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

Abstract

BackgroundRicin (also called RCA-II or RCA60), 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.Methods and FindingsIn 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 t1/2α of 4 min and a slower t1/2β 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.ConclusionsThe 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.

Determination of alkaloid compounds of Ricinus communis by using gas chromatography- mass spectroscopy (GC-MS)

“…Diethyl ester, 1.1.3.3.5.5.7.7.9.9.11.11.13.13.15.15 hexadecamethyl, Triethyl citrate, Diethyl Phthalate, and 3-Octadecene (Figures 5 to 11). The identified phytocompounds have the property of antioxidant and antimicrobial activities (He, 2010;Deus-de-Oliveira, 2011).…”

“…Low molecular proteins, 2S albumins, have been identified as the main allergenic compounds (Thorpe et al, 1988;Bashir et al, 1998;Deus-de-Oliveira et al, 2011). Experimental intoxication studies underline the major contribution of ricin as compared to other hazardous compounds found in the seeds (He, 2010). The oil and seed have been used as folk remedies for warts, cold tumors, indurations of the abdominal organs, whitlows, lacteal tumors, indurations of the mammary gland, corns, and moles, etc.…”

Analysis of Castor by ELISAs that Distinguish Ricin and Ricinus communis agglutinin (RCA)

“…It is a highly potent toxin, with a mean lethal oral dose of 29.5 mg/kg body weight in outbred mice [6] and estimated as 1-20 mg/kg body weight on the basis of analysis of human intoxications [7]. In addition to ricin, the castor seed also contains Ricinus communis agglutinin (RCA), a tetrameric protein that is homologous to ricin but much less toxic [8].…”

“…Previous research identified means to distinguish gene expression of ricin and RCA [9], but this approach is not applicable for protein levels. The development of monoclonal antibodies (mAbs) to determine castor agglutinins was previously reported and applied to food analyses [10][11][12][13] and ricin toxicokinetics [6]. Discrimination between ricin and RCA-1 is not critical for screening of food samples, as neither ricin nor RCA should be present.…”

Interação biológica de membranas poliméricas bioativas em falhas ósseas induzidas em tíbias de coelhos

“…No entanto, a proposta do uso de massa moldável para preencher falha óssea mostrouse possível e promissora, muito embora o enxerto ósseo esponjoso autógeno ainda seja considerado padrão ouro (FARDIN, 2010). He et al (2010) citaram o potencial tóxico da ricina e ricinina presente na mamona, que podem causar hemaglutinação e toxicidade nervosa.…”