Pyrrolizidine alkaloids poisonings

Pyrrolizidine alkaloid poisoning continues to be a significant problem in the U.S. and throughout the world, and is a focus of research at the USDA Poisonous Plant Research Laboratory. 

Hooper, P. T. 1978. Pyrrolizidine alkaloid poisoning-pathology with particular reference to differences in animal and plant species. In Effects of Poisonous Plants on Livestock (KqqIqt, R. F., Van Kampen, K. R. and James, L.F., eds), pp. 161-176. New York Academic Press. 

Knight, A. P., Kimberling, C. V., Stermitz, E. R. and Roby, M. R. 1984. Cynoglossum officinale (Hound s tongue) - A case of pyrrolizidine alkaloid poisoning in horses. Journal of American Veterinary Medicine Association, 185 647-650. 

In Austria an 18-month-old boy became III and was taken to hospital, where he was found to have liver disease of the type charaoteristio of pyrrolizidine alkaloid poisoning. He had been given herbal tea since he was 3 months old. The herbal tea should have been been made with the plant ooltsfoot but was mistakenly made with alpendost. The boy had congestion of the blood vessels of the liver (veno-ooclusive disease) whioh were also damaged and bleeding. ... 

Trichodesma incanum which grows in central Asia is responsible for suiljuk, a condition in cattle and horses which appears to be similar to seneciosis. Certain Cynoglossum spp. have also been shown to contain pyrrolizidine alkaloids. Poisoning of cattle by C. officinale has been reported (39), but it is not clear whether the alkaloids are implicated. 

The protective effects of zinc, butylated hydroxyanisole, ethoxyquin,and disulphiram against pyrrolizidine alkaloid poisoning in rats and mice have been studied. Disulphiram was... 

In connection with the toxicity of the pyrrolizidine alkaloids the toxic effects of the alkaloids themselves have been reproduced by dosing experimental animals with synthetic compounds. Because the most toxic alkaloids are esters which are resistant to enzymic hydrolysis, and which are converted in vivo into pyrrole derivatives, it was expected that simpler pyrroline esters would prove to exhibit the same toxic properties as the alkaloids. This expectation was realised when it was shown that the dicarbamate (59) is rather more toxic than monocrotaline, and further that the tissue damage produced is histologically similar to that observed in cases of pyrrolizidine alkaloid poisoning. A compound of slightly lesser toxicity is the retronecine derivative (60). 

Other significant experiments have corroborated the metabolic pyrrole hypothesis. When cells other than those capable of microsomal oxidation (i.e., cells other than liver) were incubated with pyrrolizidine alkaloids toxicity was not observed. However when these cells were exposed to synthetically prepared necine pyrroles, severe mitotic inhibition was observed. The chemical stability of the pyrrolic alkaloids is much less than that of the corresponding necine pyrroles and the former have not been detected Ija vivo. However when synthetic monocrotaline pyrrole was injected into the mesenteric vein of rats it produced the lesions typical of pyrrolizidine alkaloid poisoning portal vascular degeneration, hepatic necrosis, and inhibition of hepatocyte mitosis (63,64). Injected into the jugular veins of rats and dogs... 

Huxtable, R.J. 1987. Pyrrolizidine alkaloid poisoning in the United States [abstract]. Pharmacologist 29(3) 155. 

Pyrrolizidine alkaloids poison animals grazing on toxic wild plants and those fed contaminated feed, causing economic losses. They poison humans through deliberate consumption of certain foods and herbal medicines and through consumption of food contaminated by wild plants, such as via transport of the toxins by bees into honey. Analytical methods are required for different purposes - to detect the presence of pyrrolizidine alkaloids, to quantify the total level of the toxins, or to measure the quantity of individual compounds. The task is made more challenging by the variety of PAs, their widespread nature and their different forms. Analytical methods are based on color reactions, enzyme linked immunosorbent assays (ELlSAs), spectroscopy, and the full range of chromatographic techniques. A lack of reference standards and... 

Loss of livestock due to pyrrolizidine alkaloid poisoning is a growing economic problem. The effects of these alkaloids on animals was discussed at a recent symposium (750). An outbreak of chicken poisoning in Australia was caused by food containing seeds of Heliotropium europaeum 220). The toxicity of a range of pyrrolizidine esters on rats has been studied 81). 

We knew Utetheisa to feed on poisonous plants as a larva (Figure 1B). The plants, of the genus Crotalaria (family Leguminosae), were known to contain pyrrolizidine alkaloids (henceforth abbreviated as PAs), intensely bitter compounds potently hepatotoxic to mammals (7). Other species of Utetheisa were known to sequester PAs (8). We found this to be true for U. ornatrix as well. Adult Utetheisa raised on Crotalaria spectabilis, one of the principal foodplants available to the moth in the United States, contain on average about 700 p,g of monocrotaline (1), the principal PA in that plant (9, 10). 

Many pyrrolizidine alkaloids are known to produce pronounced hepatic toxicity and there are many recorded cases of livestock poisoning. Potentially toxic structures have 1,2-unsaturation in the pyrrolizidine ring and an ester function on the side-chain. Although themselves non-toxic, these alkaloids are transformed by mammalian liver... 

Pyrrolizidine alkaloids in the plant Senecio vernalis have been implicated in the poisoning of cattle.13 The toxic agents in this plant include three closely related alkaloids — senecionine, senkirkin, and seneciphyllin. The structural formula of senecionine is shown in Figure 19.2. 

Pterophorine and inaequidenine, two other dihydropyrrolizinone alkaloids, were previously isolated from Senecio inaequidens DC. (cf. Vol. 8, pp. 54-56). Senecionine and retrorsine have now also been shown to be present in this species.31,32 7-Angelylheliotridine (43) has been isolated from S. ovirensis ssp. gaudinii.32,33 The cause of poisoning in dairy cattle in Switzerland was found to be S. alpinus.34 Nine known pyrrolizidine alkaloids were isolated from this species, and the major constituent was seneciphylline. Otosenine, floridanine, and doronine are present in 5. othonnae.35 The extraction of seneciphylline and platyphylline from S. platyphylloides has been studied by a variety of methods.36... 

The most toxic plant product, ricin, is also the most toxic chemical known to man. Unlike the pyrrolizidine alkaloids, ricin is a protein which most cleverly targets the interior workings of cells. The way in which this most potent poison works is quite elegant (see box, p. 151). It is made and found in the seeds of the castor bean (Ricinus communis). 

There is no evidence of pyrrolizidine alkaloids in Eupatorium rugosum (white snakeroot) but this plant also has poisonous properties, which are attributed to an unstable toxin called tremetol. Transfer from cow s milk to humans can produce a condition known as milk sickness, including trembles, weakness, nausea and vomiting, prostration, delirium, and even death. 

When a family of toxins is weUknown, like the pyrrolizidine alkaloids [1], it is highly interesting to screen suspected plants for their presence when poisoning is suspected in animals and there may be some residues in food, even in animals which did not present any disorder. 

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