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Toxins 2016, 8(12), 356; doi:10.3390/toxins8120356

Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

1
United States Department of Agriculture, Agriculture Research Service, Poisonous Plant Research Laboratory, 1150 East 1400 North, Logan, UT 84341, USA
2
Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA
3
United States Army Institute of Surgical Research, Ft Sam Houston, TX 78234, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Jia-You Fang
Received: 1 October 2016 / Revised: 22 November 2016 / Accepted: 24 November 2016 / Published: 29 November 2016
(This article belongs to the Collection Toxicity of Natural Alkaloids)
View Full-Text   |   Download PDF [3762 KB, uploaded 29 November 2016]   |  

Abstract

Dehydropyrrolizidine alkaloid (DHPA)-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health. View Full-Text
Keywords: dehydropyrrolizidine; DHPA; pyrrolizidine; alkaloids; PA; toxic plant; pyrrolizidine alkaloid-induced cytotoxicity; toxic hepatopathy; carcinogenesis dehydropyrrolizidine; DHPA; pyrrolizidine; alkaloids; PA; toxic plant; pyrrolizidine alkaloid-induced cytotoxicity; toxic hepatopathy; carcinogenesis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Stegelmeier, B.L.; Colegate, S.M.; Brown, A.W. Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity. Toxins 2016, 8, 356.

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