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Toxins Oct 2017Ricin, a plant-derived toxin originating from the seeds of Ricinus communis (castor beans), is one of the most lethal toxins known, particularly if inhaled. Ricin is... (Review)
Review
Ricin, a plant-derived toxin originating from the seeds of Ricinus communis (castor beans), is one of the most lethal toxins known, particularly if inhaled. Ricin is considered a potential biological threat agent due to its high availability and ease of production. The clinical manifestation of pulmonary ricin intoxication in animal models is closely related to acute respiratory distress syndrome (ARDS), which involves pulmonary proinflammatory cytokine upregulation, massive neutrophil infiltration and severe edema. Currently, the only post-exposure measure that is effective against pulmonary ricinosis at clinically relevant time-points following intoxication in pre-clinical studies is passive immunization with anti-ricin neutralizing antibodies. The efficacy of this antitoxin treatment depends on antibody affinity and the time of treatment initiation within a limited therapeutic time window. Small-molecule compounds that interfere directly with the toxin or inhibit its intracellular trafficking may also be beneficial against ricinosis. Another approach relies on the co-administration of antitoxin antibodies with immunomodulatory drugs, thereby neutralizing the toxin while attenuating lung injury. Immunomodulators and other pharmacological-based treatment options should be tailored according to the particular pathogenesis pathways of pulmonary ricinosis. This review focuses on the current treatment options for pulmonary ricin intoxication using anti-ricin antibodies, disease-modifying countermeasures, anti-ricin small molecules and their various combinations.
Topics: Animals; Antitoxins; Humans; Lung Diseases; Ricin
PubMed: 28972558
DOI: 10.3390/toxins9100311 -
Current Topics in Microbiology and... 2012Ricin and Shiga toxins designated as ribosome inactivating proteins (RIPs) are RNA N-glycosidases that depurinate a specific adenine (A₄₃₂₄ in rat 28S rRNA) in... (Review)
Review
Ricin and Shiga toxins designated as ribosome inactivating proteins (RIPs) are RNA N-glycosidases that depurinate a specific adenine (A₄₃₂₄ in rat 28S rRNA) in the conserved α-sarcin/ricin loop of the large rRNA, inhibiting protein synthesis. Evidence obtained from a number of studies suggests that interaction with ribosomal proteins plays an important role in the catalytic activity and ribosome specificity of RIPs. This review summarizes the recent developments in identification of the ribosomal proteins that interact with ricin and Shiga toxins and the principles governing these interactions.
Topics: Enzyme Activation; Protein Binding; Ribosomal Proteins; Ribosome Inactivating Proteins; Ribosomes; Ricin; Shiga Toxins
PubMed: 21910078
DOI: 10.1007/82_2011_174 -
Biotechnology Advances 2015Ricin is a plant toxin with high bioterrorism potential due to its natural abundance and potency in inducing cell death. Early detection of the active toxin is essential... (Review)
Review
Ricin is a plant toxin with high bioterrorism potential due to its natural abundance and potency in inducing cell death. Early detection of the active toxin is essential for developing appropriate countermeasures. Here we review concepts for designing ricin detection methods, including mechanism of action of the toxin, advantages and disadvantages of current detection assays, and perspectives on the future development of rapid and reliable methods for detecting ricin in environmental samples.
Topics: Biological Assay; Bioterrorism; Enzyme-Linked Immunosorbent Assay; Protein Conformation; Ricin
PubMed: 25481398
DOI: 10.1016/j.biotechadv.2014.11.012 -
Toxins Jan 2021Ricin, a protein derived from the seeds of the castor bean plant (), is a highly lethal toxin that inhibits protein synthesis, resulting in cell death. The widespread...
