Slaframine is an

indolizidine Indolizidine is a heterocyclic chemical compound that forms the central core of the indolizidine alkaloids such as swainsonine and castanospermine. See also * Indole * Indolizine * Tryptophan * Tryptamine Tryptamine is an indolamine metaboli ...

alkaloid Alkaloids are a class of basic BASIC (Beginners' All-purpose Symbolic Instruction Code) is a family of general-purpose, high-level programming languages designed for ease of use. The original version was created by John G. Kemeny and Th ...

mycotoxin A mycotoxin (from the Greek μύκης , "fungus" and τοξίνη , "toxin") is a toxic secondary metabolite produced by organisms of kingdom Fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' ...

that generally causes salivation (slobbers) in most animals. It is usually produced by the fungus ''

Rhizoctonia leguminicola ''Slafractonia leguminicola'' (formerly ''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 fi ...

''. It is a common fungal pathogen of red clover (''

Trifolium pratense ''Trifolium pratense'', the red clover, is a herbaceous species of flowering plant in the bean family Fabaceae, native to Europe, Western Asia, and northwest Africa, but planted and naturalized in many other regions. Description Red clov ...

'') that causes black patch disease in the plant. Slaframine has the molecular formula C₁₀H₁₈N₂O₂.Smith G. W., (2007). Slaframine. In R.C.Gupta (Eds.), ''Veterinary Toxicology: Basic & Clinical Principles'', Chapter 81, pp. 1011-1013 The different environmental condition promotes the growth of the

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.Gaskill C., (2010). Slaframine Toxication. ''Bluegrass Equine Digest''. Retrieved from http://www.ca.uky.edu/gluck/images/BED/BED-July10.pdf on April 12, 2011

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

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.Hagler, W.M. & Behlow, R.F. (1981
Salivary Syndrome in Horses: Identification of Slaframine in Red Clover Hay
"Applied and Environmental Microbiology", 42 (6):1067-1073 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

flavoprotein Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin. Flavoproteins are involved in a wide array of biological processes, including removal of radicals contributing to oxidative stress, photosynthesis, and DNA repair. T ...

oxidase to the ketoimine

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

consisting of quaternary

nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at seve ...

separated from an

acetate An acetate is a salt formed by the combination of acetic acid with a base (e.g. alkaline, earthy, metallic, nonmetallic or radical base). "Acetate" also describes the conjugate base or ion (specifically, the negatively charged ion called ...

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...

by two

carbon Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon makes ...

atoms Every atom is composed of a nucleus and one or more electrons bound to the nucleus. The nucleus is made of one or more protons and a number of neutrons. Only the most common variety of hydrogen has no neutrons. Every solid, liquid, gas ...

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.Cheeke P.R. (1989).Slaframine: Occurrence, Chemistry, and Physiological Activity. In "Toxicants of Plant Origin", Chapter 10, Volume 1, CRC Press. Retrieved from https://books.google.com/books?%20hl=en&lr=&id=79i9mfl2PO4C&oi=fnd&pg=PA257&dq=slaframine&ots=vEkgaadrhh&sig=yhotBnXTPxzkiBXp63C3aBPpAwY#v=onepage&q=slaframine&f=false on April 8th, 2011

Toxicity

In horses, excessive salivation is usually the first sign of slaframine exposure. 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

. The other clinical signs associated with the "slobbers syndrome" include salivation, lacrimation, feed refusal,

bloating Abdominal bloating (or simply bloating) is a short-term disease that affects the gastrointestinal tract. Bloating is generally characterized by an excess buildup of gas, air or fluids in the stomach. A person may have feelings of tightness, pressu ...

, stiff joints,

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin ...

, and weight loss. The clinical signs of slaframine toxicity are similar in all species. When animals are fed with slaframine contaminated

forage Forage is a plant material (mainly plant leaves and stems) 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 us ...

then they salivate profusely. The experiment shows that a single

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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 is the change of body tissue color to a bluish-purple hue as a result of having decreased amounts of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Body tissues that show cyanosis are usually in locations ...

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

in the hay. Although chemical analysis for slaframine is not usually necessary, chromatographic methods for detecting the toxin in hay,

plasma Plasma or plasm may refer to: Science * Plasma (physics), one of the four fundamental states of matter * Plasma (mineral), a green translucent silica mineral * Quark–gluon plasma, a state of matter in quantum chromodynamics Biology * Blood plas ...

, 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 is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically giv ...

may be of benefit that helps in reversing the parasympathomimetic effects of slaframine, however it is unlikely to be completely resolving clinical signs.

References

{{Reflist Alkaloids Mycotoxins Acetate esters