Pyrrolizidine alkaloid

Pyrrolizidine alkaloids (PAs), sometimes referred to as necine bases, are a group of naturally occurring alkaloids based on the structure of pyrrolizidine. Pyrrolizidine alkaloids are produced by plants as a defense mechanism against insect herbivores. More than 660 PAs and PA N-oxides have been identified in over 6,000 plants, and about half of them exhibit hepatotoxicity.[1] They are found frequently in plants in the Boraginaceae, Asteraceae, Orchidaceae and Fabaceae families; less frequently in the Convolvulaceae and Poaceae, and in at least one species in the Lamiaceae. It has been estimated that 3% of the world’s flowering plants contain pyrrolizidine alkaloids.[2] Honey can contain pyrrolizidine alkaloids,[3][4] as can grains, milk, offal and eggs.[5] To date (2011), there is no international regulation of PAs in food, unlike those for herbs and medicines.[6][7]

Skeletal formula of retronecine, a pyrrolizidine alkaloid found in the common groundsel (Senecio vulgaris) and comfrey (Symphytum spp.)

Unsaturated pyrrolizidine alkaloids are hepatotoxic, that is, damaging to the liver.[8][9] PAs also cause hepatic veno-occlusive disease and liver cancer.[10] PAs are tumorigenic.[11] Disease associated with consumption of PAs is known as pyrrolizidine alkaloidosis.

In humans, the use of medicinal herbs containing PAs, notably borage leaf, comfrey and coltsfoot in the West, and some Chinese medicinal herbs, has been shown to pose health risks.[11] The degree of toxicity can vary based on age and gender, with fetuses and neonates showing high sensitivity, including instances of death. [12]

Some ruminant animals, for example cattle, show no change in liver enzyme activities or any clinical signs of poisoning when fed low concentrations of plants containing pyrrolizidine alkaloids.[13] Yet, Australian studies have demonstrated toxicity.[14] Sheep and goats especially, and to a lesser degree cattle, are much more resistant and tolerate much higher PA dosages, thought to be due to thorough detoxification via PA-destroying rumen microbes. [12]

PA is also used as a defense mechanism by some organisms such as Utetheisa ornatrix. Utetheisa ornatrix caterpillars obtain these toxins from their food plants and use them as a deterrent for predators. PAs protect them from most of their natural enemies. The toxins stay in these organisms even when they metamorphose into adult moths, continuing to protect them throughout their adult stage.[15]

Ecology
Main article: Pyrrolizidine alkaloid sequestration

Many plants contain pyrrolizidine alkaloids, and in turn there are many insects which consume the plants and build up the alkaloids in their bodies.[16] For example, male queen butterflies utilize pyrrolizidine alkaloids to produce pheromones useful for mating.[17] The butterfly Danaus chrysippus is known to obtain pyrrolizidine alkaloids in their diet and store these chemicals, making them toxic and unpalatable to predators.[18] Greta oto, the glasswing butterfly, uses pyrrolizidine alkaloids for both toxicity in the adult moth and pheromone production in the male butterfly. The garden tiger moth also stores these compounds as a caterpillar, using them for larval (through the use of spines) and adult defense (in the form of a spray and bad taste).[19]

Plants species containing pyrrolizidine alkaloids

The effect of PAs in humans, that is PAILDs (Pyrrolizidine Alkaloid Induced Liver Diseases),[28] of epidemic proportions was recorded after a long field-level epidemiological investigation in the northern region of Ethiopia-Tigray.[29]

Classification

One classification is based on the substitution pattern of the pyrrolizidine ring. This part of the structure is normally referred to as necine bases. The three largest groups are based on the three necine bases platynecine, heliotridine and retronecine.

  • Platynecine
    Platynecine
  • Heliotridine
    Heliotridine
  • Retronecine
    Retronecine

