The Experts below are selected from a list of 78 Experts worldwide ranked by ideXlab platform
Stephen T. Lee - One of the best experts on this subject based on the ideXlab platform.
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microsomal activation and sh sy5y cell toxicity studies of Tremetone and 6 hydroxyTremetone isolated from rayless goldenrod isocoma pluriflora and white snakeroot agertina altissima respectively
Toxicon: X, 2020Co-Authors: Benedict T. Green, Stephen T. Lee, Zane T Davis, Kevin D WelchAbstract:Abstract This research compared the cytotoxic actions of the benzofuran ketone, Tremetone in B16 murine melanoma cells to SH-SY5Y human neuroblastoma cells with an MTT assay. Tremetone was not cytotoxic in B16 cells. In SH-SY5Y cells, concentration-dependent Tremetone cytotoxicity occurred without microsomal activation. No cytotoxicity was observed with 6-hydroxyTremetone. This suggests that SH-SY5Y cells are a better model for the cytotoxic actions of Tremetone and that Tremetone is toxic without microsomal activation.
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white snakeroot poisoning in goats variations in toxicity with different plant chemotypes
Research in Veterinary Science, 2016Co-Authors: T.z. Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Tim J. Evans, James A. Pfister, M G Collett, Daniel Grum, S BuckAbstract:Tremetone and possibly other benzofuran ketones are believed to be the toxic compounds in white snakeroot. However, disease has not been reproduced with purified toxins and the concentrations of the benzofuran ketones in white snakeroot populations that cause toxicosis have not been documented. The objectives of this study were to compare the toxicity of seven plant populations, better characterize the clinical and pathologic changes of poisoning, and correlate intoxication with benzofuran ketone content. Four of the seven white snakeroot collections were toxic at the dose and duration used in the study. Affected goats became exercise intolerant, had significant serum enzyme changes and histological lesions in the large appendicular muscles. The incidence and severity of poisoning was not correlated with total doses of Tremetone or total benzofuran ketone concentrations suggesting they may not be closely involved in producing toxicity and the possible involvement of an unidentified toxin. The results also demonstrate that white snakeroot populations vary chemically and toxicologically.
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Toxicity of White Snakeroot (Ageratina altissima) and Chemical Extracts of White Snakeroot in Goats
2015Co-Authors: Zane T Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Mark G. Collett, Steven R Buck, James A. PfisterAbstract:White snakeroot (Ageratina altissima) is a sporadically toxic plant that causes trembles in livestock and milk sickness in humans that drink tainted milk. The putative toxin in white snakeroot is Tremetone and possibly other benzofuran ketones, even though it has not been demonstrated in vivo. Toxic white snakeroot was dosed to goats, and they developed clinical signs of poisoning, exercise intolerance, significant increases in serum enzyme activities, and histological changes. Tremetone and the other benzofuran ketones were extracted with hexane; the extracts and residues were analyzed for Tremetone and dosed to goats at Tremetone and benzofuran ketone concentrations similar to the original plant material. However, none of the dosed goats developed the disease. The results demonstrate for the first time that white snakeroot is a potent myotoxin in goats and that other compound(s), which may be lost or modified during the extraction process, could be involved in causing trembles and milk sickness
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A Survey of Tremetone, DehydroTremetone, and Structurally Related Compounds in Isocoma spp. (Goldenbush) in the Southwestern United States
2015Co-Authors: Stephen T. Lee, Dale R. Gardner, Daniel Cook, Zane T Davis, Robert L. Johnson, Clinton A. StonecipherAbstract:Isocoma pluriflora, a plant prevalent on land used for livestock production and native to Arizona, New Mexico, West Texas, and Northern Mexico, is poisonous and causes trembles in livestock. Tremetone and dehydroTremetone have been suggested as the toxic compounds in I. pluriflora. In this study several different Isocoma spp., including I. pluriflora, I. tenuisecta, I. azteca, I. acradenia, and I. rusbyi, that are native to land used for grazing livestock in the southwestern United States were analyzed by high performance liquid chromatography (HPLC) for Tremetone, dehydroTremetone, and other structurally related compounds. This is the first report of Tremetone, dehydroTremetone, and 3-oxyangeloylTremetone in I. tenuisecta, I. azteca, I. acradenia, I. rusbyi, and several other Isocoma spp. In addition, this is the first report of 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone and 7-isopentenyloxycoumarin in Isocoma spp
