Slaframine
Encyclopedia
Slaframine is a kind of piperidine
or indolizidine alkaloidal mycotoxin
that generally causes salivation (slobbers) in most of the animals. It is usually produced by the fungus Rhizoctonia leguminicola
. It is a common fungal pathogen of red clover that causes black patch disease in the plant (Figure 1). Slaframine has the molecular formula C10H18N2O2. The different environmental condition promotes the growth of the Rhizoctonia leguminicola
fungus. For example, wet and humid weather are the favorable environmental condition for the growth of the fungus and production of slaframine. Legume hays contaminated with slaframine causes slobber syndrome and the various animals are sensitive to its effects.
was reported which was mainly associated with a pasture disease called black patch. This was so called because it derives its name from the appearance of affected areas in the field. Most of these cases were associated with the feeding of second-cutting red clover hay.Another serious outbreak of slobbers occurred in a herd of horses in the fall of 1979 near High Point, North Carolina. This was caused by a shipment of high-quality second-cutting red clover-orchard grass hay from a usual supplier in West Virginia. In 2010, the slaframine toxin, or "slobber toxin" was also observed in Central Kentucky because of the wet spring weather and abundant clover growth.
oxidase to the ketoimine metabolite
consisting of quaternary nitrogen
separated from an acetate
ester
by two carbon
atoms (Figure 2).
It is apparent to reveal that the more direct access to hepatic tissues provided by the route of administration, the shorter the time interval to the onset of salivation.
. The other clinical signs associated with the "slobbers syndrome" include salivation, lacrimation, feed refusal, bloating
, stiff joints, diarrhea
, and weight loss.
The clinical signs of slaframine toxicity are similar in all species. When animals are feed with slaframine contaminated forage
then they salivate profusely. The experiment shows that a single dose
of slaframine produces salivation for 6-10 hours. However, clinically affected animals can slobber for several days because they are fed with continued slaframine contaminated forages. Various other animals like sheep, swine, and guinea pigs were also found to suffer from Cyanosis
and open-mouth breathing under experimental conditions in sheep, swine, and guinea pigs. Pigs were also observed to vomit, became dyspneic, and collapse with stiffened pelvic limbs.
in the hay. Although chemical analysis for slaframine is not usually necessary, chromatographic methods for detecting the toxin in hay, plasma
, or milk have been described. Slowly, the slobber symptoms recover when the contaminated hay is removed, however clinical signs may persist for 1-2 days following removal of the toxic forage. In severe cases, atropine
may be of benefit that helps in reversing the parasympathomimetic effects of slaframine, however it is unlikely to be completely resolving clinical signs.
Piperidine
Piperidine is an organic compound with the molecular formula 5NH. This heterocyclic amine consists of a six-membered ring containing five methylene units and one nitrogen atom...
or indolizidine alkaloidal mycotoxin
Mycotoxin
A mycotoxin is a toxic secondary metabolite produced by organisms of the fungus kingdom, commonly known as molds. The term ‘mycotoxin’ is usually reserved for the toxic chemical products produced by fungi that readily colonize crops...
that generally causes salivation (slobbers) in most of the animals. It is usually produced by the fungus Rhizoctonia leguminicola
Rhizoctonia leguminicola
Rhizoctonia leguminicola is a fungus that is a plant pathogen that most often attaches itself to the Trifolium pratense or red clover. It is also called Black Patch Disease. The infection is first seen as small black patches on the leaves of red clover and spreads to cover the entire plant,...
. It is a common fungal pathogen of red clover that causes black patch disease in the plant (Figure 1). Slaframine has the molecular formula C10H18N2O2. The different environmental condition promotes the growth of the Rhizoctonia leguminicola
Rhizoctonia leguminicola
Rhizoctonia leguminicola is a fungus that is a plant pathogen that most often attaches itself to the Trifolium pratense or red clover. It is also called Black Patch Disease. The infection is first seen as small black patches on the leaves of red clover and spreads to cover the entire plant,...
fungus. For example, wet and humid weather are the favorable environmental condition for the growth of the fungus and production of slaframine. Legume hays contaminated with slaframine causes slobber syndrome and the various animals are sensitive to its effects.
