Abstract
Ricin, a lethal toxin derived from castor oil beans, is a potential bio-threat due to its high availability and simplicity of preparation. Ricin is prepared according to simple recipes available on the internet, and was recently considered in terrorist, suicide, or homicide attempts involving the parenteral route of exposure. In-depth study of the morbidity developing from parenteral ricin poisoning is mandatory for tailoring appropriate therapeutic measures to mitigate ricin toxicity in such instances. The present study applies various biochemical, hematological, histopathological, molecular, and functional approaches to broadly investigate the systemic effects of parenteral intoxication by a lethal dose of ricin in a murine model. Along with prompt coagulopathy, multi-organ hemorrhages, and thrombocytopenia, ricin induced profound morpho-pathological and functional damage in the spleen, bone marrow, and cardiovascular system. In the heart, diffuse hemorrhages, myocyte necrosis, collagen deposition, and induction in fibrinogen were observed. Severe functional impairment was manifested by marked thickening of the left ventricular wall, decreased ventricular volume, and a significant reduction in stroke volume and cardiac output. Unexpectedly, the differential severity of the ricin-induced damage did not correlate with the respective ricin-dependent catalytic activity measured in the various organs. These findings emphasize the complexity of ricin toxicity and stress the importance of developing novel therapeutic strategies that will combine not only anti-ricin specific therapy, but also will target ricin-induced indirect disturbances.
Highlights
Ricin, a highly toxic protein isolated from the castor plant Ricinus communis, exerts its noxious effect by site-specific depurination of ribosomal 28S rRNA, which in turn leads to cessation of protein synthesis and cell death
Hematological analysis of blood samples collected from ricin-intoxicated mice revealed an increase over time in white blood cell (WBC) counts in general and in neutrophil counts in particular
Examination of coagulation rates in plasma samples collected at various time-points revealed a continuous prolongation in prothrombin time (PT) and activated partial thromboplastin time (APTT), and reduced coagulation performance, being evident already at 24 h post-exposure
Summary
A highly toxic protein isolated from the castor plant Ricinus communis, exerts its noxious effect by site-specific depurination of ribosomal 28S rRNA, which in turn leads to cessation of protein synthesis and cell death. Exposure to ricin can occur by oral ingestion, inhalation, or parenteral administration, though the features of poisoning and severity of toxicity vary markedly with the route of exposure. One of the few examples of parenteral ricin poisoning is that of Georgi Markov, a Bulgarian journalist who was assassinated in 1978 with a ricin-laden umbrella tip, which was used to stab his right thigh [11]. This case, though taking place several decades ago, is exceptional and very enlightening, as it has been comprehensively reviewed and provided a rudimentary chronological timeline for the clinical manifestations following parenteral ricin exposure in humans. At admission to a hospital approximately 35 h after the incident, local necrotic lymphadenopathy, elevated white cell counts, and a 6 cm diameter circular inflamed region of induration at the site of umbrella tip insert were documented
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