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Coumarin Glycosides

This section will discuss toxicants that are derived from coumarin compounds in plants. For example, the glucoside melilotoside found in sweet clover (Melilotus alba and M.officinalis) is an ether of glucose bonded with an ester bond to coumarin. It yields the toxicant dicoumarol when exposed to specific molds. Furocoumarins are toxic compounds that consist of a coumarin nucleus bonded to a furan ring. Several plants contain the psoralens that are generally the precursors of furocoumarins.

[Dicoumarol] [Furocoumarins] [Return to list of toxicants]

Dicoumarol

Formation of Coumarin and Dicoumarol

Sweet clover ( Melilotus alba and M. officinalis is grown as a green manure and hay crop in the northern U.S. and in Canada. Its coumarin content gives it a distinctive sweet odor similar to vanilla. Its use as hay was widespread in the 1920s. A series of wet summers led to an epidemic of "bleeding disease" in cattle. Use of the forage is less common now and low- melilotoside varieties are available. Sweet vernal grass ( Anthoxanthum odoratum is a coumarin-containing forage in England that also causes "bleeding disease". Hay with >10 ppm dicoumarol should be viewed with caution.

Similarity among Dicoumarol, Vitamin K, and Warfarin

How Poisoning Occurs:

Plant enzymes in sweet clover partition the aglycone coumarin from melilotoside. When sweet clover is put up as hay it is easy for it to be contaminated with molds because of its succulent stems. This is particularly likely when conditions are wet at cutting or curing or when foliage is lush. Molds such as Penicillium nigricans , P.jensi , and the Aspergillus metabolize the coumarin into dicoumarol. Dicoumarol is similar in structure to

Process of Blood Clotting.

vitamin K. When consumed by livestock it inhibits vitamin K production. Vitamin K is necessary in the body to activate prothrombin. When tissue is damaged, thromboplastin is released and converts prothronin to thrombin. Thrombin alters the solubility of fibrinogen in blood and causes it to clot and seal the tissue damage. Dicoumarol prevents this process. Warfarin is a synthetic toxicant derived from coumarol. It is used in rat, gopher, and ground squirrel poisons and also acts as a vitamin K inhibitor to block the blood clotting process and provoke hemorrhaging. It is toxic to livestock that may accidently consume it in its pelleted form and to dogs that consume poisoned squirrels,etc.

Psoralen: most furocoumarins have a furan ring fused with a coumarin nucleus and are derivatives of psoralen.

Symptoms of Poisoning:

Bleeding disease "only in cattle?"

  1. mild cases - extended blood-clotting time that can lead to hemorrhaging when livestock are castrated or dehorned.
  2. severe cases - internal and/or external hemorrhaging cause pale mucous membranes, subcutaneous swellings of pooled blood, weakness, and death.
  3. treatment - injections of vitamin K, whole blood transfusion.

Furocoumarins

Bishop's weed (Ammi majus), spring parsley(Cymopterus watsonii), and dutchman's breeches (Thamnosma texana and T. montana) are weeds found in different rangeland regions of the U.S. Livestock consume them as forage or as seed contamination in grain. They contain several psoralens including xanthotoxin and bergapten that break down readily to form furocoumarins. Furocoumarins are also produced by some plants, for example, celery and parsnips, in response to fungal infestation.

How Poisoning Occurs:

Furocoumarins are primary photodynamic agents. They absorb long-wave ultra-violet radiation upon exposure of the skin of the affected animal to sunlight and become photoactive. They then cause cell damage by inhibiting DNA synthesis by binding pyrimidine bases and nucleic acids.

Symptoms of Poisoning:

  1. severe blistering and peeling particularly of light-skined parts of the animal
  2. clouding of the cornea and eye lesions -->severe cases - blindness
  3. blistering and erythema of the udder of lactating females, e.g. ewes and cows, -->severe cases - starvation of their offspring when dams refuse to nurse
  4. "celery dermatitis" - blistering of arms of farm workers handling celery when the celery is diseased with pink rot (Sclerotinia sclerotiorum) and produces xanthotoxin and trisoralen.