Slaframine is an bicyclic

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

mycotoxin A mycotoxin (from the Greek μύκης , "fungus" and τοξικός , "poisonous") is a toxic secondary metabolite produced by fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' is usually rese ...

that causes salivation (slobbers) in most animals. It is usually produced by the fungus '' Rhizoctonia leguminicola'' which is a common fungal pathogen of red clover (''

Trifolium pratense ''Trifolium pratense'' (from Latin prātum, meaning meadow), red clover, is a herbaceous species of flowering plant in the bean family, Fabaceae. It is native to the Old World, but planted and naturalised in many other regions. Description ...

'') 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 Wet and humid weather are the favorable environmental condition for the growth of the fungus and production of slaframine. Legume hays contaminated with slaframine cause slobber syndrome and 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 '' Rhizoctonia leguminicola '' was reported which was mainly associated with a pasture disease called black patch, which 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

The liver is the major site of slaframine metabolism. 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. These proteins are involved in a wide array of biological processes, including removal of radicals contributing to oxidative stress, photosynthesis, and DNA repair. ...

oxidase to the active

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, c ...

consisting of a quaternary

nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...

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 acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

by two

carbon Carbon () is a chemical element; it has chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetravalent—meaning that its atoms are able to form up to four covalent bonds due to its valence shell exhibiting 4 ...

atoms Atoms are the basic particles of the chemical elements. An atom consists of a nucleus of protons and generally neutrons, surrounded by an electromagnetically bound swarm of electrons. The chemical elements are distinguished from each other ...

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. Signs typically develop within hours of exposure. Slaframine poisoning or slobbers usually occur in a cooler and wetter spring or fall because these seasons are ideal for the growth of the fungus Rhizoctonia leguminicola. 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 (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

, 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 used m ...

then they salivate profusely. The experiment shows that a single

dose Dose or Dosage may refer to: Music * ''Dose'' (Gov't Mule album), 1998 * ''Dose'' (Latin Playboys album) * ''Dosage'' (album), by the band Collective Soul * "Dose" (song), a 2018 song by Ciara * "Dose", song by Filter from the album '' Short ...

of slaframine produces salivation for 6–10 hours. However, clinically affected animals can salivate for several days because they continue to be fed with slaframine contaminated forages. Various other animals like sheep, swine, and guinea pigs were also found to suffer from

cyanosis Cyanosis is the change of Tissue (biology), tissue color to a bluish-purple hue, as a result of decrease in the amount of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Cyanosis is apparent usually in the Tissue (bi ...

and open-mouth breathing under experimental conditions. 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 leguminicola 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. The slobber symptoms pass slowly 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 give ...

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

References

{{Reflist Alkaloids Mycotoxins Acetate esters Nitrogen heterocycles