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physiological and serum biochemical changes associated with rayless goldenrod isocoma pluriflora poisoning in goats
Toxicon, 2013Co-Authors: Zane T Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Kevin D Welch, James A. PfisterAbstract:Rayless goldenrod (Isocoma pluriflora) has been known to be toxic to livestock in the southwestern United States for many years; however, chemical composition of the plant as well as the dosage and duration required to cause toxicosis have not been completely described. Tremetol, the historical toxin, is actually a mixture of alcohols and ketones. Though not completely confirmed experimentally, the toxic compounds are believed to be benzofuran ketones that include Tremetone, dehydroTremetone, 3-hydroxyTremetone, and 3-oxyangeloyl-Tremetone. The objectives of this study were to determine the dosage of benzofuran ketones and the duration of exposure to these compounds required to produce clinical signs of poisoning in Spanish goats and to document the pathophysiological changes associated with rayless goldenrod poisoning in goats. Goats dosed with rayless goldenrod containing 40 and 60 mg/kg BW of benzofuran ketones for 4 or 5 days, showed clinical signs of toxicosis that included trembles, and exercise intolerance seen as reluctance to perform on the treadmill, significantly increased resting and working heart rates and prolonged heart rate recovery following exercise. The affected goats also had significant serum biochemical changes that included increased concentrations of cardiac troponin I and increased activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase. Exercise intolerant animals also had extensive degeneration and necrosis within nearly all skeletal muscles. Some goats dosed with 10 and 20 mg/kg BW of benzofuran ketones began to show some signs of poisoning on the last day of the study. In conclusion, benzofuran ketones at doses at or above 40 mg/kg BW for longer than 4 or 5 days are toxic and produce disease similar to that described in clinical rayless goldenrod poisoning. Additionally, smaller benzofuran ketone doses (10 and 20 mg/kg BW) for longer durations also cause the disease. The physiologic findings indicated that though there may be some myocardial changes, the majority of the clinical disease in goats is due to skeletal muscle degeneration and necrosis. More work is needed to determine the toxicity and physiologic effects of individual benzofuran ketones and to develop a model that better predicts the risk of poisoning and methods to avoid poisoning by plants containing benzofuran ketones.
Bryan L. Stegelmeier - One of the best experts on this subject based on the ideXlab platform.
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white snakeroot poisoning in goats variations in toxicity with different plant chemotypes
Research in Veterinary Science, 2016Co-Authors: T.z. Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Tim J. Evans, James A. Pfister, M G Collett, Daniel Grum, S BuckAbstract:Tremetone and possibly other benzofuran ketones are believed to be the toxic compounds in white snakeroot. However, disease has not been reproduced with purified toxins and the concentrations of the benzofuran ketones in white snakeroot populations that cause toxicosis have not been documented. The objectives of this study were to compare the toxicity of seven plant populations, better characterize the clinical and pathologic changes of poisoning, and correlate intoxication with benzofuran ketone content. Four of the seven white snakeroot collections were toxic at the dose and duration used in the study. Affected goats became exercise intolerant, had significant serum enzyme changes and histological lesions in the large appendicular muscles. The incidence and severity of poisoning was not correlated with total doses of Tremetone or total benzofuran ketone concentrations suggesting they may not be closely involved in producing toxicity and the possible involvement of an unidentified toxin. The results also demonstrate that white snakeroot populations vary chemically and toxicologically.
