Abrin
Abrin-a | |||||||
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UniProt P11140 | | ||||||
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KEGG | |
RTECS number
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UNII | |
UN number | 3462 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Abrin is an extremely toxic
Abrin is a
Occurrence
Abrin is formed in nature by only the rosary pea. The brightly coloured seeds of this plant contain about 0.08% of abrin. The toxin is found within the seeds, and its release is prevented by the seed coat. If the seed coat is injured or destroyed (by chewing, for example) the toxin may be released.
Physical properties
Abrin is a water-soluble
Biochemistry
Chemically, abrin is a mixture of four isotoxins, these being abrin-a (P11140), -b (Q06077), -c (P28590), and -d (Q06076). Occasionally, the non-toxic hemagglutinin of Abrus precatorius (Q9M6E9; AAG) is also included as the fifth protein under the collective name 'abrin'.
Abrin-a is the most potent of the four isotoxins, encoded for by an intron-free
In terms of structure, abrin-a is related to the lectin,
Use
Abrin is not known to have been weaponised.[5] However, due to its high toxicity and the possibility of being processed into an aerosol, the use of abrin as a biological weapon is possible in principle.[7] Despite this, the rosary pea yields only small quantities of abrin, which reduces the risk.
The rosary pea is common to tropical regions, and is occasionally employed as an herbal remedy for certain conditions.
Abrin has been shown to act as an immunoadjuvant in the treatment of cancer in mice.[9]
Toxicology
Symptoms of abrin poisoning include
Toxicity
Although there is no consensus on the level of lethal dose in humans after oral intake, it is assumed that the intake of 0.1 to 1 microgram per kilogram of body weight, or the consumption of a single seed of the rosary pea, may be fatal, but this information is insufficiently documented. however, there is no evidence of toxicity after skin contact.
Abrin is significantly more toxic following intravenous administration. The LD50 values obtained vary between 0.03 and 0.06 μg/kg in rabbits and between 1.25 and 1.3 μg/kg in dogs, depending on the species.[11] In clinical studies involving cancer patients, up to 0.3 μg/kg of intravenous abrin immunotoxin was tolerated without the development of serious symptoms of toxicity.
The toxicity of abrin is increased if it is inhaled. In rats, the LD50 for this route of administration is 3.3 μg/kg.[12]
Toxicodynamics
Abrin resembles ricin, in that it also is a type 2 ribosome-inactivating protein (RIP-II) with a similar mode of action, but the effect of abrin is more potent than that of ricin.[13] The toxic effect of abrin is due to an intracellular, multi-step process. Abrin binds to and penetrates the cells of the body, inhibiting cell protein synthesis after being transported to the endoplasmic reticulum (ER). By attaching its non-specifically binding B chain, which acts as a haptomer, to the carbohydrate chain of a glycoprotein on the cell surface, the abrin molecule anchors itself to the cell and is subsequently engulfed. However, both specific and nonspecific binding result in the uptake of abrin via endocytosis, as well as the activation of the A chain, caused by the cleavage of the B chain. The activated A chain of abrin, the effectomer, then enters the inner parts of the cell, where it cleaves an adenine (A4324) nucleobase from the 28S rRNA of the large ribosomal subunit of a ribosome on or near the ER, inhibiting the regular process of cellular protein synthesis. Without these proteins, cells cannot survive. This is harmful to the human body and can be fatal in small exposures. Additionally, abrin also may bind to cells specifically bearing the mannose receptor on their surface; since this receptor is found in a particularly high density on cells of the reticulohistiocytic system, that system in particular is affected by the toxicity of abrin.[7]
Toxicokinetics
Information dealing with the toxicokinetics of abrin is limited and debated. Due to its biochemical properties and its similarity to ricin, it is believed that abrin is at least partially degraded in the gastrointestinal tract.[14] The size of the molecule also restricts absorption through the gastrointestinal tract. Nevertheless, the numerous deaths caused from consuming rosary pea seeds confirm that enough of the toxin can be absorbed into the systemic circulation via the gastrointestinal tract to cause death.[7]
Murine studies show that there is an accumulation of abrin after
Signs and symptoms of abrin exposure
The major symptoms of abrin poisoning depend on the route of exposure and the dose received, though many organs may be affected in severe cases. In general, symptoms can appear anywhere between several hours to several days after exposure. Initial symptoms of abrin poisoning by inhalation may occur within 8 hours of exposure but a more typical time course is 18–24 hours; they can prove fatal within 36–72 hours. Following ingestion of abrin, initial symptoms usually occur rapidly, but can take up to five days to appear.[6]
The later signs and symptoms of exposure are caused by abrin's cytotoxic effects, killing cells in the kidney, liver, adrenal glands, and central nervous system.[6]
Inhalation
Within a few hours of inhaling abrin, common symptoms include fever, cough, airway irritation,
Ingestion
Swallowing any amount of abrin can lead to a slow-burn process of severe symptoms. Early symptoms include
Absorption
Abrin can be absorbed through broken skin or absorbed through the skin if dissolved in certain solvents. It can also be injected in small pellets and absorbed through contact with the eyes. Abrin in the powder or mist form can cause redness and pain in the eyes (i.e.
Treatment
Because no
See also
- European mistletoe
- Ricin
References
- PMID 6806598.
- PMID 19239732.
- S2CID 20411255.
- PMID 28790381.
- ^ a b c d "Facts About Abrin". CDC.gov. Centers for Disease Control and Prevention. Archived from the original on 2006-09-28.
- ^ a b c d e f g h i j k "The Emergency Response Safety and Health Database: Biotoxin: ABRIN – NIOSH". cdc.gov. Centers for Disease Control and Prevention. Retrieved 2015-12-30.
- ^ S2CID 20411255.
- ^ "Indian Herbs – Rosary Pea". iloveindia.com.
- PMID 7083176.
- PMID 19239732.
- PMID 529341.
- .
- PMID 8023336.
- PMID 5270832.
- PMID 974006.
External links
- Abrin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- "Abrin: Biotoxin". The Emergency Response Safety and Health Database. National Institute for Occupational Safety and Health. 2018-09-27.
- "The Crystal Structure of Abrin-A". Proteopedia.