Medical Countermeasures against Ricin Intoxication

Rasetti-Escargueil, Christine; Avril, Arnaud

doi:10.3390/toxins15020100

Cited by 9 publications

(6 citation statements)

References 120 publications

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“…The ricin toxin is the only bioterrorism agent classified by the CDC that is neither viral, nor bacterial (or designated as a specific threat with a bacterium, as is the case with C. parvum ) ( Appendix 3 ). The toxin is produced by Ricinus communis , the castor bean, and when extracted, it can be disseminated by a number of modalities including aerosol, injection, or ingestion pathways ( 121 ). Physical symptoms vary by route of intoxication.…”

Section: Miscellaneousmentioning

confidence: 99%

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Ophthalmic implications of biological threat agents according to the chemical, biological, radiological, nuclear, and explosives framework

Curran,

Devine,

Hartley

et al. 2024

Front. Med.

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As technology continues to evolve, the possibility for a wide range of dangers to people, organizations, and countries escalate globally. The United States federal government classifies types of threats with the capability of inflicting mass casualties and societal disruption as Chemical, Biological, Radiological, Nuclear, and Energetics/Explosives (CBRNE). Such incidents encompass accidental and intentional events ranging from weapons of mass destruction and bioterrorism to fires or spills involving hazardous or radiologic material. All of these have the capacity to inflict death or severe physical, neurological, and/or sensorial disabilities if injuries are not diagnosed and treated in a timely manner. Ophthalmic injury can provide important insight into understanding and treating patients impacted by CBRNE agents; however, improper ophthalmic management can result in suboptimal patient outcomes. This review specifically addresses the biological agents the Center for Disease Control and Prevention (CDC) deems to have the greatest capacity for bioterrorism. CBRNE biological agents, encompassing pathogens and organic toxins, are further subdivided into categories A, B, and C according to their national security threat level. In our compendium of these biological agents, we address their respective CDC category, systemic and ophthalmic manifestations, route of transmission and personal protective equipment considerations as well as pertinent vaccination and treatment guidelines.

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Section: Miscellaneousmentioning

confidence: 99%

“…If injected, myalgias and circulatory collapse are common. Ingested ricin typically causes abdominal pain, diarrhea, cramping, and dehydration ( 121 ). Ophthalmic implications of ricin toxin have yet to be described other than conjunctival injection.…”

Section: Miscellaneousmentioning

confidence: 99%

Ophthalmic implications of biological threat agents according to the chemical, biological, radiological, nuclear, and explosives framework

Curran,

Devine,

Hartley

et al. 2024

Front. Med.

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“…Compared to neutralizing antibodies that detoxify only before ricin enters cells [11], and antagonist peptides that are easily degraded in the body and not suitable for oral administration [12,13], small-molecule inhibitors have many advantages. They can act both before and after ricin enters the cells and are less susceptible to changes in the pH level inside the body and degradation [13]. Pteroic acid (PTA) is one of the most widely studied ricin inhibitors [14].…”

Section: Introductionmentioning

confidence: 99%

Identification and Biological Evaluation of a Novel Small-Molecule Inhibitor of Ricin Toxin

Yang,

Wei,

Cao

et al. 2024

Molecules

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The plant-derived toxin ricin is classified as a type 2 ribosome-inactivating protein (RIP) and currently lacks effective clinical antidotes. The toxicity of ricin is mainly due to its ricin toxin A chain (RTA), which has become an important target for drug development. Previous studies have identified two essential binding pockets in the active site of RTA, but most existing inhibitors only target one of these pockets. In this study, we used computer-aided virtual screening to identify a compound called RSMI-29, which potentially interacts with both active pockets of RTA. We found that RSMI-29 can directly bind to RTA and effectively attenuate protein synthesis inhibition and rRNA depurination induced by RTA or ricin, thereby inhibiting their cytotoxic effects on cells in vitro. Moreover, RSMI-29 significantly reduced ricin-mediated damage to the liver, spleen, intestine, and lungs in mice, demonstrating its detoxification effect against ricin in vivo. RSMI-29 also exhibited excellent drug-like properties, featuring a typical structural moiety of known sulfonamides and barbiturates. These findings suggest that RSMI-29 is a novel small-molecule inhibitor that specifically targets ricin toxin A chain, providing a potential therapeutic option for ricin intoxication.

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“…In the following hours or days, the toxin diffuses in the circulation leading to vascular collapse and progressive multiple organ failures, which may lead to death [ 9 ]. Currently, there is no effective treatment against ricin intoxication [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Autophagic Degradation Is Involved in Cell Protection against Ricin Toxin

Taisne

Mahtal

et al. 2023

Toxins

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Autophagy is a complex and highly regulated degradative process, which acts as a survival pathway in response to cellular stress, starvation and pathogen infection. Ricin toxin is a plant toxin produced by the castor bean and classified as a category B biothreat agent. Ricin toxin inhibits cellular protein synthesis by catalytically inactivating ribosomes, leading to cell death. Currently, there is no licensed treatment for patients exposed to ricin. Ricin-induced apoptosis has been extensively studied; however, whether its intoxication via protein synthesis inhibition affects autophagy is not yet resolved. In this work, we demonstrated that ricin intoxication is accompanied by its own autophagic degradation in mammalian cells. Autophagy deficiency, by knocking down ATG5, attenuates ricin degradation, thus aggravating ricin-induced cytotoxicity. Additionally, the autophagy inducer SMER28 (Small Molecule Enhancer 28) partially protects cells against ricin cytotoxicity, an effect not observed in autophagy-deficient cells. These results demonstrate that autophagic degradation acts as a survival response of cells against ricin intoxication. This suggests that stimulation of autophagic degradation may be a strategy to counteract ricin intoxication.

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Medical Countermeasures against Ricin Intoxication

Cited by 9 publications

References 120 publications

Ophthalmic implications of biological threat agents according to the chemical, biological, radiological, nuclear, and explosives framework

Ophthalmic implications of biological threat agents according to the chemical, biological, radiological, nuclear, and explosives framework

Identification and Biological Evaluation of a Novel Small-Molecule Inhibitor of Ricin Toxin

Autophagic Degradation Is Involved in Cell Protection against Ricin Toxin

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