suggested that there is not a strong correlation between the production of pyrrolic metabolites and susceptibility of animals to PA toxicity [3].
• Calves fed S riddellii to provide 10 mg of PA/kg of body weight/day in capsules or by gavage for 20 consecutive days did not develop clinical signs of seneciosis and did not have meaningful serum enzyme changes [4].
• The pyrrolizidine alkaloid (PA) monocrotaline (MCT) is thought to be activated in the liver to monocrotaline pyrrole (MCTP) which is then transported to the lungs where it causes a pulmonary vascular syndrome characterized by elevated pulmonary artery pressure and right ventricular hypertrophy [5].

High impact information on NSC30625

• The effect could be repeated using pure PAs fed to the insect in synthetic diets and by injection of PA into the hemolymph [6].
• Recently our laboratory isolated trans-4-OH-2-hexenal from the hepatic microsomal metabolism of the macrocyclic pyrrolizidine alkaloid (PA) senecionine and demonstrated in vivo that hepatic necrosis occurred following injection into the hepatic portal vein [7].
• The roles of cytochrome P450s and flavin-containing monooxygenases (FMO) in bioactivation and detoxification of pyrrolizidine alkaloids (PA) were studied in vitro using sheep and hamster hepatic microsomes [3].
• Monocrotaline is a pyrrolizidine alkaloid (PA) that causes a syndrome in rats that is a model for human primary pulmonary hypertension [8].
• The rate of PA activation in hamsters, a resistant species, measured by formation of (+/-)6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) far exceeded the rate of SN N-oxide formation (detoxification) (DHP/N-oxide = 2.29) [3].

Analytical, diagnostic and therapeutic context of NSC30625

• In addition, samples of ruminal fluid were separated by differential centrifugation under anaerobic conditions, and the resultant supernatants were tested for their ability to metabolize PA as compared with those of the respective uncentrifuged control fluids [9].
• Feeding activity by both herbivore species using a bioassay was inhibited up to circa 75% depending on PA and applied concentration [10].

References