Ricin is a highly toxic plant protein with two peptide chains. It mainly exists in castor beans. The toxin is easy to damage the liver, kidney and other parenchymal organs, hemorrhage, degeneration, necrosis lesions. And can agglutinate and dissolve erythrocytes, inhibit paralysis of cardiovascular and respiratory center, is one of the main causes of death.

Mice intravenous LD50 value of 2.7 μg / kg, intraperitoneal injection of 7 ~ 10 μg / kg; on the dog LD50 value of 0.6 μg / kg; lethal dose of about 7mg.

Ricin in addition to poisoned water and food through the gastrointestinal tract poisoning, can be used as an international espionage intelligence agents and terrorists to carry out assassination and sabotage of toxin warfare weapons. In 1978, international spies in London used the tip of an umbrella filled with ricin to assassinate a person in a public place, and a person who was assassinated was poisoned to death. There were similar incidents and occurrences in Paris, France, at the same time.

Research History, Physical and Chemical Properties, Toxicology, Toxicity Mechanisms, Inhibition of Protein Synthesis, Induction of Cytokine Damage, Lipid Peroxidation Damage, Induction of Apoptosis, Rescue, Research History Due to its intense toxicity, diagnosis, treatment difficulties, as early as during the First World War, the U.S. military as a candidate for chemical warfare agent for extensive research, and had produced 1,700 kilograms of the crude ricin product. (code name WA). Ricin (Figure 1) Physical and chemical properties Ricin's primary and secondary structure has been clear, by the A, B two chains. A chain than the B chain is slightly shorter than the two chains to a disulfide bond between the line. It contains *** valence bonded sugar molecules, the main components of sugar are mannose, glucose and galactose. The molecular weight is 66,000. in 0.1 g molecules of galactose solution, the toxin can be stored in a freezer for several months without loss of activity, but is easily inactivated by boiling. Ricin is a plant glycoprotein extracted from castor beans with a molecular weight of 64,000. the toxin consists of two polypeptide chains, A and B, which are linked by a disulfide bond. At present, the amino acid sequences of the A and B chains as well as the secondary structure have been basically clarified. The toxin B chain contains two galactose or galactose residue binding sites, which can bind to galactose residue-containing receptors on the cell surface and enter the cytoplasm through invagination to exert toxic effects. Ricin A and B chains also contain one and two sugar branched chains, respectively, with mannose residues at the ends of the chains, which can bind to reticuloendothelial cells, especially macrophages. The latter cell surface is rich in mannose receptors, which can preferentially take up ricin, which is important for the toxin to play an important role in biological functions. Castor Seed Toxicology Ricin is a cytotoxin. When the toxin enters the body, the A and B chains are separated. the A chain enters the cytoplasm through permeation through the cell membrane, mainly inactivating the inhibition of ribosomes in eukaryotic cells, thus inhibiting protein synthesis. the B chain binds to the cell surface and transfers to the cell through invagination, which promotes the entry of A chain into the cytosol. Ricin has a significant inhibitory effect on mouse Ehrlich ascites tumor cells, LD12 leukemia, B16 nevus tumor and Levins lung cancer cells, killing cancer cells mainly by inhibiting protein synthesis. In addition, it is found that it has synergistic effect with other drugs, such as ricin and adriamycin (adriamycin) combined to kill leukemia cells has a significant synergistic effect. Clinical manifestations The LD50 value of mice is 2.7μg/kg by intravenous injection, and 7-10μg/kg by intraperitoneal injection; the LD50 value of dogs is 0.6μg/kg; the lethal dose of human is about 7mg; the symptoms appear a few hours after the poisoning. In the early stage, there are mental instability, nausea and vomiting, abdominal pain, diarrhea, blood in the stool; followed by dehydration, blood pressure drop, shock and drowsiness; in severe cases, convulsions, coma, teeth closed; finally, death due to circulatory failure. A few patients may have fever, jaundice, blood in stool, proteinuria, anuria or hematuria, and eventually die of acidosis and uremia. The toxin is easy to damage