Abstract
Ricin and abrin belong to the group of type 2 ribosome-inactivating protein, which has a heterodimeric structure consisting of an A-chain linked by a disulfide bond to a B-chain. The B-chain facilitates internalization of the A-chain, which then exerts its toxic effects by inhibiting protein synthesis leading to cell death. These two plant toxins are highly toxic to human, and initial manifestations of ricin or abrin intoxication are generally nonspecific in nature. It is hence difficult to diagnose ricin and abrin poisoning through clinical symptoms alone. In view of their high toxicity, stability, relative ease of production and the worldwide availability of their source plants, ricin and abrin are considered to be potential chem-bio weapons of interests to terrorists. While the detection of ricin or abrin in adulterated food and beverages is relatively straightforward, the diagnosis of trace levels of either toxin in biofluid samples is challenged by their short half-life in circulation due to efficient sequestering of these toxins into the target organs. This chapter provides an overview of the latest developments, from the authors’ laboratory as well as from open literature, in diagnostic protocols for trace detection of ricin and abrin in biofluids as well as an extensive coverage of various experimental medical countermeasures being developed to tackle this rising threat in chem-bio terrorism.
References
Amukele TK, Roday S, Schramm VL. Ricin A-chain activity on stem-loop and unstructured DNA substrates. Biochemistry. 2005;44(11):4416–25.
Argent RH, Parrott AM, Day PJ, Roberts LM, Stockley PG, Lord JM, Radford SE. Ribosome-mediated folding of partially unfolded ricin A-chain. J Biol Chem. 2000;275:9263–9.
Audi J, Belson M, Patel M, Schier J, Osterloh J. Ricin poisoning: a comprehensive review. JAMA. 2005;294(18):2342–51.
Barbier J, Boucher C, Johannes L, Gillet D. Inhibitors of the cellular trafficking of ricin. Toxins. 2012;4:15–27.
Buonocore C, Alipour M, Omri A, Pucaj K, Smith MG, Suntres ZE. Treatment of ricin A-chain-induced hepatotoxicity with liposome-encapsulated N-acetylcysteine. J Drug Target. 2011;19(9):821–9.
Chen JK, Hung CH, Liaw YC, Lin JY. Identification of amino acid residues of abrin-a A chain is essential for catalysis and re-association with abrin-a B chain by site-directed mutagenesis. Protein Eng. 1997;10(7):827–33.
Dawson RM, Alderton MR, Wells D, Hartley PG. Monovalent and polyvalent carbohydrate inhibitors of ricin binding to a model of the cell-surface receptor. J Appl Toxicol. 2006;26:247–52.
Dickers KJ, Bradberry SM, Rice P, Griffiths GD, Vale JA. Abrin poisoning. Toxicol Rev. 2003;22(3):137–42.
Fan S, Wu F, Martiniuk F, Hale ML, Ellington AD, Tchou-Wong KM. Protective effects of anti-ricin A-chain RNA aptamer against ricin toxicity. World J Gastroenterol. 2008;14:6360–5.
Fodstad O, Olsnes S, Pihl A. Toxicity, distribution and elimination of the cancerostatic lectins abrin and ricin after parenteral injection into mice. Br J Cancer. 1976;34:418–25.
Foo LY, Sew WH, Chen HY, Loke WK. ELISA-based detection of ricin in blood and feces of rat following non-lethal exposure. Proceedings of the 7th Singapore International Symposium on Protection Against Toxic Substances, Singapore; 4–7 Dec 2012.
Franz DR, Jaax NK. Chapter 32 Ricin toxin. In: Sidell F, Takafuji T, Franz D, editors. Medical aspects of chemical and biological warfare. Washington, DC: Office of The Surgeon General, TMM Publications; 1997.
Funatsu G, Mise T, Matsuda H, Funatsu M. Isolation and characterisation of two constituent polypeptide chains of ricin E. Agric Biol Chem. 1978;41:851–9.
Gao S, Nie C, Wang J, Wang J, Kang L, Zhou Y, Wang JL. Colloidal gold-based immunochromatographic test strip for rapid detection of abrin in food samples. J Food Prot. 2012;75(1):112–7.
Garber EAC. Toxicity and detection of ricin and abrin in beverages. J Food Prot. 2008;71(9):1875–83.
