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Inactivation of ricin by constituents present in a skin decontamination lotion.
van den Berg, R M; Joosen, M J A; Savransky, V; Cochrane, L; Noort, D.
Afiliação
  • van den Berg RM; TNO Defense, Safety and Security, CBRN Protection, Lange Kleiweg 137, 2288, GJ, Rijswijk, the Netherlands. Electronic address: roland.vandenberg@tno.nl.
  • Joosen MJA; TNO Defense, Safety and Security, CBRN Protection, Lange Kleiweg 137, 2288, GJ, Rijswijk, the Netherlands.
  • Savransky V; Emergent BioSolutions, Emergent Prod. Dev. Gaithersburg, 300 Professional Drive, Gaithersburg, MD, 20879, USA.
  • Cochrane L; Emergent BioSolutions, Emergent Prod. Dev. Gaithersburg, 300 Professional Drive, Gaithersburg, MD, 20879, USA.
  • Noort D; TNO Defense, Safety and Security, CBRN Protection, Lange Kleiweg 137, 2288, GJ, Rijswijk, the Netherlands.
Chem Biol Interact ; 365: 110055, 2022 Sep 25.
Article em En | MEDLINE | ID: mdl-35963314
Ricin is a proteinaceous toxin, listed on the schedules of both the chemical and biological weapons conventions. The ease of accessibility to the Ricinus communis plant and toxin extraction makes ricin a viable concern for use of intentional release and causal effects. The adverse effects following exposure to the toxin are caused by the bipartite molecular structure of ricin which allows binding to the mammalian cell surface, enter via endocytic uptake, and deliver the catalytically active polypeptide into the cell cytosol where it irreversibly inhibits protein synthesis, causing cell death. In the present study, the inactivation effectiveness of RSDL® (Reactive Skin Decontamination Lotion) and its individual inactivating constituents (Potassium 2,3-butanedione monoximate (KBDO) and 2,3-butanedione (DAM)) was evaluated for ricin using a number of read out systems including a cytotoxicity assay, quantitative sandwich ELISA test, and a mass spectrometry-based assay. The results demonstrate that RSDL is able to abolish ricin activity after an incubation time of 30 min as determined in the cytotoxicity assay, and after 2 min as determined in the ELISA assay. Mass spectrometric analysis provided evidence that RSDL is able to induce cleavage of the disulfide linkage between the A- and B- polypeptide chain of ricin which is crucial to the inactivation of the toxin, but this seems not the only mechanism of inactivation. Follow on studies would assist to elucidate the details of the toxin inactivation because it is possible that additional generic mechanisms are in place for denaturation with the RSDL lotion components. This may also provide a promise for testing and inactivation with RSDL of other protein toxins.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ricina Limite: Animals Idioma: En Revista: Chem Biol Interact Ano de publicação: 2022 Tipo de documento: Article País de publicação: Irlanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ricina Limite: Animals Idioma: En Revista: Chem Biol Interact Ano de publicação: 2022 Tipo de documento: Article País de publicação: Irlanda