Pyrrolizidine alkaloids. In: Hovda, L.R., Benson, D., Poppenga, R.H., editors. Blackwell's Five-Minute Veterinary Consult Clinical Companion: Equine Toxicology

Authors: Stegelmeier, Bryan

Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 1/5/2021
Publication Date: 1/20/2022
Citation: Stegelmeier, B.L. 2022. Pyrrolizidine alkaloids. In: Hovda, L.R., Benson, D., Poppenga, R.H., editors. Blackwell's Five-Minute Veterinary Consult Clinical Companion: Equine Toxicology. 1st Edition. Hoboken, NJ: John Wiley & Sons, Inc. p. 336-343.

Interpretive Summary: Pyrrolizidine alkaloid (PA) containing plants are estimated to compose over 3% of the worlds flowering plants. Problem plants are invasive and expansive and as result they commonly contaminate feeds and food. Of the hundreds of PAs, only dehydro-pyrrolizidine alkaloids (DHPA) are toxic and only after they are bioactivated. These reactive metabolites covalently bind and damage cellular proteins, nucleic acids and other compounds. This damages cell structure and function producing cellular degeneration, necrosis and ultimately liver failure. Poisoned animals develop jaundice, hyperbilirubinemia, and increased biochemical enzymatic activities with related changes of hepatic damage, hepatic encephalopathy, and photosensitization. Microscopic changes include hepatic degeneration and necrosis, fibrosis, biliary hyperplasia and under some conditions hepatocellular megalocytosis. High doses can be fatal within days of exposure. Lower doses generally have more prolonged exposures and it might take several weeks before animals develop liver failure and die. Even lower doses produce transient clinical disease followed by recovery. DHPA specific indicators of poisoning include recent enhancements of extraction, detection and quantification of DHPA adducts or pyrroles using LC/MS. Marked variation in species, sex and age susceptibility complicates interpreting pyrrole concentrations. A definitive diagnosis requires integration of field studies to identifying exposure and consumption, pathologic studies documenting gross and microscopic lesions and chemical identification of pyrroles. As poisoning, even sublethal exposures, may be progressive and there are no effective treatments or antidotes. Avoiding exposure and ingestion is recommended.

Technical Abstract: Pyrrolizidine alkaloid (PA) containing plants are estimated to compose over 3% of the worlds flowering plants. Problem plants are invasive and expansive and as result they commonly contaminate feeds and food. Of the hundreds of PAs, only dehydro-pyrrolizidine alkaloids (DHPA) are toxic and only after they are bioactivated. These reactive metabolites covalently bind and damage cellular proteins, nucleic acids and other compounds. This damages cell structure and function producing cellular degeneration, necrosis and ultimately liver failure. Poisoned animals develop jaundice, hyperbilirubinemia, and increased biochemical enzymatic activities with related changes of hepatic damage, hepatic encephalopathy, and photosensitization. Microscopic changes include hepatic degeneration and necrosis, fibrosis, biliary hyperplasia and under some conditions hepatocellular megalocytosis. High doses can be fatal within days of exposure. Lower doses generally have more prolonged exposures and it might take several weeks before animals develop liver failure and die. Even lower doses produce transient clinical disease followed by recovery. DHPA specific indicators of poisoning include recent enhancements of extraction, detection and quantification of DHPA adducts or pyrroles using LC/MS. Marked variation in species, sex and age susceptibility complicates interpreting pyrrole concentrations. A definitive diagnosis requires integration of field studies to identifying exposure and consumption, pathologic studies documenting gross and microscopic lesions and chemical identification of pyrroles. As poisoning, even sublethal exposures, may be progressive and there are no effective treatments or antidotes. Avoiding exposure and ingestion is recommended.