Deoxynivalenol (DON) contamination of grain destined for animal feeds is a major toxicological risk to monogastrics and is suspected of restricting productivity in ruminants. Whereas bacterial additives have been developed that can detoxify DON in the rumen and lower intestine, there are currently no commercial inoculants able to perform this task in crimped grain (CG) silage, a regionally important method of moist grain preservation based on homo- and heterofermentative lactic acid bacteria or chemical additives. Determining whether this ensiling process alongside the action of detoxifying bacteria has the potential to remove DON in CG prior to ingestion, was explored in mini-silo ensiling experiments. CG was heat treated (100 °C, 60 min) or ensiled fresh in triplicate 50 g silos, spiked with 5 mg/kg DON and inoculated with lactic acid bacteria derived from wild birds, natural epiphytic inoculants and commercially sourced silage additives (21 d). DON recovery was only significantly reduced (31.2 ± 14.4% recovery, p < 0.001, n= 30) by heat treatment, as determined by IAC-RP-HPLC-UV. Bacterial assemblage analysis by 16S rRNA PCR-DGGE-SEQ identified Weissella cibaria, Pantoea agglomerans, Bacillus subtilis, B. licheniformis and Hafnia alvei as candidate detoxification agents, of which W. cibaria and H. alvei decreased DON recovery in vitro (11.3 and 6.2% recovery respectively, p < 0.05, n = 18), which translated to inoculated W. cibaria yielding a decrease in DON recovery (67.2± 14.4%, 28 d) in naturally contaminated crimped wheat (13.5 ± 1.0 mg/kg, 35-40% moisture, p < 0.05, n =15). As W. cibaria is a lactic acid bacteria already associated with fermented CG by default it has promise as a novel DON detoxification agent in CG silage. DON is however just one of many hepatotoxic co-contaminants. Retrorsine, a DNA-crosslinking pyrrolizidine alkaloid derived from Ragwort (Senecio sp.) was investigated for interactive toxicity with DON in an in vitro co-exposure experiment. HepG2 cells were exposed to Log10 multifactorial binary exposures for 48 h followed by a suite of assays to elucidate mechanisms of interactive cytotoxicity, genotoxicity and modulation of the proteome. Retrorsine was tentatively confirmed to form DNA/protein crosslinks in the comet, micronucleus and crosslinking assays, whilst DON was found to potently induce cytotoxicity and apoptosis. Co-exposure yielded a complex toxicity response, with low doses yielding antagonistic effects and high doses trending towards additive effects, although DON dose was generally the principle component. The difficulties associated with undertaking an interactive toxicity study where both toxins have multiple metabolic and cellular targets are highlighted.

Objective: To report a case of deep vein thrombosis (DVT) with symptomatic pulmonary embolism (PE) possibly associated with the use of coltsfoot, kava, or blue vervain. Case Summary: A 27-year-old white male presented with leg pain and swelling, tachycardia, and pleuritic chest pain. He had no significant medical history. A medication history revealed extensive herbal medication use including: coltsfoot, passionflower, red poppy flower petals, wild lettuce, blue lily flowers, wild dagga flowers, Diviners Three Burning Blend® (comprised of salvia divinorum, blue lily, and wild dagga), kavakava, St. John's Wort, blue vervain, and Dreamer's Blend® (comprised of Calea zacatechichi, vervain, Entada rheedii, wild lettuce, and Eschscholzia californica). Lower extremity Doppler ultrasound and computed topography (CT) of the chest revealed DVT and PE. A hypercoagulable work-up was negative. The patient was treated with enoxaparin and warfarin and was discharged home. Discussion: While no distinct agent can be identified as a sole cause of this venous thromboembolic event, coltsfoot could potentially affect coagulation through its effect on vascular endothelial cells as they regulate nitric oxide. Nitric oxide is a known mediator of platelet activity and coagulation, particularly in the pulmonary vasculature. Kava and vervain have estrogenic properties. Conclusions: Of the medications consumed by this self-proclaimed "herbalist," coltsfoot is a potential cause of venous thromboembolic disease (VTE).

