€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF ENVIRONMENTAL PATHOLOGY, TOXICOLOGY AND ONCOLOGY***** Keeler RF Baker DC Panter KE Concentration of galegine in Verbesina encelioides and Galega oficinalis and the toxic and pathologic effects induced by the plants. In: J Environ Pathol Toxicol Oncol (1992 Mar-Apr) 11(2):11-7 ISSN: 0731-8898 Verbesina encelioides administered to sheep by gavage induced clinical signs of toxicity and pathologic lesions identical to those induced by Galega officinalis. Sheep had compromised respiratory function with shallow, rapid respiration and frothy exudate from the nares. Affected animals necropsied at time of death presented with hydrothorax with as much as 2 to 3 L of straw-colored thoracic fluid with fibrin tags and congestion and edema of the lungs. The trachea and lung airways contained frothy material with fibrin strands. In some cases, subendocardial hemorrhage of the left ventricle was present. Galegine, a guanidine compound believed to be responsible for these effects, was found at an average concentration of about 0.46% in Galega and at 0.08% in the Verbesina collection that induced toxicosis. While G. officinalis is a known poisonous plant, its very limited distribution in the U.S. causes it to be of minor importance. V. encelioides, however, is widely distributed in the U.S. and presents a potential hazard for grazing livestock. Verbesina may have been responsible for past livestock deaths in the U.S., and thus should be classified as a poisonous plant. Registry Numbers: 543-83-9 (galegine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF MEDICINAL CHEMISTRY***** Delle Monache G Botta B Delle Monache F Espinal R De Bonnevaux SC De Luca C Botta M Corelli F Carmignani M Novel hypotensive agents from Verbesina caracasana. 2. Synthesis and pharmacology of caracasanamide. In: J Med Chem (1993 Oct 1) 36(20):2956-63 ISSN: 0022-2623 Caracasanamide, one of the hypotensive agents isolated from Verbesina caracasana, is a mixture of (Z)-1a and (E)-1b forms of 1-[(3,4- dimethoxycinnamoyl)amino]-4- [(3-methyl-2-butenyl)-guanidino]butane. The structure of (E)-caracasanamide (1b) was confirmed by high- yielding synthesis starting from N,N'-bis(tert-butoxycarbonyl)-S- methylisothiourea. The water-soluble Z-form of 1a, assayed by i.v. route in anesthetized rats at doses ranging from 50 to 1600 micrograms/kg body weight, was found to decrease blood pressure, to increase cardiac inotropism, respiratory frequency, and tidal volume, and to induce a very slight and not significant tachycardia. Higher doses determined respiratory depression and, in some cases, consequent cardiac arrest. The compound was shown to affect cardiovascular function by acting at the vascular level in inducing arterial vasodilation, by determining sympathetic hypotone through central neurogenic mechanisms, and by interacting with the cardiac beta 1-adrenoreceptors. The respiratory effects were independent of the cardiovascular ones. In lowering blood pressure, the compound was more potent than guanethidine and not less potent than reserpine and papaverine. (Z)-Caracasanamide may therefore be useful in the treatment of arterial hypertension of moderate degree. Registry Numbers: 146269-39-8 (caracasanamide) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****VETERINARY AND HUMAN TOXICOLOGY***** Lopez TA Campero CM Chayer R Cosentino B Caracino M Experimental toxicity of verbesina encelioides in sheep and isolation of galegine. In: Vet Hum Toxicol (1996 Dec) 38(6):417-9 ISSN: 0145-6296 Verbesina encelioides is a widely distributed weed in Argentina. Although it has been suspected as poisonous, there seem to be no previous reports of its toxicity in this country. Its biological activity was evaluated through an experiment in sheep. Four 5-y-old sheep, averaging 33 kg in body weight, were given a single dose of 1.0, 3.2, 5.0 or 6.3 g of dried plant material (17.9% dry matter)/kg body weight orally in a water suspension. Forty-eight hours later, the animals given 5.0 g or 6.3 g showed dullness and lack of appetite. The higher dosed sheep became recumbent a few hours later and died 60 h after dosing without showing further signs. The other animals showed no signs. Necropsy of the dead sheep showed severe lesions in different organs: liver, kidneys, lungs, lymph nodes and digestive tract. Hydrothorax was also observed. The animal receiving 5.0 g/kg was sacrificed after 72 h to determine the degree of recovery or lesions. Microscopically, severe glomerulonephrosis and congestion in the liver, with cellular degeneration and fatty changes were observed. Additionally, hemorrhagic lymph nodes, and hemorrhagic and edematous lungs were noted. No gross nor microscopic lesions were found in the sheep receiving 5.0 g/kg. Mice injected ip with the chromatographic extract died in less than 15 min. Galegine was identified in the plant material. The minimum toxic dose of 5-6 g/kg indicates a high toxicity when compared to other poisonous plants of the southeastern area of Buenos Aires province, Argentina. Registry Numbers: 543-83-9 (galegine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Keeler RF Johnson AE Stuart LD Evans JO Toxicosis from and possible adaptation to Galega officinalis in sheep and the relationship to Verbesina encelioides toxicosis. In: Vet Hum Toxicol (1986 Aug) 28(4):309-15 ISSN: 0145-6296 Galega officinalis L (goatsrue), a plant introduced from Europe and found in abundance in northern Utah, was tested for toxicity in ewes (Ovis aries). Clinical signs of poisoning induced by doses as small as 0.8 g of dried plant/kg body weight/day included dyspnea, anoxia, and foaming nasal discharge. Pathologic signs in animals that died following overdose of the plant included severe hydrothorax, generalized lung congestion, foamy exudate in bronchioles and trachea, epicardial and endocardial petechiation, and pericardial effusion in severely affected ewes. Microscopic lesions included a severe diffuse alveolar and interlobular edema. No significant alterations in blood constituents were observed in treated animals. Ewes administered the plant on several consecutive days developed an apparent adaptation to the toxin of the plant and were thereby able subsequently to tolerate levels 5-10 times the pre-treatment lethal dose with no discernible adverse clinical or pathological effects. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€