History
In the late 1940s and 1950s in Midwestern United States, various agricultural experiment stations revealed the outbreaks of salivation in the cattle. In 1956, the first case of fungal contamination of red clover with Rhizoctonia leguminicolaRhizoctonia leguminicola
Rhizoctonia leguminicola is a fungus that is a plant pathogen that most often attaches itself to the Trifolium pratense or red clover. It is also called Black Patch Disease. The infection is first seen as small black patches on the leaves of red clover and spreads to cover the entire plant,...
was reported which was mainly associated with a pasture disease called black patch. This was so called because it derives its name from the appearance of affected areas in the field. Most of these cases were associated with the feeding of second-cutting red clover hay.Another serious outbreak of slobbers occurred in a herd of horses in the fall of 1979 near High Point, North Carolina. This was caused by a shipment of high-quality second-cutting red clover-orchard grass hay from a usual supplier in West Virginia. In 2010, the slaframine toxin, or "slobber toxin" was also observed in Central Kentucky because of the wet spring weather and abundant clover growth.
Metabolism
Liver is the major site of slaframine metabolism where it has been suggested that slaframine is metabolized in the liver by a microsomal flavoproteinFlavoprotein
Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin: the flavin adenine dinucleotide or flavin mononucleotide ....
oxidase to the ketoimine metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
consisting of quaternary nitrogen
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
separated from an acetate
Acetate
An acetate is a derivative of acetic acid. This term includes salts and esters, as well as the anion found in solution. Most of the approximately 5 billion kilograms of acetic acid produced annually in industry are used in the production of acetates, which usually take the form of polymers. In...
ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
by two carbon
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
atoms (Figure 2).
It is apparent to reveal that the more direct access to hepatic tissues provided by the route of administration, the shorter the time interval to the onset of salivation.
Toxicity
In horses, excessive salivation is usually the first sign of slaframine exposure (Figure 3). Signs typically develop within hours of exposure. The Slaframine poisoning or slobbers likely occur in a cooler and wetter spring or fall because these seasons are ideal for the growth of the fungus Rhizoctonia leguminicolaRhizoctonia leguminicola
Rhizoctonia leguminicola is a fungus that is a plant pathogen that most often attaches itself to the Trifolium pratense or red clover. It is also called Black Patch Disease. The infection is first seen as small black patches on the leaves of red clover and spreads to cover the entire plant,...
. The other clinical signs associated with the "slobbers syndrome" include salivation, lacrimation, feed refusal, bloating
Bloating
Bloating is any abnormal general swelling, or increase in diameter of the abdominal area. As a symptom, the patient feels a full and tight abdomen, which may cause abdominal pain sometimes accompanied by increased borborygmus or more seriously the total lack of borborygmus.-Symptoms:The most common...
, stiff joints, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, and weight loss.
The clinical signs of slaframine toxicity are similar in all species. When animals are feed with slaframine contaminated forage
Forage
Forage is plant material eaten by grazing livestock.Historically the term forage has meant only plants eaten by the animals directly as pasture, crop residue, or immature cereal crops, but it is also used more loosely to include similar plants cut for fodder and carried to the animals, especially...
then they salivate profusely. The experiment shows that a single dose
Dose
Dose means quantity in the following fields:In nutrition, medicine, and toxicology:* Dose , the quantity of something that may be eaten by or administered to an organism, or that an organism may be exposed to...
of slaframine produces salivation for 6-10 hours. However, clinically affected animals can slobber for several days because they are fed with continued slaframine contaminated forages. Various other animals like sheep, swine, and guinea pigs were also found to suffer from Cyanosis
Cyanosis
Cyanosis is the appearance of a blue or purple coloration of the skin or mucous membranes due to the tissues near the skin surface being low on oxygen. The onset of cyanosis is 2.5 g/dL of deoxyhemoglobin. The bluish color is more readily apparent in those with high hemoglobin counts than it is...
and open-mouth breathing under experimental conditions in sheep, swine, and guinea pigs. Pigs were also observed to vomit, became dyspneic, and collapse with stiffened pelvic limbs.
Diagnosis and Treatment
Generally, diagnosis of slaframine toxicity is done by observation of clinical signs (salivation) in animals consuming legume forage, particularly red clover hay. Further tests such as isolating in cultures can be done to identify the fungus Rhizoctonia leguminicolaRhizoctonia leguminicola
Rhizoctonia leguminicola is a fungus that is a plant pathogen that most often attaches itself to the Trifolium pratense or red clover. It is also called Black Patch Disease. The infection is first seen as small black patches on the leaves of red clover and spreads to cover the entire plant,...
in the hay. Although chemical analysis for slaframine is not usually necessary, chromatographic methods for detecting the toxin in hay, plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
, or milk have been described. Slowly, the slobber symptoms recover when the contaminated hay is removed, however clinical signs may persist for 1-2 days following removal of the toxic forage. In severe cases, atropine
Atropine
Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...
may be of benefit that helps in reversing the parasympathomimetic effects of slaframine, however it is unlikely to be completely resolving clinical signs.