the liver, kidney and other parenchymal organs, hemorrhage, degeneration, necrotic lesions. And can agglutinate and dissolve red blood cells, inhibit paralysis of cardiovascular and respiratory centers, is one of the main causes of death. Toxicity Mechanism of action Inhibition of protein synthesis Ricin is strongly cytotoxic, belonging to the protein synthesis inhibitor or ribosome inactivator, which is the main reason for the construction of immunotoxins, set to ricin. The mechanism of synthesis was clarified in the 1970s. First, the toxin relies on a galactose binding site on the B chain to bind to a receptor containing terminal galactose residues on the cell surface, facilitating the entry of the entire toxin molecule into the cell in an invaginated manner to form an intracellular vesicle from which the toxin passes into the cytoplasm, and the subsequent reductive cleavage of the disulfide bonds between the protein chains, freeing the A chain. the A chain is a protease that acts on the 28S of the large subunit of the ribosomal 60S of the eukaryotic cells rRNA, hydrolyzes the adenosine N-glycoside bond at the A4324 site, causing it to de-adenine, lose its anti-RNAase resistance and be degraded, and not be able to bind to the elongation factor (EF-2), which interferes with the formation of the ribosomal, EF-2, and guanosine adenosine triphosphate (GTP) complexes, leading to inhibition of protein synthesis and eventual cell death. It has been brought to the attention of researchers that ① The B chain has an important role in promoting the A chain to exert toxicity. ② Reductive cleavage of interchain disulfide bonds in the cell plays an important role in the toxin's toxic effects. ③ Recent studies have shown that the galactose binding site on the B chain is also involved in the in vivo toxicity of the toxin. Induction of cytokine damage The mechanism of cytokine induction by ricin is now mostly thought to be through *** lymphoid cell production. The main ones are macrophages and hepatic Kupffer′s cells. These cells contain mannose receptors on their surface that bind specifically to the three terminal mannose residues in the ricin molecule and are preferentially taken up. Ricin induces cytokine secretion in a dose- and time-dependent manner. Whether the toxin induces the production of other cytokines and whether there is a net immunoregulatory effect among the cytokines remains to be explored. In 1986, Tracey et al. found that intestinal damage in ricin-poisoned rats was similar to that in TNF/Chchectin-treated rats.In 1991, Nadkami and Deshphude suggested that many of the phenomena following ricin poisoning, such as fever, hepatic hemorrhagic necrosis, ascites, oozing of pleural fluid, hemorrhagic necrotic inflammation of the intestinal tract, and other early acute reactions are In 1993, Licastro et al. detected that ricin induced the secretion of TNF-α and IL-1β from peripheral blood mononuclear cells cultured in vitro, and low levels of TNF-α were also detected in the plasma of ricin-poisoned rats. 1994 Mudlooon et al. found that the in vivo injection of anti-TNF-α and IL-1β in peripheral blood mononuclear cells induced the secretion of TNF-α and IL-1β, and low levels of TNF-α were also detected in the plasma of rats poisoned by ricin. In 1994, Mudlooon et al. found that the injection of anti-TNF antibodies significantly reduced the oxidative damage caused by ricin in mice, and in 1997, Dong Juying et al. reported the immunohistochemical localization of TNF in the livers of ricin-poisoned mice. Another example of the involvement of cytokines in organismal damage is that the side effects experienced by patients in phase 1 and 2 clinical trials of ricin-constructed immunotoxins, including fever, myalgia, and capillary leakage syndrome, could be alleviated by blocking or antagonizing the function of these cytokines. Ricin toxicity has a clear dose-dependent, toxin-induced cytokine production, causing lipid peroxidation damage in vivo as well as inducing apoptosis of target cells, etc. are in the small dose range, while large doses of ricin is still mainly manifested in the inhibition of protein synthesis toxicity. Toxin-induced cytokine production and lipid peroxidation damage in vivo are related to the specific uptake of mannose residues at the end of its sugar chain by macrophages and activation of macrophages, which are secondary to toxin damage. Theoretical studies on the induction of