Garber EAC, O’Brien TW. Detection of ricin in food using electrochemiluminescence-based technology. J AOAC Int. 2008;91(2):376–82.
Garber EAC, Walker JL, O’Brien TW. Detection of abrin in food using enzyme-linked immunosorbent assay and electrochemiluminescence technologies. J Food Prot. 2008;71(9):1868–74.
Griffith GD, Phillips GJ, Holley J. Inhalation toxicology of ricin preparations: animal models, prophylactic and therapeutic approaches to protection. Inhal Toxicol. 2007;19(10):873–87.
Griffiths GD, Knight SJ, Holley JL, Thullier P. Evaluation by ELISA of ricin concentration in fluids and tissues after exposure to aerosolised ricin, and evaluation of an immunochromatographic test for field diagnosis. J Clin Toxicol. 2013;3:162.
Han YH, Gao S, Xin WW, Kang L, Wang JL. A recombinant mutant abrin A chain expressed in Escherichia coli can be used as an effective vaccine candidate. Hum Vaccin. 2011;7(8):838–44.
He X, McMahon S, Henderson 2nd TD, Griffey SM, Cheng LW. Ricin toxicokinetics and its sensitive detection in mouse sera or feces using immuno-PCR. PloS One. 2010a;5(9):e12858.
He X, McMahon S, McKeon TA, Brandon DL. Development of a novel immune-PCR assay for detection of ricin in ground beef, liquid chicken egg, and milk. J Food Prot. 2010b;73(4):695–700.
Johnson RC, Lemire SW, Woolfitt AR, Ospina M, Preston KP, Olson CT, Barr JR. Quantification of ricinine in rat and human urine: a biomarker for ricin exposure. J Anal Toxicol. 2005;29:149–55.
Johnson RC, Zhou Y, Jain R, Lemire SW, Fox S, Sabourin P, Barr JR. Quantification of L-abrine in human and rat urine: a biomarker for the toxin abrin. J Anal Toxicol. 2009;33:77–84.
Kanamori-Kataoka M, Kato H, Uzawa H, Ohta S, Takei Y, Furuno M, Seto Y. Determination of ricin by nano liquid chromatography/mass spectrometry after extraction using lactose-immobilized monolithic silica spin column. J Mass Spectrom. 2011;46:821–9.
Keener WK, Rivera VR, Young CC, Poli MA. An activity-dependent assay for ricin and related RNA N-glycosidases based on electrochemiluminescence. Anal Biochem. 2006;357:200–7.
Lin JY, Ju ST, Wu HL, Tung TC. The binding of abrin and ricin by Erlich ascites tumor cells. Cancer Research 1973;33:2688–2691.
Mabley JG, Pacher P, Szabo C. Activation of the cholinergic anti-inflammatory pathway reduces ricin-induced mortality and organ failure in mice. Mol Med. 2009;15(5–6):166–72.
Maddaloni M, Cooke C, Wilkinson R, Stout AV, Eng L, Pincus SH. Immunological characteristics associated with the protective efficacy of antibodies to ricin. J Immunol. 2004;172:6221–8.
McHugh CA, Tammariello RF, Millard CB, Carra JH. Improved stability of a protein vaccine through elimination of a partially unfolded state. Protein Sci. 2004;13:2736–43.
Mu XH, Tong ZY, Hao LQ, Xu XL, Liu B, Tian YH. Assay of abrin by double antibody sandwich biotin-streptavidin ELISA. Immunol J. 2007–05.
Muldoon DF, Stohs SJ. Modulation of ricin toxicity in mice by biologically active substances. J Appl Toxicol. 1994;14(2):81–6.
O’Hara JA, Brey RN, Mantis NJ. Comparative efficacy of two leading candidate ricin toxin A subunit vaccines in mice. Clin Vaccine Immunol. 2013;20(6):789–94.
Olsnes S. The history of ricin, abrin and related toxins. Toxicon. 2004;44:361–70.
Pang Y-P, Park JG, Wang S, Vummenthala A, Mishra RK. Small-molecule inhibitor leads of ribosome-inactivating proteins developed using the doorstop approach. PLoS One. 2011;6(3):e17883.
Parker DT, Parker AC, Ramachandra CK. Ricin. Joint CBT technical data source book; Toxin agents. US Army dugway proving ground, Utah, Joint contact point directorate. 1996.