References
  1. Radominska-Pandya, A (2010). "Invited Speakers". Drug Metabolism Reviews. 42 (S1): 1–2. doi:10.3109/03602532.2010.506057. PMID 20842800.
  2. Smith, L. W.; Culvenor, C. C. J. (1981). "Plant sources of hepatotoxic pyrrolizidine alkaloids". J. Nat. Prod. 44 (2): 129–15. doi:10.1021/np50014a001. PMID 7017073.
  3. Kempf, M; Reinhard, A; Beuerle, T (Jan 2010). "Pyrrolizidine alkaloids (PAs) in honey and pollen-legal regulation of PA levels in food and animal feed required". Mol Nutr Food Res. 54 (1): 158–68. doi:10.1002/mnfr.200900529. PMID 20013889.
  4. Edgar, John A.; Roeder, Erhard; Molyneux, Russell J. (2002). "Honey from Plants Containing Pyrrolizidine Alkaloids: A Potential Threat to Health". J. Agric. Food Chem. 50 (10): 2719–2730. doi:10.1021/jf0114482. PMID 11982390.
  5. "Pyrrolizidine alkaloids in Food" (PDF). Archived from the original (PDF) on 2009-10-14.
  6. Coulombe, Roger A. Jr (2003). "Pyrrolizidine alkaloids in foods". Advances in Food and Nutrition Research Volume 45. pp. 61–99. doi:10.1016/S1043-4526(03)45003-1. ISBN 9780120164455. PMID 12402679. {{cite book}}: |journal= ignored (help)
  7. German Commission E monographs
  8. "Foodborne Pathogenic Microorganisms and Natural Toxins Handbook: Pyrrolizidine Alkaloids". Bad Bug Book. United States Food and Drug Administration. Retrieved 2009-07-11.
  9. Schoental, R.; Kelly, JS (April 1959). "Liver lesions in young rats suckled by mothers treated with the pyrrolizidine (Senecio) alkaloids, lasiocarpine and retrorsine". The Journal of Pathology and Bacteriology. 77 (2): 485–495. doi:10.1002/path.1700770220. PMID 13642195.
  10. Schoental, R (1968). "Toxicology and Carcinogenic Action of Pyrrolizidine Alkaloids" (PDF). Cancer Research. 28 (11): 2237–2246. PMID 4302035.
  11. Fu, P.P.; Yang, Y.C.; Xia, Q.; et al. (2002). "Pyrrolizidine alkaloids-tumorigenic components in Chinese herbal medicines and dietary supplements". {{cite journal}}: Cite journal requires |journal= (help)
  12. Wiedenfeld, H.; Edgar, J. (2011). "Toxicity of pyrrolizidine alkaloids to humans and ruminants". Phytochemistry Reviews. 2010 (1): 1–15. Bibcode:2011PChRv..10..137W. doi:10.1007/s11101-010-9174-0. S2CID 36631492.
  13. Skaanild, M.T.; Friis, C.; Brimer, L. (2001). "Interplant alkaloid variation and Senecio vernalis toxicity in cattle". Veterinary and Human Toxicology. 43 (3): 147–151. PMID 11383654.
  14. Noble, J.W.; Crossley, J.; Hill, B.D.; et al. (1994). "Pyrrolizidine alkaloidosis of cattle associated with Senecio lautus". Australian Veterinary Journal. 71 (7): 196–200. doi:10.1111/j.1751-0813.1994.tb03400.x. PMID 7945096.
  15. Conner, W.E. (2009). Tiger Moths and Woolly Bears: Behaviour, Ecology, and Evolution of the Arctiidae. New York: Oxford University Press. pp. 1–10. ISBN 9780195327373.
  16. Nishida, R; Schulz, S; Kim, C. S; et al. (1996). "Male sex pheromone of a giant danaine butterfly,Idea leuconoe". Journal of Chemical Ecology. 22 (5): 949–72. doi:10.1007/BF02029947. PMID 24227617. S2CID 23449117.
  17. Scott, James A. (1997). "Family Nymphalidae: Brush-Footed Butterflies". The Butterflies of North America: A Natural History and Field Guide. Stanford, California: Stanford University Press. pp. 228–232. ISBN 9780804720137.
  18. Edgar, J. A.; Cockrum, P. A.; Frahn, J. L. (1976-12-01). "Pyrrolizidine alkaloids inDanaus plexippus L. and Danaus chrysippus L.". Experientia. 32 (12): 1535–1537. doi:10.1007/bf01924437. ISSN 0014-4754. S2CID 27664625.
  19. Macel, Mirka (2011-03-01). "Attract and deter: a dual role for pyrrolizidine alkaloids in plant–insect interactions". Phytochemistry Reviews. 10 (1): 75–82. Bibcode:2011PChRv..10...75M. doi:10.1007/s11101-010-9181-1. ISSN 1568-7767. PMC 3047672. PMID 21475391.
  20. Wiedenfeld, H; Andrade-Cetto, A (2001). "Pyrrolizidine alkaloids from Ageratum houstonianum Mill". Phytochemistry. 57 (8): 1269–71. Bibcode:2001PChem..57.1269W. CiteSeerX 10.1.1.576.4086. doi:10.1016/S0031-9422(01)00192-3. PMID 11454357.
  21. Broch-Due, Å. I.; Aasen, A. J. (1980). "Alkaloids of Anchusa officinalis L. Identification of the Pyrrolizidine Alkaloid Lycopsamine". Acta Chem. Scand. B34: 75–77. doi:10.3891/acta.chem.scand.34b-0075.
  22. "TABLE 05: Important Poisonous Vascular Plants of Australia". The Merck Veterinary Manual. Archived from the original on 2010-11-17.
  23. Connor Yearsley. "American Herbal Pharmacopoeia Publishes Boneset Monograph and Therapeutic Compendium". HerbalGram. American Botanical Council. 125: 26–28.
  24. Wood, Matthew. "The Book of Herbal Wisdom: Using Plants As Medicines." Berkeley CA. North Atlantic Books. 1997.
  25. Kakar F, Akbarian Z, Leslie T, et al. (28 Jun 2010). "An outbreak of hepatic veno-occlusive disease in Western afghanistan associated with exposure to wheat flour contaminated with pyrrolizidine alkaloids". J Toxicol. 2010: 313280. doi:10.1155/2010/313280. PMC 2905904. PMID 20652038.
  26. Rizk A. M. (1990). "The Pyrrolizidine Alkaloids: Plant Sources and Properties". Naturally Occurring Pyrrolizidine Alkaloids. CRC Press. p. 12. ISBN 0849346509.
  27. Yeong M. L.; et al. (1990). "Hepatic veno-occlusive disease associated with comfrey ingestion". Journal of Gastroenterology and Hepatology. 5 (2): 211–214. doi:10.1111/j.1440-1746.1990.tb01827.x. PMID 2103401. S2CID 42511497.
  28. "Pyrrolizidine Alkaloid Induced Liver Diseases", cited in Chiu, C; Buttke, D; Welde, G; et al. (2013). "Evaluation of the Pyrrolizidine Alkaloid Induced Liver Disease (PAILD) Active Surveillance System in Tigray, Ethiopia". Online Journal of Public Health Informatics. 5 (1): e167. doi:10.5210/ojphi.v5i1.4560. PMC 3692817.
  29. "Investigating Liver disease in Ethiopia". National Center for Environmental Health. CDC. 30 Oct 2012.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.