Pyrrolizidine Alkaloids
   

1. Name of the Organism:	Pyrrolizidine Alkaloids
2. Nature of Acute Disease:	Pyrrolizidine Alkaloids Poisoning Pyrrolizidine alkaloid intoxication is caused by consumption of plant material containing these alkaloids. The plants may be consumed as food, for medicinal purposes, or as contaminants of other agricultural crops. Cereal crops and forage crops are sometimes contaminated with pyrrolizidine-producing weeds, and the alkaloids find their way into flour and other foods, including milk from cows feeding on these plants. Many plants from the Boraginaceae, Compositae, and Leguminosae families contain well over 100 hepatotoxic pyrrolizidine alkaloids.
3. Nature of Disease:	Most cases of pyrrolizidine alkaloid toxicity result in moderate to severe liver damage. Gastrointestinal symptoms are usually the first sign of intoxication, and consist predominantly of abdominal pain with vomiting and the development of ascites. Death may ensue from 2 weeks to more than 2 years after poisoning, but patients may recover almost completely if the alkaloid intake is discontinued and the liver damage has not been too severe.
4. Diagnosis of Human Illness:	Evidence of toxicity may not become apparent until sometime after the alkaloid is ingested. The acute illness has been compared to the Budd-Chiari syndrome (thrombosis of hepatic veins, leading to liver enlargement, portal hypertension, and ascites). Early clinical signs include nausea and acute upper gastric pain, acute abdominal distension with prominent dilated veins on the abdominal wall, fever, and biochemical evidence of liver disfunction. Fever and jaundice may be present. In some cases the lungs are affected; pulmonary edema and pleural effusions have been observed. Lung damage may be prominent and has been fatal. Chronic illness from ingestion of small amounts of the alkaloids over a long period proceeds through fibrosis of the liver to cirrhosis, which is indistinguishable from cirrhosis of other etiology.
5. Associated Foods:	The plants most frequently implicated in pyrrolizidine poisoning are members of the Borginaceae, Compositae, and Leguminosae families. Consumption of the alkaloid-containing plants as food, contaminants of food, or as medicinals has occurred.
6. Relative Frequency of Disease:	Reports of acute poisoning in the United States among humans are relatively rare. Most result from the use of medicinal preparations as home remedies. However, intoxications of range animals sometimes occur in areas under drought stress, where plants containing alkaloids are common. Milk from dairy animals can become contaminated with the alkaloids, and alkaloids have been found in the honey collected by bees foraging on toxic plants. Mass human poisonings have occurred in other countries when cereal crops used to prepare food were contaminated with seeds containing pyrrolizidine alkaloid.
7. Course of Disease and Complications:	No information currently available.
8. Target Populations:	All humans are believed to be susceptible to the hepatotoxic pyrrolizidine alkaloids. Home remedies and consumption of herbal teas in large quantities can be a risk factor and are the most likely causes of alkaloid poisonings in the United States.
9. Food Analysis:	The pyrrolizidine alkaloids can be isolated from the suspect commodity by any of several standard alkaloid extraction procedures. The toxins are identified by thin layer chromatography. The pyrrolizidine ring is first oxidized to a pyrrole followed by spraying with Ehrlich reagent, which gives a characteristic purple spot. Gas-liquid chromatographic and mass spectral methods also are available for identifying the alkaloids.
10. Selected Outbreaks:	There have been relatively few reports of human poisonings in the United States. Worldwide, however, a number of cases have been documented. Most of the intoxications in the USA involved the consumption of herbal preparations either as a tea or as a medicine. The first patient diagnosed in the USA was a female who had used a medicinal tea for 6 months while in Ecuador. She developed typical hepatic veno-occlusive disease, with voluminous ascites, centrilobular congestion of the liver, and increased portal vein pressure. Interestingly, the patient completely recovered within one year after ceasing to consume the tea. Another herbal tea poisoning occurred when Senecio longilobus was mistaken for a harmless plant (called "gordolobo yerba" by Mexican Americans) and used to make herbal cough medicine. Two infants were given this medication for several days. The 2-month-old boy was ill for 2 weeks before being admitted to the hospital and died 6 days later. His condition was first diagnosed as Reye's syndrome, but was changed when jaundice, ascites, and liver necrosis were observed. The second child, a 6-month-old female, had acute hepatocellular disease, ascites, portal hypertension, and a right pleural effusion. The patient improved with treatment; however, after 6 months, a liver biopsy revealed extensive hepatic fibrosis, progressing to cirrhosis over 6 months. Another case of hepatic veno-occlusive disease was described in a 47-year-old nonalcoholic woman who had consumed large quantities of comfrey (Symphytum species) tea and pills for more than one year. Liver damage was still present 20 months after the comfrey consumption ceased.
Morbidity and Mortality Weekly Reports	For more information on recent outbreaks see the CDC.
11. Education and Background Resources:	Literature references can be found at the links below.
Loci index for genome Senecio spp.	Available from the GenBank Taxonomy database, which contains the names of all organisms that are represented in the genetic databases with at least one nucleotide or protein sequence.
12. Molecular Structural Data:	These structures were created by Fred Fry, Ph.D, CFSAN.
	Pyrrolizidine Alkaloids of Symphytum spp.
	Pyrrolizidine Alkaloids of Senecio longilobus Benth.

CDC/MMWR

The CDC/MMWR link will provide a list of Morbidity and Mortality Weekly Reports at CDC relating to this organism or toxin. The date shown is the date the item was posted on the Web, not the date of the MMWR. The summary statement shown are the initial words of the overall document. The specific article of interest may be just one article or item within the overall report.

NIH/PubMed

The NIH/PubMed button at the top of the page will provide a list of research abstracts contained in the National Library of Medicine's MEDLINE database for this organism or toxin.

AGRICOLA

The AGRICOLA button will provide a list of research abstracts contained in the National Agricultural Library database for this organism or toxin.

mow@cfsan.fda.gov
January 1992 with periodic updates

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