Spontaneous poisoning by Ricinus communis leaves (Euphorbiaceae) in goats / Intoxicação espontânea por folhas de Ricinus communis (Euphorbiaceae) em caprinos

The aim of this study was to report the clinical and pathological aspects of an outbreak of poisoning by the ingestion of Ricinus communis leaves in a herd of goats at Pernambuco, northeastern Brazil. Within 3-5 hours after ingesting the sprouts and young shrubs of the plant, twenty Toggenburg female goats and two adults crossbred wethers presented acute neurological clinical signs, which were initially characterized by decreased locomotor activity that later evolved to severe ataxia, depression, incoordination and staggering gait. Four goat that died spontaneously were necropsied. Gross lesions were unspecific and consisted in focal areas of lungs edema, petechial hemorrhages in the epicardium and congestion and enlargement of liver. The contents of the rumen, reticulum and omasum were dry and contained leaves of the plant. Histologically there were no lesions in the CNS. In the liver, the main lesion consisted in cytoplasmic vacuolization and necrosis of hepatocytes. Eighteen goats recovered after a supportive therapy with activated charcoal, glycated isotonic solution, dexamethasone and vitamin B12. There is no specific therapy for poisoning by R. communis, however supportive and symptomatic treatments are recommended and should be based on the clinical signs.(AU)

O objetivo deste estudo foi relatar os aspectos clínicos e patológicos de um surto de intoxicação pelas folhas de Ricinus communis em um rebanho de caprinos em Pernambuco, Nordeste do Brasil. Três a cinco horas após a ingestão dos brotos e arbustos jovens da planta, vinte cabras da raça Toggenburg e dois machos mestiços apresentaram quadro clínico neurológico agudo caracterizado principalmente pela diminuição da atividade locomotora, grave ataxia, depressão, incoordenação e marcha cambaleante. Quatro caprinos morreram espontaneamente e foram necropsiados. Macroscopicamente, as lesões eram inespecíficas e consistiam em áreas focais de edema pulmonar, hemorragias petequiais epicárdicas e aumento do volume e congestão do fígado. Os conteúdos do rumem, retículo e omaso eram ressecados e continham folhas da planta. Histologicamente, não foram observadas lesões no SNC. No fígado, havia vacuolização citoplasmática e necrose de hepatócitos. Dezoito caprinos se recuperaram após receberem terapia de suporte com carvão ativado, soro glicosado, dexametasona e vitamina B12. Não existe terapêutica especifica para a intoxicação pelas folhas de R. Communis. Os tratamentos sintomáticos e de suporte são recomendados e devem basear-se nos sinais clínicos.(AU)

Cloning and chloroplast-targeted expression studies of insect-resistant gene with ricin fusion-gene under chloroplast transit peptide in cotton

Background: Transgenic plants inhabiting single Bt gene are prone to develop insect resistance and this resistance has been reported in case of some important yield-devastating insect larvae of commercial crops, such as cotton and rice. Therefore, it has become essential to adapt new strategies to overcome the problem of insect resistance and these new strategies should be sophisticated enough to target such resistant larvae in broad spectrum. Among these, plants may be transformed with Bt gene tagged with some fusion-protein gene that possesses lectin-binding capability to boost the binding sites for crystal protein gene within insect mid-gut in order to overcome any chances of insect tolerance against Bt toxin. Enhanced chloroplast-targeted Bt gene expression can also help in the reduction of insect resistance. Results: In the present investigation, a combined effect of both these strategies was successfully used in cotton (G. hirsutum). For this purpose, plant expression vector pKian-1 was created, after a series of cloning steps, carrying Cry1Ac gene ligated with chloroplast transit peptide towards N-terminal and Ricin B-Chain towards C-terminal, generating TP-Cry1Ac-RB construct. Conclusions: Efficacy of pKian-1 plasmid vector was confirmed by in-planta Agrobacterium-mediated leaf GUS assay in tobacco. Cotton (G. hirsutum) local variety MNH-786 was transformed with pKian-1 and the stable integration of TP-Cry1Ac-RB construct in putative transgenic plants was confirmed by PCR; while fusion-protein expression in cytosol as well as chloroplast was substantiated by Western blot analysis. Whereas, confocal microscopy of leaf-sections of transgenic plants exposed that hybrid-Bt protein was expressing inside chloroplasts.

