Ricin is a protein extracted from the seeds of the castor bean works ( Ricinus communis ) . Ricin is a lectin and a member of a group of ribosome-inactivating proteins like abrin ( from the seeds of the rosary pea, Abrus precatorius ) , that prevent synthesis of protein in eucaryotic ribosomes. Ricin is one of the most toxic substances and as such was one time known to be a chemical arm ( Agent W ) but is now capable to the Chemical Weapons Convention. However, ricin has been used as a toxicant for condemnable and terrorist intents.
Ricin is an highly toxic toxicant, and therefore can kill even if applied in a little sum. Therefore, the debut of rapid, extremely sensitive chemical and biological/immunological analytical methods capable of observing the toxin at or below ng/ml degree is of critical importance ( see, for illustration, Kalb and Barr, 2009 ; Lubelli et al. , 2006 ; Uzawa et al. , 2008 ) . In instances where Castor beans or petroleum ricin readyings are the perchance unsafe toxicants, ricinine can besides function as a biomarker ( see, for illustration, Mouser et al. , 2007 ) .
The chemical is peculiarly lifelessly because it can be inhaled, ingested, or swallowed and is rapidly broken down in the organic structure and is virtually undetectable. There is presently no counterpoison to ricin, although a prospective vaccinum has been developed that has been successfully tested in mice. Ricin is a powerful protein cytotoxin derived from the beans of the Castor works. Castor beans are ubiquitous worldwide, and the toxin is reasonably easy to pull out ; hence, ricin is widely available. Ricin ‘s significance as a possible BW [ biological warfare ] toxin relates in portion to its broad handiness.
HOW IT IS OBTAINED
Ricin toxin, found in the bean of the Castor works, Ricinis communis, is one of the most toxic and easy produced works toxins. The bush like cosmetic Castor works, Ricinus communis ( Euphorbiaceae ) , originated in Africa and Asia, and has been cultivated and distributed throughout the universe. The one-year production of Castor oil seed exceeds over 1 million metric metric tons ( Food and Agricultural Organization of the United Nations, 2009 ) . Ricin is a by-product of Castor oil production: when Castor beans are crushed, they form a mush from which Castor oil is extracted, and ricin is what remains. The waste mash from this procedure is 3-5 % ricin by weight. The seeds of the works have three chief components: oil, Castor oil, which is the acylglycerol of ricinoleic acid ; a mildly toxic alkaloid ricinine and several isoforms of a extremely toxicant glycoprotein ricin present up to 5 % in the seeds.
Although adaptable to a broad temperature scope, it fails to defy to subfreezing temperatures and withstand best in elevated year-around temperatures. Brazil, Ecuador, Ethiopia, Haiti, India, and Thailand are the states which commercially cultivate most of the seeds. Castor oil is found in many normally used substances such as pigments, varnishes, and lubricating oils, and is besides used as a cathartic. After oil isolation, the staying seed bar may be detoxified by heat intervention and used as an carnal provender addendum. The seed hulls are similar to barnyard manure in their fertiliser value. The toxicity of Castor beans has been known since antediluvian times and more than 750 instances of poisoning in worlds have been described. Although ricin ‘s deadly toxicity is about 1,000-fold less than that of botulinus toxin, ricin may hold significance as a biological arm because of its heat stableness and world-wide handiness, in monolithic measures, as a byproduct of Castor oil production.
B. DESCRIPTION OF THE AGENT
Identity and Physicochemical Properties
Ricin is a 66-kilodalton ( kd ) globular protein that makes up 1 % to 5 % by weight of the bean of the Castor works, Ricinis communis. The CAS Registry Number of ricin is [ 9009-86-3 ] . In a pure province, ricin is a white crystalline pulverization. It is a water-soluble glycoprotein dwelling of two polypeptides, termed A and B ironss, which are linked by a disulfide bond ( ASSB ) . The amino acerb sequence of ricin ( or ricin D as the toxic fraction from the beans is called ) was resolute by Funatsu et Al. ( 1978, 1979 ) .
The A concatenation contains 265 amino acids and has a molecular weight of 32 kDa ; its sugar content is 2.6 % . The isoelectric point of the A concatenation is 7.34. The B concatenation of 260 aminic acids and four internal disulfide bonds has a molecular weight of 34 kDa and its sugar content is 6.4 % . The A concatenation has enzymatic belongingss ( ribosomal RNA N-glycosidase, EC 3.2.2.22 ) responsible for the toxicity of ricin, while the B concatenation is a lectin binding to galactose-containing glycoproteins and glycolipids on the surface of mark cell constituents. The usage of X-ray crystallography surveies was used to work out the 3-dimensional construction of ricin ( reviewed by Lord et al. , 1994 ) . The physicochemical and photochemical belongingss of ricin have late been assessed ( Gaigalas et al. , 2007 ) .