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Toxicity of White Snakeroot (Ageratina altissima) and Chemical Extracts of White Snakeroot in Goats
2015Co-Authors: Zane T Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Mark G. Collett, Steven R Buck, James A. PfisterAbstract:White snakeroot (Ageratina altissima) is a sporadically toxic plant that causes trembles in livestock and milk sickness in humans that drink tainted milk. The putative toxin in white snakeroot is Tremetone and possibly other benzofuran ketones, even though it has not been demonstrated in vivo. Toxic white snakeroot was dosed to goats, and they developed clinical signs of poisoning, exercise intolerance, significant increases in serum enzyme activities, and histological changes. Tremetone and the other benzofuran ketones were extracted with hexane; the extracts and residues were analyzed for Tremetone and dosed to goats at Tremetone and benzofuran ketone concentrations similar to the original plant material. However, none of the dosed goats developed the disease. The results demonstrate for the first time that white snakeroot is a potent myotoxin in goats and that other compound(s), which may be lost or modified during the extraction process, could be involved in causing trembles and milk sickness
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physiological and serum biochemical changes associated with rayless goldenrod isocoma pluriflora poisoning in goats
Toxicon, 2013Co-Authors: Zane T Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Kevin D Welch, James A. PfisterAbstract:Rayless goldenrod (Isocoma pluriflora) has been known to be toxic to livestock in the southwestern United States for many years; however, chemical composition of the plant as well as the dosage and duration required to cause toxicosis have not been completely described. Tremetol, the historical toxin, is actually a mixture of alcohols and ketones. Though not completely confirmed experimentally, the toxic compounds are believed to be benzofuran ketones that include Tremetone, dehydroTremetone, 3-hydroxyTremetone, and 3-oxyangeloyl-Tremetone. The objectives of this study were to determine the dosage of benzofuran ketones and the duration of exposure to these compounds required to produce clinical signs of poisoning in Spanish goats and to document the pathophysiological changes associated with rayless goldenrod poisoning in goats. Goats dosed with rayless goldenrod containing 40 and 60 mg/kg BW of benzofuran ketones for 4 or 5 days, showed clinical signs of toxicosis that included trembles, and exercise intolerance seen as reluctance to perform on the treadmill, significantly increased resting and working heart rates and prolonged heart rate recovery following exercise. The affected goats also had significant serum biochemical changes that included increased concentrations of cardiac troponin I and increased activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase. Exercise intolerant animals also had extensive degeneration and necrosis within nearly all skeletal muscles. Some goats dosed with 10 and 20 mg/kg BW of benzofuran ketones began to show some signs of poisoning on the last day of the study. In conclusion, benzofuran ketones at doses at or above 40 mg/kg BW for longer than 4 or 5 days are toxic and produce disease similar to that described in clinical rayless goldenrod poisoning. Additionally, smaller benzofuran ketone doses (10 and 20 mg/kg BW) for longer durations also cause the disease. The physiologic findings indicated that though there may be some myocardial changes, the majority of the clinical disease in goats is due to skeletal muscle degeneration and necrosis. More work is needed to determine the toxicity and physiologic effects of individual benzofuran ketones and to develop a model that better predicts the risk of poisoning and methods to avoid poisoning by plants containing benzofuran ketones.
