Ricin Toxicokinetics and Its Sensitive Detection in Mouse Sera or Feces Using Immuno-PCR

• Published in: PloS one 2010-09, Vol.5 (9), p.e12858
• Main Authors: He, Xiaohua, McMahon, Stephanie, Henderson, Thomas D, Griffey, Stephen M, Cheng, Luisa W, Hansen, Immo A
• Format: Article
• Language: English
• Subjects: Agriculture; Analysis; Animals; antibodies; Antigens; Assaying; Beans; Biological properties; Biological samples; Biotechnology; blood flow; castor beans; Chromatography; detection limit; Diagnostic systems; Etiology; Feces; Feces - chemistry; Female; Food contamination; food matrix; Gene expression; half life; histopathology; Immunoassay - methods; In vitro methods and tests; In vivo methods and tests; Ingestion; Intestine; Intoxication; Intravenous administration; intravenous injection; Lectins; Lesions; Lymph nodes; Lymphatic system; Mass spectrometry; Metabolism; Methods; Mice; Molecular Biology; Neutralization; neutralization tests; Organs; Pancreas; Pathological effects; Pathology/Histopathology; pharmacokinetics; Pharmacology; Plant introductions; Poisoning; Polymerase Chain Reaction - methods; Public Health and Epidemiology; Radioactive half-life; Random Allocation; Ricin; Ricin - analysis; Ricin - blood; Ricin - pharmacokinetics; Ricin - toxicity; Ricinus communis; Ricinus communis - chemistry; Scientific imaging; Seeds; Sensitivity and Specificity; Spleen; Tissue Distribution; Toxicology; Toxins
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0012858

Ricin (also called RCA-II or RCA 60), one of the most potent toxins and documented bioweapons, is derived from castor beans of Ricinus communis . Several in vitro methods have been designed for ricin detection in complex food matrices in the event of intentional contamination. Recently, a novel Immuno-PCR (IPCR) assay was developed with a limit of detection of 10 fg/ml in a buffer matrix and about 10-1000-fold greater sensitivity than other methods in various food matrices. In order to devise a better diagnostic test for ricin, the IPCR assay was adapted for the detection of ricin in biological samples collected from mice after intoxication. The limit of detection in both mouse sera and feces was as low as 1 pg/ml. Using the mouse intravenous (iv) model for ricin intoxication, a biphasic half-life of ricin, with a rapid t 1/2 α of 4 min and a slower t 1/2 β of 86 min were observed. The molecular biodistribution time for ricin following oral ingestion was estimated using an antibody neutralization assay. Ricin was detected in the blood stream starting at approximately 6–7 h post- oral intoxication. Whole animal histopathological analysis was performed on mice treated orally or systemically with ricin. Severe lesions were observed in the pancreas, spleen and intestinal mesenteric lymph nodes, but no severe pathology in other major organs was observed. The determination of in vivo toxicokinetics and pathological effects of ricin following systemic and oral intoxication provide a better understanding of the etiology of intoxication and will help in the future design of more effective diagnostic and therapeutic methods.