Dehydropyrrolizidine alkaloid toxicity, cytotoxicity, and carcinogenicity

Authors: Stegelmeier, Bryan; Colegate, Steven; BROWN, AMMON - United States Army Institute Of Surgical Research

Submitted to: Toxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/24/2016
Publication Date: 11/29/2016
Citation: Stegelmeier, B.L., Colegate, S.M., Brown, A.W. 2016. Dehydropyrrolizidine alkaloid toxicity, cytotoxicity, and carcinogenicity. Toxins. 8:356. doi:10.3390/toxins8120356.

Interpretive Summary: Plant toxins called pyrrolizidine alkaloids (PAs) are found in plants that compose about 5% of the world’s flowering plants and they commonly poison livestock, wildlife and humans. Previous work has produced considerable understanding of PA poisoning. Intoxication is generally caused by contaminated grains, feed, flour and breads that result in acute, severe, short duration poisoning. Such severe poisoning produces characteristic liver lesions and the diagnosis is confirmed microscopically, epidemiologically, and chemically. Less is known about chronic poisoning as is likely to occur when plant populations are sporadic; when they are used as teas or herbal preparations; or when traces contaminate milk, honey, pollen or other animal products. Such subclinical exposures may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low PA doses of short durations. These concerns have moved some governments to prohibit or limit human PA exposure. The purpose of this review is to summarize recent PA research, compare this with in vitro and in vivo PA toxicity and carcinogenicity reports and summarize the implications of these findings on human and animal health.

Technical Abstract: Dehyro-pyrrolizidine alkaloid (PA)-containing plants compose about 5% of the world’s flowering plants and they commonly poison livestock, wildlife and humans. Previous work has produced considerable understanding of PA toxicity, species susceptibility, conditions and routes of exposure, toxin metabolism and clearance 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 as is likely to occur when plant populations are sporadic; when they are used as tisanes or herbal preparations; or when traces contaminate milk, honey, pollen or other animal products. Such subclinical exposures may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low PA doses of short durations. These concerns have moved some governments to prohibit or limit human PA exposure. The purpose of this review is to summarize recent PA research, compare this with in vitro and in vivo PA toxicity and carcinogenicity reports and summarize the implications of these findings on human and animal health.