Made available in DSpace on 2015-05-14T12:59:54Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 7265191 bytes, checksum: 432cedb6fda0226806b02fd0634dfff5 (MD5) Previous issue date: 2013-08-12 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The poisonous plants to livestock research has been restricted only the identification of poison species, epidemiology and clinical signs. But the active principle of toxic plants are little known and its knowledge its very important to develop preventive methods to poisoning which are responsible by countless cattle deaths. This work aimed the contribution to knowledge of active principle these plants, Crotalaria vitellina Ker Gawl (Fabaceae) e Ipomoea philomega (Vell.) House (Convolvulaceae). This work aimed the contribution to knowledge of active principle these plants, Crotalaria and Ipomoea were submitted to phytochemical study for the isolation of its chemical constituents by cromatographic methods followed by its identification through spectroscopic techniques such as Infrared (IR), one and two-dimentional Nuclear Magnetic Resonance (NMR) of 1H and 13C, and Mass Spectrometry (MS) besides literature data. The phytochemical study of C. vitellina resulted on the isolation of the pyrrolizidine alkaloid (type otonecine) named crotavitelin (Cv-1), and were obtained from the crude extract of its fruits, described by first time in the literature. This substance was subjected to acute toxicological evaluation according to OECD Guide 423 (Guideline for Testing of Chemicals), in mice (males and females) orally exposed to 50 and 300 mg/Kg doses and showed a low toxicity on the parameters evaluated. However, histopatologic studies should be performed to investigate the possible toxic effects in celular and tissue levels. Ipomoea philomega was submitted also to phytochemical studies and were isolated eight compounds from the dicloromethane phase of the ethanolic crude extract of the leaves: lanosterol (Ip-1), caffeic acid (Ip-2), ethyl p-coumarate (Ip-3), lupeol (Ip-4), ethyl caffeate (Ip-5), umbelliferone (Ip-6), scopoletin (Ip-7), and the 1,2-benzopirone (Ip-8), has been described for first time in I. philomega. / A pesquisa sobre plantas tóxicas para animais têm-se limitado principalmente à identificação das espécies, bem como à sua epidemiologia, patologia e sinais clínicos. Sendo, no entanto, pouco conhecidos os seus princípios ativos, cujo conhecimento é de grande importância no desenvolvimento de métodos preventivos da intoxicação, responsáveis por inúmeras mortes de animais e, consequentemente, perdas econômicas. Visando contribuir para o conhecimento dos princípios ativos dessas plantas, as espécies Crotalaria vitellina Ker Gawl (Fabaceae) e Ipomoea philomega (Vell.) House (Convolvulaceae) foram submetidas a um estudo fitoquímico para isolamento de seus constituintes químicos por métodos cromatográficos, seguidos de identificação através de métodos espectroscópicos tais como Infravermelho (IV), Ressonância Magnética Nuclear (RMN) de 1H e 13C uni e bi-dimensionais e Espectroscopia de Massas (EM) juntamente com a comparação com dados da literatura. O estudo fitoquimico do extrato etanólico bruto dos frutos e folhas de C. vitellina resultou no isolamento de um alcalóide pirrolizidínico do tipo otonecina, descrito pela primeira vez na literatura, nomeado crotavitelina (Cv-1). Essa substância foi submetida avaliação da toxicidade pré-clínica aguda, de acordo com o Guia da OECD-423 (Guideline for Testing of Chemicals), em camundongos (machos e fêmeas) nas doses de 50 e 300 mg/Kg e apresentou baixa toxicidade nos parâmetros avaliados. Entretanto, estudos histopatológicos, especialmente em nível de tecido hepático, devem ser realizados para a investigação de possíveis efeitos tóxicos em nível celular e tecidual. Ipomoea philomega, Convolvulaceae, igualmente submetida a estudo fitoquímico do extrato etanólico bruto das suas folhas possibilitou o isolamento de oito substâncias da fase diclorometano: lanosterol (Ip-1), ácido cafeico (Ip-2), p-cumarato de etila (Ip-3), lupeol (Ip-4), cafeato de etila (Ip-5), umbeliferona (Ip-6), escopoletina (Ip-7) e a 1,2- benzopirona (Ip-8), descritas pela primeira vez para I. philomega.