Ricin treatment

Therefore, the ability of TNF-a antibody to modulate ricin-induced urinary carbonyl excretion as well as hepatic lipid peroxidation, glutathione depletion, and DNA singlestrand breaks was assessed (Muldoon et al, 1994). Ricin-induced urinary MDA and FA were reduced significantly in mice receiving antibody (15,000 U/kg) 2 h before treatment with ricin (5 pg/kg). At 48 h following ricin treatment, MDA and FA concentrations in the urine of TNF antibody-treated... 

Ricin [9009-86-3], a phytotoxin found in the seeds of the castor oil plant Acinus communis, conjugated to murine monoclonal antibody (Immunogen Corp.), has been approved by the U.S. Food and Dmg Administration (FDA) for the treatment of patients with B-ceU leukemia and lymphoma (59). 

Other approaches to induce gastrointestinal discomfort have far more serious toxic effects. The chemical colchicine stops cell division (an antimitotic), producing severe nausea, vomiting, and dehydration, which can lead to delirium, neuropathy, and kidney failure. On the other hand, colchicine is used in the treatment of gout and has been studied as an anticancer agent because it stops cell division. Most toxic of all are plants that produce lectins, and the most toxic of these is the chemical ricin produced by castor beans. Only 5 to 6 seeds are necessary to kill a small child. Fortunately, following oral consumption much of the ricin is destroyed in the stomach. Ricin is extremely effective at stopping protein synthesis, so much so that direct exposure to only 0.1 pg/kg can be fatal. 

Laurent, G., D. Maraninchi, E. Gluckman, J.P Vernant, J.M. Derocq, M.H. Gaspard, B. Rio, M. Michalet, J. Reiffers, F. Dreyfus, et al.. Donor bone marrow treatment with TlOl Fab fragment-ricin A-chain immunotoxin prevents graft-versus-host disease. Bone Marrow Transplant, 1989. 4(4) 367-71. 

Many attempts have been made to link monoclonal antibodies specific for antigenic determinants on cancer cells to protein toxins such as ricin (Box 29-A). It is hoped that this may provide an effective way of carrying toxins into cancer cells/ 1 r Therapeutic human monoclonal antibodies are already in use as antirejection drugs for kidney transplantation, for treatment of rheumatoid arthritis, Crohn disease, and for some types of cancer/... 

This toxic protein is contained in caster seeds but does not pass into the oil. Similar phytotoxins occur in croton seeds (Crotin) jequirity seeds (Abrin) the bark of the locust tree, Robinia pseudo-acacia (Robin) and in the seeds of some leguminous plants (Phasin). The last is but weakly toxic. Ricin is responsible for the toxic effects on eating castor seeds 5 or 6 of these are fatal to a child, 20 to adults, and 3 or 4 seeds may cause violent gastroenteritis with nausea, headache, persistent vomiting, colic, sometimes bloody diarrhea, thirst, emaciation, and great debility. The symptoms usually do not set in until after several days. More severe intoxications cause small frequent pulse, cold sweat, icterus, and convulsions. Death occurs in 6 to 8 d, from the convulsions or from exhaustion. The fatality rate is about 6%. This low fatality rate is due to the destruction of the poison in the alimentary canal. The treatment would be evacuant and symptomatic. Usually, 3 to 10 d are required to complete recovery. 

As with some of the other chemicals discussed in this book, the possibility of using ricin as a drug, in particular for the treatment of cancer, has been explored. The possibility of attaching the part of the toxin that is lethal to cells, to antibodies, which would then target cancer cells, is being studied. 

It is well known that lipid peroxidation, DNA singlestrand breaks, and other forms of DNA damage occur in response to oxidative stress (Ames et al, 1982). Depletion of reduced glutathione also commonly precedes or accompanies lipid peroxidation and oxidative stress (Muldoon and Stohs, 1991 Omar et al, 1990). In an in vivo study, the effects of ricin administered orally on hepatic lipid peroxidation, nonprotein sulfhydryl content, and DNA singlestrand breaks were assessed in mice (Muldoon et al, 1992). The incidence of hepatic DNA damage increased 2.9-, 2.8-, and 2.4-fold relative to control values at 24, 36, and 48 h post-treatment with ricin, respectively. Hepatic nonprotein sulfhydryl concentration decreased significantly from 51 to 65% to control values at 24, 36, and 48 h post-treatment (Figures 25.2 and 25.3). 

