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Overview of Pyrrolizidine Alkaloidosis

(Seneciosis, Senecio poisoning, Ragwort toxicity)

By Rob Bildfell, DVM, MSc, DACVP, Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University

Typically, pyrrolizidine alkaloidosis is a chronic poisoning that results in hepatic failure. It is caused by many toxic plants, most commonly of the genera Senecio, Crotalaria, Heliotropium, Amsinckia, Echium, Cynoglossum, and Trichodesma. These plants grow mainly in temperate climates, but some (eg, Crotalaria spp) require tropical or subtropical climates. The plants most often implicated include ragwort (S jacobea), groundsel (S riddellii, S longilobus), rattleweed (Crotalaria retusa), and seeds of yellow tarweed (A intermedia).

Cattle, horses, farmed deer, and pigs are most susceptible; sheep and goats require ~20 times more plant material than cattle. Individual susceptibility varies greatly within species; young growing animals are most susceptible.

Etiology and Pathogenesis:

More than 300 toxic factors (alkaloids with a pyrrolizidine base) have been found in plants, with some plants containing a mixture of several different pyrrolizidine alkaloid toxins. S jacobea contains jacobine; retrorsine, seneciphylline, and monocrotaline are other pyrrolizidine alkaloids frequently incriminated in toxicities.

These plants, which under normal conditions are avoided by grazing animals, may be eaten during drought conditions. Some animals may eat these plants preferentially as roughage when they are available on extremely lush pasture. Animals are also poisoned by eating the plant material in hay, silage, or pellets. Seeds from Crotalaria, Amsinckia, and Heliotropium spp, which have been harvested with grain, have caused disease in horses, cattle, pigs, and poultry.

The alkaloids are metabolized in the liver to highly reactive pyrroles, which produce cytotoxic effects on target sites, most commonly the nuclei of hepatocytes. Other target sites may include the epithelial and vascular tissues of the kidneys and lungs. These toxic pyrroles cross-link DNA strands and also unite DNA with nucleoproteins such as actin. These molecular alterations are presumed to create the cytotoxic, antimitotic, and megalocytic effects characteristic of pyrrolizidine alkalosis.

Clinical Findings:

Hepatic pathology with associated clinical signs is the most common manifestation of pyrrolizidine alkalosis in domestic animal species. Acute intoxication is characterized by sudden death from hemorrhagic hepatic necrosis and visceral hemorrhages. This is a rare event, because the poor palatability of these plants makes rapid ingestion of large quantities of the toxins uncommon. More chronic exposure is typical, and the liver reflects the cumulative and progressive effects of repeated ingestion of small doses of toxin. Clinical signs may not be seen for several weeks or months after initial exposure. Consumption of the offending plant may even have ceased months earlier. The ongoing hepatic damage in these instances is suspected to be due to the recycling of toxic pyrroles as they are released from one dying cell and taken up by another. Clinical progression may also be altered by concurrent hepatic pathology; a hemolytic crisis may be precipitated in sheep with excessive hepatic copper stores (see Copper Poisoning).

In horses and cattle, signs include loss of condition, anorexia, dullness, and constipation or diarrhea. Tenesmus and passing of bloodstained feces may be followed by rectal prolapse, especially in cattle. Ascites and icterus may be present, and cattle and sheep sometimes show intermittent photosensitization (see Photosensitization). Some animals become progressively weaker and reluctant to move. Others exhibit signs of hepatic encephalopathy such as head-pressing, yawning, aimless wandering, or even frenzied and aggressive behavior. Pica may be seen. Death may occur suddenly or after prolonged recumbency with hepatic coma and high levels of ammonia in the blood.

Less common clinical signs that have been described with pyrrolizidine toxicoses include inspiratory dyspnea in ponies due to laryngeal and pharyngeal paralysis, dyspnea due to interstitial pneumonia in horses, and renal disease in pigs.


In acute cases, the liver may be enlarged, hemorrhagic, and icteric. In chronic cases, it is atrophied, fibrous, finely nodular, and usually pale with a glistening surface due to fibrous thickening of the capsule. Other livers are markedly icteric. The gallbladder is often edematous and grossly distended with thick, mucoid bile. Edema of the abomasum and segments of the bowel, mesentery, and associated lymph nodes is common, and there may be ascites. In some cases, numerous small hemorrhages are present in the abdominal serous membranes. The lungs of some severely affected horses may be emphysematous and fail to collapse (often due to ingestion of Crotalaria spp).

Characteristic histologic changes occur in the liver. Irreversible enlargement of individual hepatocytes (megalocytosis) is often seen; it is conspicuous in horses and sheep but less pronounced in cattle. In cattle, marked perivenous fibrosis of sublobular veins is usually present, but this is not a consistent finding in horses and sheep. In all species, increases in connective tissue, both within and around the lobules, are marked. Bile duct hyperplasia is variable but may be the most striking microscopic change seen in some livers. Pulmonary changes seen in horses exposed to some Crotalaria spp may include hyperplasia of bronchoalveolar epithelium, congestion, septal fibrosis, and emphysema. Renal tubular lining cells and glomerular epithelial cells also may be individually enlarged in pigs.


Chemical analysis of whole blood for toxic metabolites can confirm recent exposure but depends on the half-life of RBCs to which these pyrroles are bound. An ELISA that recognizes riddelliine and closely related pyrrolizidine alkaloids present in whole blood has also been described but is not widely available. More commonly, a presumptive diagnosis is made based on clinical signs, compatible changes in biochemical parameters, and a history of exposure. When hepatic cirrhosis is extensive, hypoalbuminemia and hyperglobulinemia develop. Serum levels of fibrinogen, bilirubin, γ-glutamyltransferase, and glutamate dehydrogenase may be increased, but it should be recognized that the insidious nature of this disease can result in surprisingly mild serum biochemical changes. Hepatic biopsy is often useful, especially if megalocytic change is seen. Other hepatotoxins, such as copper or aflatoxin, as well as infections such as chronic fascioliasis, must be considered before making the diagnosis. At necropsy the diagnosis can often be made based on gross findings, together with characteristic histologic changes in hepatic, pulmonary, and/or renal tissues. Hepatic assay for pyrrolic metabolites can also be performed.

Treatment and Control:

Further intake of toxic plant material must be prevented. Animals showing signs rarely recover, and lesions present in asymptomatic animals may progress and result in further losses over several months. Because high protein intake may precipitate clinical signs, rations high in carbohydrates are indicated. Supportive treatment for dehydration and photosensitization may be needed.

Preventing further outbreaks by reducing exposure should be stressed.

Sheep are commonly used for grazing control of these plants, but this practice carries risks unless sheep destined for early slaughter are used. Biologic control of plants with predator moths, flea beetles, and seed flies has met with variable success. Senecio and related toxic species in pastures have been controlled satisfactorily by annual herbicide applications, preferably in spring before hay or silage conservation.

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