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Experimental rayless goldenrod (Isocoma pluriflora) toxicosis in horses
Toxicon : official journal of the International Society on Toxinology, 2013Co-Authors: T.z. Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Jeffery O. HallAbstract:Rayless goldenrod (Isocoma pluriflora) sporadically poisons horses and other livestock in the southwestern United States. Similar to livestock poisoning by white snakeroot (Ageratina altissima) in the midwestern United States, previous research suggests that benzofuran ketones (BFK: Tremetone, dehydroTremetone, 6-hydroxyTremetone, and 3-oxyangeloyl-Tremetone) are responsible for the toxicity of rayless goldenrod. However, experimental reproduction of rayless goldenrod-induced disease and detailed descriptions of poisoning in horses with known concentrations of Tremetone and other BFK has not been documented. In this study four horses were fed increasing amounts of rayless goldenrod to obtain doses of approximately 0, 10, 30, and 60 mg BFK/kg BW for 14 days. After seven days of dosing the horse dosed with 60 mg BFK/kg BW horse developed depression, reluctance to eat, dehydration, trembling, and muscle fatigue. Biochemical alterations including increases in the serum enzyme activities of CK, AST, ALT, and LDH, and increased cardiac troponin I concentration, were also identified. Physiologically the clinically poisoned horse had decreased endurance seen as reluctance to perform on the treadmill with increased resting heart rate and a prolonged recovery of heart rate following treadmill exercise. The condition of the horse continued to decline and it was euthanized and necropsied on day 10. At necropsy the myocardium was pale and soft and many of the appendicular and large apical muscles were pale and moist. Histologically, the myocardium had extensive myocardial degeneration and necrosis with extensive fibrosis and multifocal mineralization. Several of the large appendicular muscles in this horse also had small foci of skeletal muscle degeneration and necrosis. Less severe myocardial changes were also identified in the horse dosed with 30 mg BFK/kg BW after 14 days of dosing. No clinical, biochemical or histologic changes were identified in the control horse and the horse dosed with 10 mg BFK/kg BW. These results suggest that doses of 60 mg BFK/kg BW for seven days produce extensive myocardial lesions in horses. The horse dosed with 30 mg BFK/kg BW developed less severe, but similar myocardial lesions over a longer duration, this suggests that poisoning may be cumulative and lower doses of longer duration are also toxic. Horses seem to be uniquely sensitive to rayless goldenrod-induced myocardial disease, therefore cardiac troponin I may be a useful marker of rayless goldenrod poisoning in horses. More work is needed to determine which BFK produce myocardial toxicity and better determine the effects of dose and duration on poisoning in horses.
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Evaluation of Drying Methods and Toxicity of Rayless Goldenrod (Isocoma pluriflora) and White Snakeroot (Ageratina altissima) in Goats
Journal of agricultural and food chemistry, 2012Co-Authors: Stephen T. Lee, T. Zane Davis, Daniel Cook, Bryan L. StegelmeierAbstract:White snakeroot and rayless goldenrod cause “trembles” and “milk sickness” in livestock and humans, respectively. The toxin in white snakeroot and rayless goldenrod was identified in 1927 and 1930, respectively, as tremetol. It was reported that the toxin in white snakeroot disappears as it is dried and that completely dried plants were incapable of producing trembles or milk sickness. Conversely, it has been reported that the rayless goldenrod toxin was not destroyed by drying and that the plant is toxic either fresh or dry. In this study the concentrations of Tremetone, dehydroTremetone, and structurally similar compounds were determined in white snakeroot and rayless goldenrod before and after various drying conditions. Tremetone, dehydroTremetone, and structurally similar compounds in rayless goldenrod and white snakeroot are most stable upon freeze-drying, followed by air-drying, and least stable upon oven-drying (60 °C). Also demonstrated is that Tremetone is stable and that dried white snakeroot an...
Zane T Davis - One of the best experts on this subject based on the ideXlab platform.
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microsomal activation and sh sy5y cell toxicity studies of Tremetone and 6 hydroxyTremetone isolated from rayless goldenrod isocoma pluriflora and white snakeroot agertina altissima respectively
Toxicon: X, 2020Co-Authors: Benedict T. Green, Stephen T. Lee, Zane T Davis, Kevin D WelchAbstract:Abstract This research compared the cytotoxic actions of the benzofuran ketone, Tremetone in B16 murine melanoma cells to SH-SY5Y human neuroblastoma cells with an MTT assay. Tremetone was not cytotoxic in B16 cells. In SH-SY5Y cells, concentration-dependent Tremetone cytotoxicity occurred without microsomal activation. No cytotoxicity was observed with 6-hydroxyTremetone. This suggests that SH-SY5Y cells are a better model for the cytotoxic actions of Tremetone and that Tremetone is toxic without microsomal activation.