Effect of interstitial chemotherapy with ricin temperature-responsive gel for anti-breast cancer and immune regulation in rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the effect of ricin temperature response gel on breast cancer and its regulatory effect on immune function in rats.</p><p><b>METHODS</b>Ricin was purified by chromatography and identified by immunoblotting. The rat subcutaneously transplanted breast cancer model was established. Forty model rats with a tumor diameter of about 3.0 cm were subjected to the study. They were randomized into four groups equally: the model group and three treated groups (blank gel, ricin, ricin-gel) were administered with blank gel, ricin, and ricin temperature response gel via percutaneous intratumor injection, respectively. The tumor was isolated 10 days later for the estimation of tumor inhibition rate (TIR) by weighing, pathologic examination, and detection of tumor apoptosis-associated genes bcl-2 and bax with semiquantitative RT-PCR. Also, peripheral blood was obtained to test T-lymphocyte subsets, the killing function of lymphocytes, and the contents of tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2). The outcomes were compared between groups.</p><p><b>RESULTS</b>The TIR in the ricin-gel group was 61.8%, with the pathologic examination showing extensive tumor tissue necrosis. Compared with the model group, after ricin temperature response gel treatment, bcl-2 expression was down-regulated, bax expression was up-regulated, CD4+ lymphocytes and CD4+/CD8+ ratio in peripheral blood were increased, the killing function of lymphocytes was enhanced, and the contents of TNF-α and IL-2 were elevated (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>Intratumor injection of ricin temperature-responsive gel showed significant antitumor effect on breast cancer and could enhance the immune function in the tumor-bearing rat.</p>

Simultaneous allergen inactivation and detoxification of castor bean cake by treatment with calcium compounds

Ricinus communis L. is of great economic importance due to the oil extracted from its seeds. Castor oil has been used for pharmaceutical and industrial applications, as a lubricant or coating agent, as a component of plastic products, as a fungicide or in the synthesis of biodiesel fuels. After oil extraction, a castor cake with a large amount of protein is obtained. However, this by-product cannot be used as animal feed due to the presence of toxic (ricin) and allergenic (2S albumin) proteins. Here, we propose two processes for detoxification and allergen inactivation of the castor cake. In addition, we establish a biological test to detect ricin and validate these detoxification processes. In this test, Vero cells were treated with ricin, and cell death was assessed by cell counting and measurement of lactate dehydrogenase activity. The limit of detection of the Vero cell assay was 10 ng/mL using a concentration of 1.6 x 10(5) cells/well. Solid-state fermentation (SSF) and treatment with calcium compounds were used as cake detoxification processes. For SSF, Aspergillus niger was grown using a castor cake as a substrate, and this cake was analyzed after 24, 48, 72, and 96 h of SSF. Ricin was eliminated after 24 h of SSF treatment. The cake was treated with 4 or 8% Ca(OH)2 or CaO, and both the toxicity and the allergenic properties were entirely abolished. A by-product free of toxicity and allergens was obtained.