Ricin, a protein derived from the seeds of the castor bean plant (), is a highly lethal toxin that inhibits protein synthesis, resulting in cell death. The widespread availability of ricin, its ease of extraction and its extreme toxicity make it an ideal agent for bioterrorism and self-poisoning. Thus, a rapid, sensitive and reliable method for ricin identification in clinical samples is required for applying appropriate and timely medical intervention. However, this goal is challenging due to the low predicted toxin concentrations in bio-fluids, accompanied by significantly high matrix interferences. Here we report the applicability of a sensitive, selective, rapid, simple and antibody-independent assay for the identification of ricin in body fluids using mass spectrometry (MS). The assay involves lectin affinity capturing of ricin by easy-to-use commercial lactose-agarose (LA) beads, following by tryptic digestion and selected marker identification using targeted LC-MS/MS (Multiple Reaction Monitoring) analysis. This enables ricin identification down to 5 ng/mL in serum samples in 2.5 h. To validate the assay, twenty-four diverse naive- or ricin-spiked serum samples were evaluated, and both precision and accuracy were determined. A real-life test of the assay was successfully executed in a challenging clinical scenario, where the toxin was identified in an abdominal fluid sample taken 72 h post self-injection of castor beans extraction in an eventual suicide case. This demonstrates both the high sensitivity of this assay and the extended identification time window, compared to similar events that were previously documented. This method developed for ricin identification in clinical samples has the potential to be applied to the identification of other lectin toxins.
Topics: Humans; Biomarkers; Chromatography, Liquid; Limit of Detection; Reproducibility of Results; Ricin; Tandem Mass Spectrometry; Time Factors; Workflow
PubMed: 33499033
DOI: 10.3390/toxins13020079 -
Sensors (Basel, Switzerland) May 2022Ricin and abrin are phytotoxins that can be easily used as biowarfare and bioterrorism agents. Therefore, developing a rapid detection method for both toxins is of great...
Ricin and abrin are phytotoxins that can be easily used as biowarfare and bioterrorism agents. Therefore, developing a rapid detection method for both toxins is of great significance in the field of biosecurity. In this study, a novel nanoforest silicon microstructure was prepared by the micro-electro-mechanical systems (MEMS) technique; particularly, a novel microfluidic sensor chip with a capillary self-driven function and large surface area was designed. Through binding with the double antibodies sandwich immunoassay, the proposed sensor chip is confirmed to be a candidate for sensing the aforementioned toxins. Compared with conventional immunochromatographic test strips, the proposed sensor demonstrates significantly enhanced sensitivity (≤10 pg/mL for both toxins) and high specificity against the interference derived from juice or milk, while maintaining good linearity in the range of 10-6250 pg/mL. Owing to the silicon nanoforest microstructure and improved homogeneity of the color signal, short detection time (within 15 min) is evidenced for the sensor chip, which would be helpful for the rapid tracking of ricin and abrin for the field of biosecurity.
Topics: Abrin; Microfluidics; Ricin; Silicon; Toxins, Biological
PubMed: 35591151
DOI: 10.3390/s22093461 -
Toxins Nov 2011The toxin ricin has long been understood to have potential for criminal activity and there has been concern that it might be used as a mass-scale weapon on a military... (Review)
Review
The toxin ricin has long been understood to have potential for criminal activity and there has been concern that it might be used as a mass-scale weapon on a military basis for at least two decades. Currently, the focus has extended to encompass terrorist activities using ricin to disrupt every day activities on a smaller scale. Whichever scenario is considered, there are features in common which need to be understood; these include the knowledge of the toxicity from ricin poisoning by the likely routes, methods for the detection of ricin in relevant materials and approaches to making an early diagnosis of ricin poisoning, in order to take therapeutic steps to mitigate the toxicity. This article will review the current situation regarding each of these stages in our collective understanding of ricin and how to defend against its use by an aggressor.