Pincus SH, Eng L, Cooke CL, Maddaloni M. Identification of hypoglycaemia in mice as a surrogate marker of ricin toxicoses. Comp Med. 2002;52(6):530–3.
Porter A, Phillips G, Smith L, Erwin-Cohen R, Tammariello R, Hale M, Dasilva L. Evaluation of a ricin vaccine candidate (RVEc) for human toxicity using an in vitro vascular leak assay. Toxicon. 2011;58:68–75.
Prigent J, Panigai L, Lamourette P, Sauvaire D, Devilliers K, Plaisance M, Volland H, Creminon C, Simon S. Neutralising antibodies against ricin toxin. PLoS One. 2011;6(5):e20166.
Reed BT, Opstad AM, Haavind A, TØngsager J. Serial ricinine levels in serum and urine after ricin intoxication. J Anal Toxicol. 2013. doi:10.1093/jat/bkt026.
Roxas-Duncan VI, Smith LA. Of beans and beads: ricin and abrin in bioterrorism and biocrime. J Bioterr Biodef. 2012;S7:002.
Roy CJ, Song K, Sivasubramani SK, Gardner DJ, Pincus SH. Animal models of ricin toxicosis. Curr Top Microbiol Immunol. 2012;357:243–57.
Smallshaw JE, Richardson JA, Vitetta ES. RiVax, a recombinant ricin subunit vaccine, protects mice against ricin delivered by gavage or aerosol. Vaccine. 2007;25:7459–69.
Stechmann B, Bai SK, Gobbo E, Lopez R, Merer G, Pinchard S, Panigai L, Tenza D, Raposo G, Beaumelle B. Inhibition of retrograde transport protects mice from lethal ricin challenge. Cell. 2010;141:231–42.
Surendranath K, Karande AA. A neutralizing antibody to the A chain of abrin inhibits abrin toxicity both in vitro and in vivo. Clin Vaccine Immunol. 2008;15(5):737–43.
Vitetta ES, Smallshaw JE, Coleman E, Jafri H, Foster C, Munford R, Schindler J. A pilot clinical trial of a recombinant ricin vaccine in normal humans. Proc Natl Acad U S A. 2006;103(7):2268–73.
Wahome PG, Ahlawat S, Mantis NJ. Identification of small molecules that suppress ricin-induced stress-activated signaling pathways. PLoS One. 2012;7(11):e49075.
Wang S, Feng J, Guo J, Guo L, Li Y, Sun Y, Qin W, Hu M, Han G, Shen B. A novel designed single domain antibody on 3-D structure of ricin A chain remarkably blocked ricin-induced cytotoxicity. Mol Immunol. 2006;43:1912–9.
Wang Y, Guo L, Zhao K, Chen J, Feng J, Sun Y, Li Y, Shen B. Novel chimeric anti-ricin antibody c4C13 with neutralizing activity against ricin toxicity. Biotechnol Lett. 2007;29:1811–6.
Wei CH, Hartman FC, Pfunderer P, Yang WC. Purification and characterization of the two major toxic proteins from seeds of Abrus precatorius. J Biol Chem. 1974;249:3061.
Worbs S, Kohler K, Pauly D, Avondet MA, Schaer M, Dorner MB, Dorner BG. Ricinus communis intoxications in human and veterinary medicine. Toxins. 2011;3:1332–72.
Zhou H, Zhou B, Ma H, Carney C, Janda KD. Selection and characterization of human monoclonal antibodies against abrin by phage display. Bioorg Med Chem Lett. 2007;17:5690–2.
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Chen, H., Foo, L., Loke, W. (2015). Ricin and Abrin: A Comprehensive Review of Their Toxicity, Diagnosis, and Treatment. In: Gopalakrishnakone, P. (eds) Biological Toxins and Bioterrorism. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6645-7_1-2
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DOI: https://doi.org/10.1007/978-94-007-6645-7_1-2
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Ricin and Abrin: A Comprehensive Review of Their Toxicity, Diagnosis, and Treatment- Published:
- 16 October 2015
DOI: https://doi.org/10.1007/978-94-007-6645-7_1-2
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Ricin and Abrin: A Comprehensive Review of Their Toxicity, Diagnosis, and Treatment- Published:
- 05 May 2014
DOI: https://doi.org/10.1007/978-94-007-6645-7_1-1