Avaliação de cultivares de mamona em três ambientes, no estado do Tocantins, safra 2007/2008 / Avaluation of castor bean cultivars in three environments in the state of Tocantins, agricultural year 2007/2008

A mamona (Ricinus communis L.) surge como fonte alternativa de energia na produção de biodiesel, tornando a cultura da mamoneira importante potencial econômico e estratégico ao País. Com o objetivo de avaliar o comportamento produtivo das cultivares de mamonas, foram realizados ensaios de competição em três locais no Estado do Tocantins. O experimento foi instalado em blocos casualizados com três repetições. Cada parcela experimental, foi constituída por duas linhas de 6 metros de comprimento por 1,5 metros entre linhas, totalizando 18 metros quadrados por parcela, utilizando as cultivares (IAC 226, Guarani, Nordestina e Paraguaçu), semeadas em Gurupi, Natividade e Formoso do Araguaia As características avaliadas foram altura da planta, altura dos cachos, número cachos por planta, produtividade de cachos por hectare, peso de sementes por hectare e diâmetro de caule. A metodologia utilizada proporcionou informações, que permitiram conhecimento tanto das cultivares avaliadas, quanto aos ambientes estudados. Utilizou-se o teste de Tukey para as médias da produção de sementes (kg.ha-1), foram detectadas diferenças significativas entre as cultivares em todos os ambientes e na média geral, porém os resultados indicam a superioridade de alguns materiais. Os ensaios apresentaram um comportamento diferencial das cultivares nos ambientes diferentes, sendo realizados os desdobramentos. Analisou-se a produtividade em kg.ha-1 nos três ambientes. Em Gurupi a média de produtividade foi superior aos demais ambientes. A cultivar Guarani a que mais se destacou e revelando um comportamento potencialmente promissor em todos os ambientes estudados.

The castor bean (Ricinus communis L.) has emerged as an alternative source of energy in biodiesel production, making the cultivation of the castor and important potential economic and strategic to the country In order to evaluate. The production of the castor bean cultivars, was avaluated at Tocantins. The experiment was conducted in blocks with three replications. Each experimental plot consisted of two rows of six meters long and 1.5 meters between two lines, totaling 18 square meters per plot, using cultivars (IAC 226, Guarani, and Northeastern Paraguaçu), seeded in Gurupi Nativity and Formoso do Araguaia. The traits evaluated were plant height, height of the clusters, many clusters per plant, yield of bunches per hectare, seed weight per hectare and stem diameter. The methodology provided information that allowed knowledge of the cultivars and environmental variations. We used the Tukey test for means of production of seed (kg ha-1), significant differences between cultivars in all environmental and in general average, but the results indicate the superiority of some materials. The tests showed a differential behavior of the cultivars in distinct environments and being performed developments. We analyzes the yield in (kg ha-1) in the three environments. In Gurupi the average yield was higher than the other environments. The Guarani cultivar that stood out and revealing to be a potentially promising behavior in all environmental studied.

case of castor bean poisoning

Castor beans, sometimes used in traditional therapies, contain ricin one of the most toxic substances known. It may cause an acute and potentially fatal gastroenteritis in addition to neurological and ophthalmological lesions. Poisoning may also lead to delayed visceral damages; however, the latter is quite rare. The toxicity is dose related and depends on the amount of castor beans ingested. There is no specific treatment and symptomatic management to reduce the load of the toxin needs to be initiated quickly and early when a case of poisoning is suspected so that serious complications will be avoided. Increasing the awareness of the population to the dangers of ricin would be a way to avoid the utilisation of castor seeds in traditional therapies. Here we are reporting a case of mild poisoning after ingestion of a single castor bean. The patient, who presented at Nizwa Hospital, Oman, fortunately recovered completely as the ingested dose was quite small

Study on lysosomes degradation of ricin A chain / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study lysosomes involvement in the degradation of ricin A chain.</p><p><b>METHODS</b>A lysosome-targeted singal KFERQ was added to the C terminus of rRTA by DNA recombinant technology. A pKK223.3 expression system in E. coli was used to produce recombinant ricine A chain (rRTA) and rRTA-KFERQ. Recombinant proteins were purified by affinity chromatography using Blue-Sepharose 6B. The cytotoxicity of recombinant proteins was measured by the MTT method.</p><p><b>RESULTS</b>Recombinant RTA-KFERQ was 49.87%, 54.18% and 88.68% less cytotoxic than RTA itself on the three cell lines HEPG2, Hela and A549, respectively.</p><p><b>CONCLUSION</b>Lysosomes can degrade, but not completely inactivate RTA in different cells, suggesting cells may have other degradation pathways for RTA.</p>

