Establishment of a Novel Oral Murine Model of Ricin Intoxication and Efficacy Assessment of Ovine Ricin Antitoxins

Ricin, produced from the castor beans of <i>Ricinus communis</i>, is a cytotoxin that exerts its action by inactivating ribosomes and causing cell death. Accidental (e.g., ingestion of castor beans) and/or intentional (e.g., suicide) exposure to ricin through the oral route is an area of...

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Bibliographic Details
Main Authors: Sarah J. Whitfield, Debbie B. Padgen, Simon Knight, Robert J. Gwyther, Jane L. Holley, Graeme C. Clark, A. Christopher Green
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Toxins
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Online Access:https://www.mdpi.com/2072-6651/12/12/784
Description
Summary:Ricin, produced from the castor beans of <i>Ricinus communis</i>, is a cytotoxin that exerts its action by inactivating ribosomes and causing cell death. Accidental (e.g., ingestion of castor beans) and/or intentional (e.g., suicide) exposure to ricin through the oral route is an area of concern from a public health perspective and no current licensed medical interventions exist to protect from the action of the toxin. Therefore, we examined the oral toxicity of ricin in Balb/C mice and developed a robust food deprivation model of ricin oral intoxication that has enabled the assessment of potential antitoxin treatments. A lethal oral dose was identified and mice were found to succumb to the toxin within 48 h of exposure. We then examined whether a despeciated ovine F(ab′)<sub>2</sub> antibody fragment, that had previously been demonstrated to protect mice from exposure to aerosolised ricin, could also protect against oral intoxication. Mice were challenged orally with an LD<sub>99</sub> of ricin, and 89 and 44% of mice exposed to this otherwise lethal exposure survived after receiving either the parent anti-ricin IgG or F(ab′)<sub>2</sub>, respectively. Combined with our previous work, these results further highlight the benefit of ovine-derived polyclonal antibody antitoxin in providing post-exposure protection against ricin intoxication.
ISSN:2072-6651