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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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/12/12/784 |
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| author | Sarah J. Whitfield Debbie B. Padgen Simon Knight Robert J. Gwyther Jane L. Holley Graeme C. Clark A. Christopher Green |
| author_facet | Sarah J. Whitfield Debbie B. Padgen Simon Knight Robert J. Gwyther Jane L. Holley Graeme C. Clark A. Christopher Green |
| author_sort | Sarah J. Whitfield |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T14:14:45Z |
| format | Article |
| id | doaj.art-91f5e8e7b8104a3b9785c267cd1d92aa |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T14:14:45Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-91f5e8e7b8104a3b9785c267cd1d92aa2023-11-20T23:56:06ZengMDPI AGToxins2072-66512020-12-01121278410.3390/toxins12120784Establishment of a Novel Oral Murine Model of Ricin Intoxication and Efficacy Assessment of Ovine Ricin AntitoxinsSarah J. Whitfield0Debbie B. Padgen1Simon Knight2Robert J. Gwyther3Jane L. Holley4Graeme C. Clark5A. Christopher Green6CBR Division, Dstl-Porton Down, Salisbury SP4 0JQ, UKCBR Division, Dstl-Porton Down, Salisbury SP4 0JQ, UKCBR Division, Dstl-Porton Down, Salisbury SP4 0JQ, UKCBR Division, Dstl-Porton Down, Salisbury SP4 0JQ, UKCBR Division, Dstl-Porton Down, Salisbury SP4 0JQ, UKCBR Division, Dstl-Porton Down, Salisbury SP4 0JQ, UKCBR Division, Dstl-Porton Down, Salisbury SP4 0JQ, UKRicin, 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.https://www.mdpi.com/2072-6651/12/12/784<i>Ricinus communis</i>ricinovineantitoxinantibodyIgG |
| spellingShingle | Sarah J. Whitfield Debbie B. Padgen Simon Knight Robert J. Gwyther Jane L. Holley Graeme C. Clark A. Christopher Green Establishment of a Novel Oral Murine Model of Ricin Intoxication and Efficacy Assessment of Ovine Ricin Antitoxins Toxins <i>Ricinus communis</i> ricin ovine antitoxin antibody IgG |
| title | Establishment of a Novel Oral Murine Model of Ricin Intoxication and Efficacy Assessment of Ovine Ricin Antitoxins |
| title_full | Establishment of a Novel Oral Murine Model of Ricin Intoxication and Efficacy Assessment of Ovine Ricin Antitoxins |
| title_fullStr | Establishment of a Novel Oral Murine Model of Ricin Intoxication and Efficacy Assessment of Ovine Ricin Antitoxins |
| title_full_unstemmed | Establishment of a Novel Oral Murine Model of Ricin Intoxication and Efficacy Assessment of Ovine Ricin Antitoxins |
| title_short | Establishment of a Novel Oral Murine Model of Ricin Intoxication and Efficacy Assessment of Ovine Ricin Antitoxins |
| title_sort | establishment of a novel oral murine model of ricin intoxication and efficacy assessment of ovine ricin antitoxins |
| topic | <i>Ricinus communis</i> ricin ovine antitoxin antibody IgG |
| url | https://www.mdpi.com/2072-6651/12/12/784 |
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