Purification and anti-cancer activity of ricin / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To extract and purify ricin from castor beans and to evaluate its anti-cancer activity.</p><p><b>METHODS</b>Ricin was purified from castor beans according the modified method of Nicolson and Blaustin. The lectins were extracted in 0.01 mol/L phosphate buffered saline and isolated in the 40% to 80% fraction of ammonium sulfate precipitation. The dialyzed fractionated preparation was applied with a Sepharose 4B column. The lectins were eluted with a linear lactose gradient (0.01 mol/L approximately 0.5 mol/L). Ricin was separated from the ricinus agglutinin by gel filtration on a Sephadex G-100. MTT was applied to analyze the cytotoxicity with different dosage of ricin in different cancer cell lines.</p><p><b>RESULTS</b>There was no difference between the killing effect of normal cells and that of colon cancer cells by using the high dosage of ricin (5 x 10(-8) mol/L approximately 5 x 10(-10) mol/L). However, the cytotoxicity was significant different in those cells with the low dosage of ricin (5 x 10(-11) mol/L approximately 5 x 10(-13) mol/L). Meanwhile ricin had the similar cytotoxicity to leukemia cell K562 and colon cancer cell SW480.</p><p><b>CONCLUSION</b>Ricin is able to kill tumor cells selectively at low concentration, but the selectivity does not appear at high concentrations.</p>

Construction and expression of ricin A chain and green fluorescent protein fusion gene in E. coli / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the expression and purification of a fusion protein of ricin A chain (RTA) and green fluorescent protein (GFP).</p><p><b>METHODS</b>The DNA sequence encoding ricin A chain was inserted into pEGFPC1 first to make the template sequence of the fusion protein. The fusion gene was amplified from the plasmid pEGFP-RTA by PCR, and directly subcloned into T vector. The fusion gene then was cloned into expression vector pET-28a(+), and the sequence was confirmed by sequencing. Expression was induced by IPTG in E. coli BL21(DE3). The fusion protein was purified by metal chelated affinity chromatography. The cytotoxicity of fusion protein was analyzed by the MTT assay in HepG2 and Hela cells.</p><p><b>RESULTS</b>The fusion protein of ricin A chain and GFP could be produced in E. coli transformed with the expression plasmid of pET-28a(+)-GFP-RTA. The molecular weight of the recombinant protein was measured by SDS-PAGE. The fusion protein showed a green fluorescence and had a similar cytotoxicity of RTA.</p><p><b>CONCLUSION</b>A recombinant fusion protein of RTA and GFP expressed in E. coli is possessed of similar biological activity of individual GFP and RTA, which could be used in study of the intracellular trafficking and translocation of RTA.</p>

Histologic Analysis of the Myotoxic Change by Bupivacaine and Ricin mAb 35 on Extraocular Muscle in Rabbits

PURPOSE: To analyze the acute histologic change of extraocular muscles (EOM) induced by injection of bupivacaine or Ricin mAb 35. METHODS: The superior rectus and inferior rectus of white rabbits were injected with either bupivacaine (0.4 mg in 0.3ml) or Ricin mAb 35 (0.2 micro gram/kg in 0.3 ml). One, two, and four weeks after injection, the rectus muscles were harvested and the post-injection changes were histologically analyzed. RESULTS: Both the orbital and the global layers of EOM showed myotoxic changes induced by bupivacaine and Ricin mAb 35. However, the inflammation and destruction of myofiber by bupivacaine injection were localized to the injection site, whereas changes induced by Ricin mAb 35 were diffuse. Regenerating myofibers with a central nucleus were found at one week after myotoxin injection. Four weeks after injection, the acute changes induced by these two toxins were much recovered with prominent myofiber regeneration. Bupivacaine-induced myotoxic change was more prominent in the global layer in contrast to the more prominent damage in the orbital layer induced by Ricin mAb 35. CONCLUSIONS: We found that EOM have a superb ability to recover from the acute injury induced by bupivacaine or Ricin mAb 35 and that the two myotoxins cause unique damage including the predilection of muscle layers and the duration for which the damage persisted. Further investigation into the functional change during recovery from the myotoxin-induced injury of EOM is needed.

