Ragwort Poisoning how does it work

By: Esther Hegt and Dr. Pieter B. Pelser ( University of Canterbury- Biological Sciences, Christchurch, New Zealand)

Common ragwort (Jacobaea vulgaris) and all other Ragworts and Groundsels growing in the Netherlands (Family Asteraceae; Tribe Senecioneae) contain compounds that are poisonous to most vertebrates and insects (1-3). There are 6000 plantspecies who produce PAs (3 % of all flowering plants7, 23, 25).. These secondary metabolites are called pyrrolizidine alkaloids (PAs). Ragwort poisoning can take place when animals eat fresh or dry plants. Because fresh plants have a repellent smell and taste, these are usually avoided (4-12) . In dried plants, however, the smell and taste is much less noticeable and animals can therefore not always recognize Ragworts and Groundsels as being toxic (6, 7), especially when these plants end up in hay (7, 13) .

How to recognize Ragwort poisoning

The symptoms of pyrrolizidine alkaloid poisoning are not very specific and include weight loss, lack of appetite and energy, dull coat, crusts, especially on the coronary band (horses), photosensitation, jaundice, and neurological signs, such as staggering, walking in circles, inattentiveness, restlessness, and panicking behavior (7, 14-19). These symptoms often merely indicate liver failure, which can have many causes, such as birth defects, bacterial and viral infections, and parasites, but can also be caused by toxins other than PAs (20, 21) .
Only if an animal eats relatively large amounts of PA containing plants it will show symptoms of Ragwort poisoning. Exact amounts are not known, but are estimated to be somewhere between 1 and 10% of an animal’s body weight. (14, 15, 22) For a 500 kg horse, this would come down to eating between 250 and 2500 full grown Common ragwort shoots, which are approximately 20 grams when dried. If this takes place in a relatively short time, it results in acute PA poisoning, but most cases result from eating smaller amounts of Ragwort over an extended period of time: chronic poisoning.
Because PAs are excreted from an animal’s body in roughly 24 to 48 hrs (7, 23-25), PAs can only be found in blood and tissue when samples are taken relatively shortly after an animal has eaten Ragwort (28). A biopsy or post mortem can show more specific liver damage (20, 21) and blood samples can be tested for liver enzymes that may indicate Ragwort poisoning (28). But because owners rarely have such examinations performed on their animals (Gezondheidsdienst Voor Dieren, pers. comm.), these are usually diagnosed to have suffered from Ragwort poisoning when symptoms of liver failure coincide with finding Ragwort plants in hay or on fields where they graze. Consequently, cases of Ragwort poisoning may remain undetected or, alternatively, PA poisoning may be concluded when in fact other factors were responsible for the liver failure observed.

How do PAs damage the liver?

As mentioned earlier, PA poisoning can result from eating a lot of PA containing plants in a short time, but also from regularly eating smaller amounts over a longer time (23-25). Although both types of PA poisoning (acute and chronic) result in liver damage and have the same symptoms, they have a different effect on liver cells.
Acute poisoning results in a substantial amount of necrosis in the liver. Necrosis is the uncontrolled death of cells (7, 23, 25). The liver cells are simply exposed to such a high concentration of the toxic PAs that they die in large numbers, which results in a lot of dead tissue in the liver. The body responds to this by inducing an infection . Consequently, the animal will become seriously ill (23, 25). Not only because a large part of the liver is not functional any more, but also because it is infected. Depending on the scale of the damage, an animal will die or recover (5, 26, 27). During recovery, the dead liver tissue will be broken down and removed by infection cells and connective tissue will be produced to fill the affected areas. This means that a part of a normal functioning liver has been removed. The extent of the loss of liver function depends on the size of this part. If this loss is small, an animal will not show any signs of illness, but when it is substantial the animal will clearly show symptoms of liver failure (16-19).
In contrast to acute PA poisoning, chronic poisoning does not lead to large scale necrosis (23-25). Although liver cells that are heavily damaged will enter necrosis, their number will be relatively small if only small amounts of Ragwort are eaten. Chronic PA poisoning therefore usually does not result in liver infections. Cells that are only lightly damaged will show apoptosis (7, 23, 25). Apoptosis is defined as controlled cell death (as opposed to the uncontrolled cell death of necrosis). These cells release signaling compounds to indicate that they are damaged and therefore may form a risk to healthy cells, because they may enter necrosis or change into tumor cells (research on rats and mice has shown that PA poisoning may induce liver tumors; (23, 25) ). During apoptosis, a cell disintegrates in closed vesicles, which are absorbed by neighboring cells. It is important to notice that apoptosis does not result in infections. As long as there aren’t too many cells that enter the process of apoptosis, the loss of liver function can be compensated by other cells and the liver will therefore stay healthy. So, there will be no symptoms of liver failure and blood samples will not show enzymes that are characteristic of PA poisoning. Lost cells can be replaced by liver cells that can still divide (26, 27). Furthermore, if liver cells were only mildly damaged, they can even recover. In summary, below a certain threshold, PA poisoning will not result in irreparable liver damage. An animal can eat PA containing plants, but will only become ill when it eats too much of these plants. In these cases the liver compensates for the damaged cells and an animal will not show any symptoms, not even in blood samples. If, however, larger amounts of Ragwort are eaten, this is first noticeable in blood samples, which will show certain liver enzymes that are indicative for PA poisoning. This is followed by symptoms of liver failure. It is currently not known how high these levels are, but this will vary for each species and individual (16-19). In very severe cases of chronic Ragwort poisoning, blood samples will not show the characteristic liver enzyme pattern, simply because there aren’t enough liver cells any more that will produce these enzymes.

Read more about Pyrrolizidine alkaloid metabolism

In collaboration with Merijn Roos (veterinarian at the Faculteit Diergeneeskunde in Utrecht).

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