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Toxicity of White Snakeroot (Ageratina altissima) and Chemical Extracts of White Snakeroot in Goats
2015Co-Authors: Zane T Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Mark G. Collett, Steven R Buck, James A. PfisterAbstract:White snakeroot (Ageratina altissima) is a sporadically toxic plant that causes trembles in livestock and milk sickness in humans that drink tainted milk. The putative toxin in white snakeroot is Tremetone and possibly other benzofuran ketones, even though it has not been demonstrated in vivo. Toxic white snakeroot was dosed to goats, and they developed clinical signs of poisoning, exercise intolerance, significant increases in serum enzyme activities, and histological changes. Tremetone and the other benzofuran ketones were extracted with hexane; the extracts and residues were analyzed for Tremetone and dosed to goats at Tremetone and benzofuran ketone concentrations similar to the original plant material. However, none of the dosed goats developed the disease. The results demonstrate for the first time that white snakeroot is a potent myotoxin in goats and that other compound(s), which may be lost or modified during the extraction process, could be involved in causing trembles and milk sickness
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A Survey of Tremetone, DehydroTremetone, and Structurally Related Compounds in Isocoma spp. (Goldenbush) in the Southwestern United States
2015Co-Authors: Stephen T. Lee, Dale R. Gardner, Daniel Cook, Zane T Davis, Robert L. Johnson, Clinton A. StonecipherAbstract:Isocoma pluriflora, a plant prevalent on land used for livestock production and native to Arizona, New Mexico, West Texas, and Northern Mexico, is poisonous and causes trembles in livestock. Tremetone and dehydroTremetone have been suggested as the toxic compounds in I. pluriflora. In this study several different Isocoma spp., including I. pluriflora, I. tenuisecta, I. azteca, I. acradenia, and I. rusbyi, that are native to land used for grazing livestock in the southwestern United States were analyzed by high performance liquid chromatography (HPLC) for Tremetone, dehydroTremetone, and other structurally related compounds. This is the first report of Tremetone, dehydroTremetone, and 3-oxyangeloylTremetone in I. tenuisecta, I. azteca, I. acradenia, I. rusbyi, and several other Isocoma spp. In addition, this is the first report of 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone and 7-isopentenyloxycoumarin in Isocoma spp
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physiological and serum biochemical changes associated with rayless goldenrod isocoma pluriflora poisoning in goats
Toxicon, 2013Co-Authors: Zane T Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Kevin D Welch, James A. PfisterAbstract:Rayless goldenrod (Isocoma pluriflora) has been known to be toxic to livestock in the southwestern United States for many years; however, chemical composition of the plant as well as the dosage and duration required to cause toxicosis have not been completely described. Tremetol, the historical toxin, is actually a mixture of alcohols and ketones. Though not completely confirmed experimentally, the toxic compounds are believed to be benzofuran ketones that include Tremetone, dehydroTremetone, 3-hydroxyTremetone, and 3-oxyangeloyl-Tremetone. The objectives of this study were to determine the dosage of benzofuran ketones and the duration of exposure to these compounds required to produce clinical signs of poisoning in Spanish goats and to document the pathophysiological changes associated with rayless goldenrod poisoning in goats. Goats dosed with rayless goldenrod containing 40 and 60 mg/kg BW of benzofuran ketones for 4 or 5 days, showed clinical signs of toxicosis that included trembles, and exercise intolerance seen as reluctance to perform on the treadmill, significantly increased resting and working heart rates and prolonged heart rate recovery following exercise. The affected goats also had significant serum biochemical changes that included increased concentrations of cardiac troponin I and increased activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase. Exercise intolerant animals also had extensive degeneration and necrosis within nearly all skeletal muscles. Some goats dosed with 10 and 20 mg/kg BW of benzofuran ketones began to show some signs of poisoning on the last day of the study. In conclusion, benzofuran ketones at doses at or above 40 mg/kg BW for longer than 4 or 5 days are toxic and produce disease similar to that described in clinical rayless goldenrod poisoning. Additionally, smaller benzofuran ketone doses (10 and 20 mg/kg BW) for longer durations also cause the disease. The physiologic findings indicated that though there may be some myocardial changes, the majority of the clinical disease in goats is due to skeletal muscle degeneration and necrosis. More work is needed to determine the toxicity and physiologic effects of individual benzofuran ketones and to develop a model that better predicts the risk of poisoning and methods to avoid poisoning by plants containing benzofuran ketones.
