Pyrrolizidine alkaloid toxicity in livestock: a paradigm for human poisoning?

Abstract

Livestock poisoning, primarily liver damage, caused by consumption of plants containing 1,2-dehydropyrrolizidine ester alkaloids (dehydroPAs), and the corresponding N-oxides, is a relatively common occurrence worldwide. Because of the economic impact, extensive investigations of such episodes have been performed, particularly in Australia, South Africa the United States and, more recently, South America. Plant species most commonly involved are members of the families Boraginaceae, Asteraceae and Leguminosae. These may be native species that periodically flourish under particular climatic conditions or introduced species that thrive in the absence of natural control factors such as herbivory and competition. Contamination of grain crops with dehydroPA-producing plants has resulted in large-scale incidents of food poisoning in humans, with high morbidity and mortality, especially in Africa and in central and south Asia, with recent episodes in Afghanistan and possibly Ethiopia. Attention has recently focused on the potential for low levels of dehydroPAs to contaminate many food products in developed countries, possibly leading to progressive, chronic diseases that may not include overt hepatotoxicity. This overview examines the potential for better control of exposure and means of monitoring dehydroPA intake by extrapolation of knowledge gained from animal studies to the human situation.

Keywords:

• exposure assessment
• toxicology
• animal study
• metabolism
• chromatographic analysis
• natural toxicants
• alkaloids
• animal feed
• cereals and grain
• dietary supplements
• honey

Acknowledgements

The advice and encouragement of Dr Joerg Stroka in preparing this overview is gratefully acknowledged. The authors also thank Dr Joseph M. Betz, Director, Dietary Supplement Methods and Reference Materials Program, Office of Dietary Supplements, for advice and partial support of this work through the National Institutes of Health Interagency Agreement, No. 60-5428-9-451 ‘Development and Validation of Selected Methodology for the Determination of Pyrrolizidine Alkaloids in Dietary Supplements’. Dr Francis Williams, Combined Security Transition Command, Kabul, Afghanistan, is thanked for personal communications regarding the situation with respect to ‘charmak’ disease in Afghanistan. Dr E. Danielle Rentz and Colleen Martin, and Dr Arunmozhi Balajee and Dr Eszter Deak, Centers for Disease Control and Prevention, Atlanta, Georgia, are gratefully acknowledged for providing samples of millet and teff from Tigray, and for preliminary results on analysis of aflatoxins in Ethiopian grain samples, respectively.