Heliotropium europaeumPoisoning in Cattle and Analysis of Its Pyrrolizidine Alkaloid Profile

Abstract

Pyrrolizidine alkaloids (PAs) are carcinogenic and genotoxic phytochemicals found exclusively in angiosperms. The ingestion of PA-containing plants often results in acute and chronic toxicities in man and livestock, targeting mainly the liver. During February 2014, a herd of 15-18-month-old mixed-breed beef cattle (n = 73) from the Galilee region in Israel was accidently fed hay contaminated with 12% Heliotropium europaeum (average total PA intake was 33 mg PA/kg body weight/d). After 42 d of feed ingestion, sudden death occurred over a time period of 63 d with a mortality rate of 33%. Necropsy and histopathological examination revealed fibrotic livers and moderate ascites, as well as various degrees of hyperplasia and fibrosis of bile duct epithelial cells. Elevated γ-glutamyl-transferase and alkaline phosphatase levels were indicative of severe liver damage. Comprehensive PA profile determination of the contaminated hay and of native H. europaeum by LC-MS/MS revealed the presence of 30 PAs and PA-N-oxides, including several newly reported PAs and PA-N-oxides of the rinderine and heliosupine class. Heliotrine- and lasiocarpine-type PAs constituted 80% and 18% of the total PAs, respectively, with the N-oxides being the most abundant form (92%). The PA profile of the contaminated hay showed very strong resemblance to that of H. europaeum.

Occurrence of pyrrolizidine alkaloids in animal- and plant-derived food: results of a survey across Europe

“…Genera of each of these plant families such as Senecio, Eupatorium, Heliotropium, and Crotalaria have been reported as toxic to livestock and humans (Mohabbat et al 1976;Tandon et al 1976;Harper et al 1985;Hill et al 1997;Prakash et al 1999;Shimshoni et al 2015b;Kakar et al 2010).…”

Plant Alkaloids: Main Features, Toxicity, and Mechanisms of Action

“…The plant families Asteraceae, Boraginaceae, and Fabaceae often produce pyrrolizidine alkaloids (PAs), which are also ornithine-derived alkaloids, estimated to be present in more than 6,000 plants and known to be efficient against predators, including human and livestock (Shimshoni et al 2015). PAs' acute and chronic liver toxicity in humans and other animals is well known, and some symptoms of acute PA poisoning are abdominal pain, nausea, vomiting, diarrhea, and edema (Koleva et al 2012).…”

“…PAs' acute and chronic liver toxicity in humans and other animals is well known, and some symptoms of acute PA poisoning are abdominal pain, nausea, vomiting, diarrhea, and edema (Koleva et al 2012). Highly toxic carcinogenic and genotoxic effects are reported as the main mechanism of action of PAs (Shimshoni et al 2015). Food contaminated with PAs, mostly esters of 1-hydroxymethyl-1,2-dehydropyrrolizidine, include vegetables, grain-derived products, eggs, honey, offal, and milk, due to contamination of the grains by seeds and/or plant fragments from PA-containing weeds growing in the crops used for animal feeding or human consumption (Koleva et al 2012).…”

“…Food contaminated with PAs, mostly esters of 1-hydroxymethyl-1,2-dehydropyrrolizidine, include vegetables, grain-derived products, eggs, honey, offal, and milk, due to contamination of the grains by seeds and/or plant fragments from PA-containing weeds growing in the crops used for animal feeding or human consumption (Koleva et al 2012). Grazing animals will generally avoid PA-containing plants; however, in unfavorable conditions, such as overgrazed pastures and favored toxic weed development caused by drought, a behavior of PA-containing weed consumption can be observed (Shimshoni et al 2015). A screening of 350 plant-derived PAs showed that approximately half of them were hepatotoxic and several were carcinogenic (Cushnie et al 2014).…”

“…A screening of 350 plant-derived PAs showed that approximately half of them were hepatotoxic and several were carcinogenic (Cushnie et al 2014). In addition to PAs, iridoid glycoside (IG) presence also confers plant resistance, and a combined defense is often common and most effective for plants to increase protection (Shimshoni et al 2015).…”