Application of ricin-immunotoxin mediated T cell depletion to allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

This study was aimed to investigate the clinical outcome of ricin-immunotoxin mediated T cell partially depleted HLA/MLC mismatched allogeneic hematopoietic stem cell transplantation. 13 patients with hematological malignancies were treated by ricin-immunotoxin mediated T cell partially depleted allogeneic hematopoietic stem cell transplantations from HLA/MLC mismatched donors, including 6 cases of CML in CP(1), 1 case of ALL in CR(1), 1 case of ALL in CR(2), 1 case of ALL in relapse, 2 cases of AML in CR(1), 1 case of AML in CR(2), 1 case of MDS-RAEBT-AML (M(4)) in CR(1). The results showed that 8 cases were engrafted successfully, 2 cases of them developed grade II acute GVHD and 2 cases developed grade III-IV acute GVHD. Within following-up of 8 - 90 months, 2 patients who experienced grade III-IV acute GVHD died early after transplantation; 1 patient died of late onset of infection; the other 5 patients survived free from diseases. After failure at first infusion, 4 patients were given reinfusion of peripheral blood hematopoietic stem cells from the same donor. 3 out of 4 cases failed to engraft and only one patient got engraftment but died of related complications of transplantation. One patient was performed a second transplantation from a syngeneic donor and survive free of disease until now. In conclusion, T cell partially depleted HLA/MLC mismatched allogeneic hematopoietic stem cell transplantation by ricin-immunotoxin decreases the occurrence of severe acute GVHD but with high risk of rejection, which clinical outcome still needs further evaluation.

Effect of modified ricin on the reduction of hepatotoxicity in mice / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the significance of ricin (RT) with chemical nidification to reduce the hepatotoxicity in mice and its anticancer effect.</p><p><b>METHODS</b>Mice were exposed to RT and RT-PDP [ricin chemically modified by N-succinimidyl 3-(2-pyridyldithio)-propionate, (SPDP)] respectively, and their serum activity of glutathione-S-transferase (GST) and liver glutathione (GSH) content were determined. The ultramicro-structure under electron microscope was also observed.</p><p><b>RESULTS</b>The GST activity increased with doses, and the increase in ricin group was higher than that in RT-PDP group; the activities of GST in RT group at 12.5, 15.0 micro g/kg [(93.65 +/- 12.30), (153.71 +/- 26.64) IU/L respectively] were higher than those in RT-PDP group [(62.97 +/- 11.22), (78.20 +/- 15.71) IU/L] (P < 0.05). The contents of GSH were decreased with doses; but the contents of GSH in RT-PDP group at 2.5, 5.0, 7.5, 10.0, 15.0 micro g/kg [(6.34 +/- 1.43), (4.14 +/- 1.82), (3.54 +/- 0.64), (2.73 +/- 1.82), (1.82 +/- 0.62) micro mol/L respectively] were still higher than those in RT group [(3.53 +/- 0.95), (2.12 +/- 0.54), (1.82 +/- 0.71), (1.52 +/- 0.34), (0.81 +/- 0.36) micro mol/L] (P < 0.01). Electron microscopic examination showed that the injury of liver cells in RT group was more severe than that in RT-PDP group.</p><p><b>CONCLUSION</b>The hepatotoxicity of ricin in mice may be reduced by chemical modification.</p>

Biopolímero da mamona na reconstrução de falhas ósseas após ressecção de tumores no esqueleto apendicular / Clinical application of pre molded mamona polymer for the reconstruction of bone defescts after resectiion of tumores of the skeleton