Topics: Administration, Oral; Animals; Chemical Warfare Agents; Eating; Humans; Inhalation Exposure; Injections, Intramuscular; Ricin
PubMed: 22174975
DOI: 10.3390/toxins3111373 -
Current Topics in Microbiology and... 2012Ricin toxin is an extraordinarily potent inducer of cell death and inflammation. Ricin is also a potent provocateur of the humoral immune system, eliciting a mixture of... (Review)
Review
Ricin toxin is an extraordinarily potent inducer of cell death and inflammation. Ricin is also a potent provocateur of the humoral immune system, eliciting a mixture of neutralizing, non-neutralizing and even toxin-enhancing antibodies. The characterization of dozens of monoclonal antibodies (mAbs) against the toxin's enzymatic (RTA) and binding (RTB) subunits has begun to reveal fundamental insights into the underlying mechanisms by which antibodies neutralize (or fail to neutralize) ricin in systemic and mucosal compartments. This information has had immediate applications in the design, development and evaluation of ricin subunit vaccines and immunotherapeutics.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Neutralizing; Epitopes, B-Lymphocyte; Humans; Immunity, Mucosal; Protein Binding; Ricin
PubMed: 22113742
DOI: 10.1007/82_2011_193 -
FEBS Letters Jun 1994Ricin and Shiga toxin belong to a group of protein toxins with targets in the cytosol. These toxins consist of one moiety that binds the toxin molecule to cell surface... (Review)
Review
Ricin and Shiga toxin belong to a group of protein toxins with targets in the cytosol. These toxins consist of one moiety that binds the toxin molecule to cell surface receptors, and another enzymatically active moiety that enters the cytosol after endocytic uptake of the toxin. The toxins are of current interest in relation to disease and the construction of immunotoxins. Moreover, they have proven useful to investigate mechanisms of endocytosis and to follow intracellular pathways of transport. Some of the recent results obtained with ricin and Shiga toxin are discussed.
Topics: Bacterial Toxins; Cell Membrane; Endocytosis; Endoplasmic Reticulum; Golgi Apparatus; Humans; Ricin; Shiga Toxins
PubMed: 8206167
DOI: 10.1016/0014-5793(94)00281-9 -
Toxins Apr 2017Both ricin and Shiga holotoxins display no ribosomal activity in their native forms and need to be activated to inhibit translation in a cell-free translation inhibition...
Both ricin and Shiga holotoxins display no ribosomal activity in their native forms and need to be activated to inhibit translation in a cell-free translation inhibition assay. This is because the ribosome binding site of the ricin A chain (RTA) is blocked by the B subunit in ricin holotoxin. However, it is not clear why Shiga toxin 1 (Stx1) or Shiga toxin 2 (Stx2) holotoxin is not active in a cell-free system. Here, we compare the ribosome binding and depurination activity of Stx1 and Stx2 holotoxins with the A1 subunits of Stx1 and Stx2 using either the ribosome or a 10-mer RNA mimic of the sarcin/ricin loop as substrates. Our results demonstrate that the active sites of Stx1 and Stx2 holotoxins are blocked by the A2 chain and the B subunit, while the ribosome binding sites are exposed to the solvent. Unlike ricin, which is enzymatically active, but cannot interact with the ribosome, Stx1 and Stx2 holotoxins are enzymatically inactive but can interact with the ribosome.
Topics: Ribosomes; Ricin; Shiga Toxin 1; Shiga Toxin 2
PubMed: 28398250
DOI: 10.3390/toxins9040133 -
International Journal of Biological... Jul 2018Castor cake is a by-product of the extraction of oil from from seeds of castor plants (Ricinus communis). This by-product contains high levels of proteins, but a toxic...
Castor cake is a by-product of the extraction of oil from from seeds of castor plants (Ricinus communis). This by-product contains high levels of proteins, but a toxic protein, ricin, limits its use as an animal feed. Ricin can be efficiently inactivated by treatment with calcium oxide (CaO), which can be evaluated by a cytotoxicity assay using LLC-MK2 cells. The mechanism by which the CaO treatment inactivates ricin, however, is unclear. We report the structural changes responsible for ricin inactivation. Purified ricin was treated with 0.6% CaO and then analyzed by mass spectrometry. This treatment degraded the ricin at preferential sites. The aqueous CaO solution had a pH >12, which preferentially cleaved asparagine residues, followed by glutamine, serine and glycine residues. The alkaline pH affected the tertiary structure of the ricin, cleaving its polypeptide chains and thereby eliminating its cytotoxic activity.
Topics: Animals; Calcium Compounds; Cell Line; Cytotoxins; Oxides; Proteomics; Ricin
PubMed: 29522821
DOI: 10.1016/j.ijbiomac.2018.03.024