There is no specific treatment for ricin or abrin. Therefore the only recommendation is to rid the body of the toxins as quickly as possible. Ricin and abrin poisoning is treated by giving victims the appropriate supportive medical care to... 

Houston, L.L. (1982). Protection of mice Irom ricin poisoning hy treatment with antibodies directed against ricin. J. Toxicol. Clin. Toxicol. 19 385-9. 

Christiansen SP, Becker BA, laizzo PA, et al. Extraocular muscle force generation after Ricin-mAb35 injection implications for strabismus treatment. JAAPOS 2003 7 1-6. 

Chemical Abstracts Service Registry Number CAS 1393-62-0. Abrin is a toxalbumin similar in structure, absorption, and mechanism of action to ricin but is found not in castor beans but rather in jequirity beans. No reports of its use as a battlefield or terrorist agent exist, but in mice it is 75 times more potent than ricin. No specific treatment is available. Both ricin and abrin are type 2 ribosomal inhibitory proteins (RIPs) the other potent toxins in this class are Eranthis hyemalis lectin (EHL) from winter aconite, modeccin and volkensin from African succulents, and viscumin from mistletoe. 

Though ricin can be deadly, most exposures result in uncomfortable but limited gastroenteritis and minimal systemic toxicity. Gastrointestinal decontamination should be considered, depending on the time of ingestion. Symptomatic and supportive measures are the mainstay of treatment. There is no specific antidote for this toxin. 

Treatment options are largely supportive. An assessment should first be made for airway patency and adequacy of breathing. Circulation may become affected as shock develops secondary to severe gastroenteritis. The following laboratory studies are recommended for all symptomatic patients computerized blood count, electrolytes, and coagulation studies (prothrobin time, activated partial thromboplastin time). In cases of uncertain or unknown exposure, there is an enzyme-linked immunosorption assay test available for the detection and verification of the presence of ricin... 

In addition to symptoms and physical findings, diagnostic clues for inhalational exposure may include bilateral pulmonary infiltrates on chest X-ray, arterial hypoxemia, neutrophilic leukocytosis and a bronchial aspirate rich in protein compared to plasma, characteristic of high permeability pulmonary edema (39). Unlike many biologic agents, ricin intoxication wonld progress despite treatment with antibiotics. 

Heating a 1% (w/v) solution of ricin to >85°C for 30 min results in complete inactivation as judged by toxicity in laboratory mice (Hunt et al., 1918). Dry heat of >100°C for 60 min in an ashing oven or steam autoclave treatment at >121 °C for 1 h reduces the activity of pure ricin by >99% (Wannemacher et al., 1989). Heat inactivation of impure toxin preparations (e.g., crude ricin plant extracts) may vary. Heat-denatured ricin can undergo limited refolding (<1%) to yield active toxin. Isolated RTA and RTB are more easily inactivated by heating than is the holotoxin (Olsnes et al., 1975 Taira et al., 1978). 

It has been observed that treatment of ricin or RTB with chloramine-T reduces toxic activity, although optimal conditions for complete inactivation are not established (Funatsu et al., 1970 Balint, 1974 Sandvig et al., 1976). 

Hewetson, J.F., Rivera, V.R., Creasia, D.A., Lemley, P.V., Rippy, M.K. and Poli, M.A. (1993) Protection of mice from inhaled ricin by vaccination with ricin or by passive treatment with heterologous antibody. Vaccine, 11, 743-746. 

Taira, E., Yoshizuak, N., Funatsu, G. and Funatsu, M. (1978) Effects of physical and chemical treatments on the biological activity of ricin D. Agric Biol Chem, 42, 1927-1932. 

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