O estudo teve por objetivo avaliar os resultados da utilização do polímero da mamona em forma de blocos pré-fabricados, como biomaterial para utilização nas reconstruções de grandes falhas ósseas decorrentes da ressecção de tumores benignos agressivos e tumores malignos. foram avaliados 20 pacientes entre 2000 e 2002 com tempo de seguimentode 26 e 147 semanas (78,3 ñ35,1 semanas). As falhas ósseas foram reconstruídas com blocos pré-fabricados de polímero de mamona, tendo sido adaptados e fixados ao leito recptor de acordo com a margem e o tipo de ressecção. Foi utilizado o método de avaliação clínica proposto por Mankin et al. Tendo-se obtido 7 (35por cento) de resultado excelente, 4 (20por cento) bons, 4(20por cento) regulares e 5 (25por cento) de falhas. O biopolímero apresentou como vantagens: disponibilidade; baixo custo; ausência de riscos de transmissão de doenças; ser biocompativel e osteointegrável. O polimero da mamona foi considerado uma alternativa viável para reconstrução de falhas ósseas pós ressecção de tumores benignos agressivos e maliginos

Utilizaçäo dos implantes de polietileno-mrfpor, poliuretana de mamoma e matriz óssea bovina em defeitos ósseos maxilares: análise histológica e histométrica em macacos / Experimental evaluation of the three different implants: polyetylene, poliuretane and bovine bone matrix, implanted in maxillary bone defects: histologic and histomorphometric study in monkeys

O presente estudo teve como finalidade avaliar o processo de reparo ósseo em defeitos cirúrgicos realizados na parede anterior do seio maxilar após osteotomia e colocaçäo de implantes de polietileno poroso de alta densidade - Medpor, poliuretana de mamona (Ricinus communis) e matriz óssea desmineralizada bovina. Foram empregados 8 macacos pregos (Cebus apella). As análises foram feitas após 145 dias de implantaçäo através de avaliaçöes histológicas e histométricas utilizando método de microscopia óptica computadorizada - Imagelab 98. Os resultados mostraram que o reparo ósseo se estabeleceu em 77,24 por cento da superfície de contato com a matriz óssea bovina, 41,31 por cento com o Medpor e 28,24 por cento do polímero de mamona. Houve prevalência de neoformaçäo conjuntiva (58,5 por cento) no grupo sem implantaçöes. Como conclusöes finais podemos afirmar que o melhor comportamento histomorfológico foi da matriz óssea bovina, seguida do polietileno poroso de alta densidade - Medpor e da poliuretana de mamona (Ricinus communis), o qual respondeu com intensa fibrose e moderado infiltrado inflamatório crônico tardio

Imunidade cruzada pelas sementes de Abrus precatorius e Ricinus communis em bovinos / Crossimmunity by the seeds of Abrus precatorius and Ricinus communis in cattle

Cinco bovinos imunizados contra a ação tóxica das sementes de Abrus precatorius L. ("tento", "jiquiriti") não adoeceram ou somente levemente pela administração das sementes de Ricinus communis L. ("mamona"), em doses que em bovinos que antes nunca ingeriram sementes de A. precatorius ou R. communis, causaram intoxicação de intensidade de grau moderado a acentuado ou até a morte. Um sexto bovino, que não ficou bem imunizado contra a ação tóxica das sementes de A. precatorius, adoeceu em grau acentuado pela administração de dose elevada das sementes de R. communis. Já dos cinco bovinos imunizados contra a ação tóxica das sementes de R. communis quatro adoeceram em grau acentuado, oquinto em grau moderado, pela administração das sementes de A. precatorias em doses que em bovinos que antes nunca ingeriram sementes de R. communis ou A. precatorius causaram intoxicação de intensidade leve a acentuada. Estes resultados permitem concluir que bovinos imunizados contra a ação tóxica das sementes de A. precatorius são resistentes à ação tóxica das sementes de R. communis, mas que o contrário não ocorre, isto é, bovinos imunizados contra a ação tóxica das sementes de R. communis, não se mostraram protegidos contra a intoxicação por A. precatorius. Estudos anteriores por outros autores mostraram que as toxalbuminas de A. precatorius e R. communis, respectivamente abrina e ricina, são diferentes do ponto de vista antigênico. Uma explicação para a divergência desses resultados com os nossos poderia estar no fato de que no presente estudo foram usados poligástricos que receberam as sementes por via oral, enquanto que nos estudos anteriores foram usados monogástricos em que as sementes ou as toxinas foram aplicadas por via parenteral. A administração de folhas frescas ou do pericarpo do fruto de R. communis a bovinos imunizados contra a ação das sementes desta planta tiveram o mesmo efeito tóxico que em animais não imunizados, demonstrando que a imunidade conferida pela ricina não inibe a ação da ricinina, o principio tóxico das folhas e do pericarpo