Stability
Because the husk left over from Castor oil processing can be used to feed cowss, a great trade of attempt was dedicated to its detoxification ( Balint, 1974 ; European Food Safety Authority, 2008 ) . High-temperature denaturing ( & A ; gt ; 80 & A ; deg ; C for 1 H ) and chemical methods ( oxidization with K permanganate, H peroxide, I, etc. ) were put frontward to destruct the toxin ( see, for illustration, Barnes et al. , 2009 ) . In the presence of 2-mercaptoethanol, which reduces the disulfide bond fall ining the A and B ironss, the toxicity of ricin is lost ; remotion of 2-mercaptoethanol, nevertheless, allows the reconstitution and reactivation of the toxin. Ricin is degraded by papain but merely easy by trypsin. The destiny of ricin in the organic structure is incompletely understood.
Use
The toxin-rich husk by-product of Castor oil industry has been used to kill mice and moles. Conjugate solutions of ricin and cell-specific antibodies are experimental antineoplastic immunochemotherapeutic agents ( Sandvig and new wave Deurs, 2005 ; Stirpe et al. , 1992 ) . Recently, transgenic rice and maize engineered to bring forth a merger protein consisting the Cry1Ac endotoxin of Bt and the ricin B lectin fractional monetary unit have proved to be insecticidal to insects that are otherwise able to digest Cry toxins ( Mehlo et al. , 2005 ) .
Mode of action
Once it was thought that the toxic action of ricin readyings in mammals is due to its haemagglutinating consequence, but this activity was shown to be associated with the structurally similar, but atoxic agglutinins present in the Castor bean. It is now good established that ricin inhibits protein synthesis in eucaryotic systems by catalytically demobilizing the 60S fractional monetary unit involved in the interlingual rendition procedure. The structural facets of biochemical interaction of ricin and other ribosome-inactivating protein ( RIP ) toxins from workss and Fungis were wholly assessed ( Kozlov et al. , 2006 ; Stirpe and Battelli, 2006 ) .
Briefly, the B concatenation binds to galactose/N-acetylgalactosamine-containing glycoproteins and glycolipids in eucaryotic cells. The binding to come up receptors can be inhibited by brain sugar or lactose in vitro. It appears that both ironss facilitate the incursion by endocytosis of the toxin into the cell. The B concatenation, nevertheless, aids the toxin in translocating to endosomal marks every bit good. Once in the cytosol, the A concatenation cleaves a individual A base from the 28S ribosomal ( Ribonucleic acid ) RNA within the 60S ribosomal fractional monetary unit, rendering it unable to adhere the elongation factor 2 which accordingly leads to an apprehension of protein synthesis. A individual A concatenation molecule can demobilize 1500 ribosomes per minute and kill the cell. In add-on to suppressing protein synthesis, ricin was shown to arouse programmed cell death, cause oxidative emphasis, release proinflammatory cytokines, modify cell membrane construction and map, and impair atomic DNA ( reviewed by Stirpe and Battelli, 2006 ) . Lipase activity of ricin was besides clearly shown ( Morlon-Guyot et al. , 2003 ) .
Toxicity
Toxicity to Laboratory Animals
Although the manner of action of ricin at the molecular degree is known, the mechanisms responsible for the clinical and deadly effects of the toxin are still inadequately understood. Representative carnal toxicity informations for ricin administered by different paths are shown in Table 1. The fluctuations in the acute toxicity values reported in the literature are chiefly due to mixture of the readyings used in the trials ( reviewed by Balint, 1974 ) . The symptoms of ricin poisoning manifest easy, normally 12 hour after disposal, and include instead sudden effusions of paroxysms and opisthotonos, followed by palsy of the respiratory centre, finally taking to decease. Causeless toxic condition is normally due to consumption of Castor beans ( for recent illustrations, see Aslani et al. , 2007 ; Soto-Blanco et al. , 2002 ) . Laboratory trials with seeds showed biddy to be the most immune species ( the lethal dosage was 14 g/kg ) ; sheep and Equus caballus were more sensitive ( deadly doses were 1.25 and 0.10 g/kg, severally ) . The toxin is pyrogenous in mammals ( Balint, 1993 ) . In the serum of animate beings treated with ricin, antibodies specific to ricin hold repeatedly been detected ( see, for illustration, Griffiths et al. , 2007 ) .
Ricin is extremely toxic upon injection and inspiration. Using transmittal negatron microscopy, Brown and White ( 1997 ) ( see besides Griffiths et al. , 1995b, 2007 ) examined the histopathological alterations in the lungs of rats upon ricin inspiration. The animate beings were exposed to an LCt30 ( the concentration in air that killed 30 % of the open animate beings ) of 11.21 mg/min/m3 dosage of the toxin. Necrotic alterations were
evident in the capillary endothelium and type I epithelial cells, accompanied by intraalveolar hydrops 12-15 H after exposure.
Table 1. Acute Toxicity of Ricin
Speciess, sex
Path
LD50 ( ?g/kg )
Minimal lethal dosage ( ?g/kg )