apoptosis by protein synthesis inhibitors such as ricin may have an important complementary value to existing theories of apoptosis. Lipid peroxidation injury The interaction of ricin with macrophages not only induces cellular immunity, but also induces the production of free radicals and reactive oxygen species, causing lipid peroxidation.In 1991, Muldoon and Stohes found that ricin induced lipid peroxidation in mice, which resulted in an increase in the levels of malondialdehyde, formaldehyde, and acetone in the urine.A study in 1992 showed that that the intensity of lipid peroxidation (MDA content), the reduction of reduced glutathione and the extent of DNA single-strand breaks in all organs were most intense 36 hours after toxin poisoning and that the most severe damage was observed in the liver. Combined with previous studies that glutathione administration can partially counteract the effects of lethal doses of the toxin and has a potential chemoprotective effect, Muldoon et al. concluded that the oxidative effects induced by ricin can be attributed to the mechanism of toxicity of ricin. TNF-α antibody, iron ions play an important role in regulating ricin-induced lipid peroxidation and oxidative damage. Administration of anti-TNF-α antibodies to mice significantly reduced urinary malondialdehyde, formaldehyde, and acetone levels. Addition of iron ions and desferrioxamine increased and decreased the levels of ricin-induced lipid peroxidation, respectively. The mechanism of ricin-induced oxidative damage in vivo remains to be explored in greater depth. Induction of apoptosis Necrosis and apoptosis are two modes of cell death. Among the three main categories of factors that cause apoptosis, toxins, anticancer drugs are one of them. Previously, it was believed that chemotherapeutic drugs kill tumor cells by causing irreversible metabolic disorders in target cells, but in recent years, it is believed that the therapeutic efficacy is achieved by changing the physiological environment and inducing PCD (programmed cell death) in cells. In 1989, Leek et al. reported that in the study of intestinal pathology of ricin poisoning, apoptosis-like changes in the cytoplasm of intestinal epithelial cells were observed by immunohistochemistry and electron microscopy, and in 1990, Waring reported that ricin induced DNA fragmentation in macrophages and immature T cells, which is considered to be a biochemical factor related to apoptosis. In 1991, they reported that ricin induced apoptosis-like morphological changes in epithelial cells, and in 1996, Fu et al. reported that ricin induced apoptosis in thyroid and spleen cells in mice. The mechanism of apoptosis induced by protein synthesis inhibitors, such as ricin, is not related to their inhibition of protein synthesis and does not require the participation of Ca2+-dependent endonuclease, but is related to their elevation of intracellular inositol triphosphate levels. In addition, it has been reported that macrophage adhesion prevents the occurrence of ricin-induced macrophage apoptosis. The anti-phagocytic effect of ricin may directly lead to DNA breaks and induction of apoptosis. Data suggest that deleterious factors that cause cell necrosis can lead to cell necrosis at high intensities, but cause cells to undergo apoptosis at lower intensities. Ricin-induced apoptosis was also found to be dose-dependent. In conclusion, the induction of apoptosis by ricin does not contradict the traditional use of ricin as an inhibitor of protein synthesis. Treatment Immediately wash the stomach with potassium permanganate or charcoal suspension, followed by oral salt laxatives and high *** and other first aid measures to expel unabsorbed poison. Oral milk, egg white and gum arabic should be given to protect the gastric mucosa. In case of coma, drowsiness and other symptoms, subcutaneous injection of colamine, sodium camphor sulfonate, etc., and digitalis preparations can be used if necessary. If water loss occurs due to massive vomiting or severe diarrhea, large amounts of 5% glucose saline or low molecular dextrose should be administered in a timely manner to prevent dehydration leading to shock and to facilitate the dilution and discharge of toxins. Pay attention to correcting acidosis, and give sedatives such as phenobarbital when convulsions occur. When possible, early injection of anticastor serum and blood transfusion and other therapeutic measures. Potassium permanganate