Pyrrolizidine Poisonings

HUXTABLE, R.J., Herbal teas and toxins novel aspects of pyrrolizidine poisoning in the United States., Perspect. Biol. Med., 1980,24, 1-14. 

V Stenkamp, M. J. Stewart, and M. Zuckerman, Clinical and analytical aspeas of pyrrolizidine poisoning caused by South African traditional medicines , Therapeutic Drug Monitoring, 22 (2000), 302. 

Outbreaks of pyrrolizidine poisonings in humans have occurred and have generally been associated with contaminated grain used for meal or bread. The pyrrolizidines have also been detected in comfrey teas (Roitman, 1981) commonly available at herbal medicine and health food stores. The possibility of the occurrence of pyrrolizidine residues in meat or milk of livestock consuming toxic plants exists, but no toxic responses in humans from this source has been reported (Peterson and Culvenor, 1983). 

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). 

In an effort to identify possible sources of the 16 alkaloids found in the skin of the Panamanian poison frog Dendrobates auratus, ants from a total of 61 terrestrial nests were analyzed [124]. The alate queens of one species of myr-micine ants (Solenopsis (Diplorhoptrum) sp.) collected at Cerro Ancon were found to contain the decahydroquinoline (-)-ds-195A (112) which was also present as a minor alkaloid in the skin of the microsympatric population of D. auratus. Moreover, from wingless ants of two nests collected at Isla Taboga and identified as Megalomyrmex silvestrU the same workers isolated the stereo-isomeric 3,5-disubstituted pyrrolizidines rfs-251 K (117) and trans-251 K (118) in the same ratio 3 1 that was present in the skin of a microsympatric population of D. auratus (Fig. 20) [124]. 

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. 

This compound exhibits the same relationship to (3-D-fructofuranose as 1-deoxy-nojirimcin does to D-glucopyranose. In 1979, a polyhydroxyindolizidine alkaloid was isolated from the poisonous fruit of Castanospermum australe, a handsome Australian indigenous tree, and coined castanospermine (8) after its source.28 A compound subsequently isolated from the seeds of this plant was the pyrrolizidine australine (9),29 also found in Alexa leiopetala,30 along with other compounds. These discoveries increasingly supported the hypothesis that imino sugars and their structural relatives might be a fairly common family of natural products, and their widespread... 

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. 

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... 

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. ... 

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. 

---