Avaliaçäo da toxicidade sistêmica da poliuretana derivada de óleo de mamona: resultados preliminares / Evaluation of systemic toxicity of polyurethane derivade castor-oil plant: preliminary results

Seguindo normatizações internacionais (ASTM), a avaliação toxicológica de um material polimérico derivado de óleo de mamona está sendo feita através da injeção sistêmica em camundongos albinos. Posteriormente, será feita a averiguação histopatológica de rins, fígado, baço e pulmões. Os sinais clínicos apresentados pelos animais após a injeção não revelaram aspectos de toxicidade

Abstract - The toxicological evaluation of a polymeric material from castor oil is being carried out by systemic injection in albino mice and by a subsequent histopathological analysis of their kidneys, liver, spleen and lungs. The animais have not developed clinicai signs of toxicity after the injection. Histopathological analysis of their organs were not concluded yet

Role of antioxidant enzyme defence in sparing rat hepatocytes from toxicity of ricin at low dose.

Ricin, a glycoprotein from castor oil seeds, is specifically toxic to Kupffer cells and at low doses it leaves parenchymal cells comparatively unaffected. At a dose of approximately 1.5 microgram/100 g body weight, ricin significantly increases the hepatic antioxidant enzyme system in rats within 24 hr. Superoxide dismutase, catalase and glutathione peroxidase show an increase in liver tissue levels of 19-24%. However, hepatic lipid peroxidation is elevated by about 34% and non-protein sulphydryl is reduced by 26%. The enhanced levels of antioxidant enzymes appear to protect the hepatocytes from the toxin. The observed elevation of hepatic thiobarbituric acid-reactive substances appears to originate mainly from the damaged Kupffer cells.

Potentiation of ricin cytotoxicity by liposomal monensin under in vitro and in vivo conditions.

Effect of monensin, intercalated in liposomes on the cytotoxicities of ricin, Pseudomonas exotoxin A and diphtheria toxin in phagocytic and non-phagocytic cells as well as in mice has been studied. Intercalation does not disturb the integrity of the liposomal bilayer and substantially enhances the cytotoxicities of ricin and Pseudomonas exotoxin A in both phagocytic and non-phagocytic cells while it has no effect on diphtheria toxin. The observed effect is highly dependent on the liposomal lipid composition as well as cell types. The potentiating ability of monensin in neutral vesicle is 2.2-fold higher than in negatively charged vesicles in non-phagocytic cells while no difference was observed in phagocytic cells. Incorporation of stearylamine in liposomes reduces the potentiating effect of monensin. Liposomal monensin has also been found to enhance the cytotoxicity of ricin in mouse in vivo in a dose-dependent manner and is maximal when ricin is injected within 60 min of monensin injection. Liposomal monensin remains in circulation for 2 hr while free monensin remains only for 15 min. Tissue distribution studies reveal that liposomal monensin is present mainly in the liver and spleen which are also the major sites for ricin accumulation. Thus liposome is found to be an effective delivery vehicle for monensin to potentiate the cytotoxicity of immunotoxins or hormonotoxins and could prove useful for selective elimination of cancer cells.