title: Pyrrolizidine Alkaloids: Potential Role in the Etiology of Cancers, Pulmonary Hypertension, Congenital Anomalies, and Liver Disease.
abstract: Large outbreaks of acute food-related poisoning, characterized by hepatic sinusoidal obstruction syndrome, hemorrhagic necrosis, and rapid liver failure, occur on a regular basis in some countries. They are caused by 1,2-dehydropyrrolizidine alkaloids contaminating locally grown grain. Similar acute poisoning can also result from deliberate or accidental consumption of 1,2-dehydropyrrolizidine alkaloid-containing herbal medicines, teas, and spices. In recent years, it has been confirmed that there is also significant, low-level dietary exposure to 1,2-dehydropyrrolizidine alkaloids in many countries due to consumption of common foods such as honey, milk, eggs, salads, and meat. The level of 1,2-dehydropyrrolizidine alkaloids in these foods is generally too low and too intermittent to cause acute toxicity. However, these alkaloids are genotoxic and can cause slowly developing chronic diseases such as pulmonary arterial hypertension, cancers, cirrhosis, and congenital anomalies, conditions unlikely to be easily linked with dietary exposure to 1,2-dehydropyrrolizidine alkaloids, especially if clinicians are unaware that such dietary exposure is occurring. This Perspective provides a comprehensive review of the acute and chronic toxicity of 1,2-dehydropyrrolizidine alkaloids and their potential to initiate certain chronic diseases, and suggests some associative considerations or indicators to assist in recognizing specific cases of diseases that may have resulted from dietary exposure to these hazardous natural substances. If it can be established that low-level dietary exposure to 1,2-dehydropyrrolizidine alkaloids is a significant cause of some of these costly and debilitating diseases, then this should lead to initiatives to reduce the level of these alkaloids in the food chain.
authors.affiliation: CSIRO Food and Nutrition , 11 Julius Avenue, North Ryde, NSW 2113, Australia.
authors.forename: John A
authors.initials: JA
authors.lastname: Edgar
authors.affiliation: Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo , 34 Rainbow Drive, Hilo, Hawaii 96720, United States.
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Molyneux
authors.affiliation: Poisonous Plant Research Laboratory, ARS/USDA , 1150 East 1400 North, Logan, Utah 84341, United States.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Colegate
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D000013:Congenital Abnormalities / Q000209:etiology*; D005506:Food Contamination; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced*; D009369:Neoplasms / Q000139:chemically induced*; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*
chemical_list: D011763:Pyrrolizidine Alkaloids