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Intramuscular Ricin Poisoning of Mice Leads to Widespread Damage in the Heart, Spleen, and Bone Marrow

1
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100, Israel
2
Veterinary Center for Preclinical Research, Israel Institute for Biological Research, Ness-Ziona 76100, Israel
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(6), 344; https://doi.org/10.3390/toxins11060344
Received: 2 May 2019 / Revised: 11 June 2019 / Accepted: 13 June 2019 / Published: 16 June 2019
(This article belongs to the Collection Toxic and Pharmacological Effect of Plant Toxins)
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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. View Full-Text
Keywords: ricin; intramuscular; heart; cardiomyocytes; spleen; bone marrow; thrombocytopenia; coagulopathy; hemorrhages ricin; intramuscular; heart; cardiomyocytes; spleen; bone marrow; thrombocytopenia; coagulopathy; hemorrhages
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Sapoznikov, A.; Rosner, A.; Falach, R.; Gal, Y.; Aftalion, M.; Evgy, Y.; Israeli, O.; Sabo, T.; Kronman, C. Intramuscular Ricin Poisoning of Mice Leads to Widespread Damage in the Heart, Spleen, and Bone Marrow. Toxins 2019, 11, 344.

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