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quantitative method for the measurement of three benzofuran ketones in rayless goldenrod isocoma pluriflora and white snakeroot ageratina altissima by high performance liquid chromatography hplc
Journal of Agricultural and Food Chemistry, 2009Co-Authors: Stephen T. Lee, Dale R. Gardner, Bryan L. Stegelmeier, Zane T Davis, Tim J. EvansAbstract:White snakeroot ( Ageratina altissima ) and rayless goldenrod ( Isocoma pluriflora ) can cause "trembles" and "milk sickness" in livestock and humans, respectively. Tremetol, a complex mixture of sterols and derivatives of methyl ketone benzofuran has been extracted from white snakeroot and rayless goldenrod and is reported to be the toxic substance in plant material. In this study, the three major benzofuran ketones, Tremetone, dehydroTremetone, and 3-oxyangeloyl-Tremetone, were isolated from rayless goldenrod. Using these compounds as standards, a quantitative high-performance liquid chromatography (HPLC) method was developed to measure these compounds in white snakeroot and rayless goldenrod. Concentrations of Tremetone, dehydroTremetone, and 3-oxyangeloyl-Tremetone were found to vary considerably among the different white snakeroot and rayless goldenrod plant collections. Differences in concentrations of Tremetone, dehydroTremetone, and 3-oxyangeloyl-Tremetone in white snakeroot and rayless goldenrod plants may explain the historical sporadic and unpredictable toxicity of these plants to livestock and humans.
Benedict T. Green - One of the best experts on this subject based on the ideXlab platform.
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microsomal activation and sh sy5y cell toxicity studies of Tremetone and 6 hydroxyTremetone isolated from rayless goldenrod isocoma pluriflora and white snakeroot agertina altissima respectively
Toxicon: X, 2020Co-Authors: Benedict T. Green, Stephen T. Lee, Zane T Davis, Kevin D WelchAbstract:Abstract This research compared the cytotoxic actions of the benzofuran ketone, Tremetone in B16 murine melanoma cells to SH-SY5Y human neuroblastoma cells with an MTT assay. Tremetone was not cytotoxic in B16 cells. In SH-SY5Y cells, concentration-dependent Tremetone cytotoxicity occurred without microsomal activation. No cytotoxicity was observed with 6-hydroxyTremetone. This suggests that SH-SY5Y cells are a better model for the cytotoxic actions of Tremetone and that Tremetone is toxic without microsomal activation.
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white snakeroot poisoning in goats variations in toxicity with different plant chemotypes
Research in Veterinary Science, 2016Co-Authors: T.z. Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Tim J. Evans, James A. Pfister, M G Collett, Daniel Grum, S BuckAbstract:Tremetone and possibly other benzofuran ketones are believed to be the toxic compounds in white snakeroot. However, disease has not been reproduced with purified toxins and the concentrations of the benzofuran ketones in white snakeroot populations that cause toxicosis have not been documented. The objectives of this study were to compare the toxicity of seven plant populations, better characterize the clinical and pathologic changes of poisoning, and correlate intoxication with benzofuran ketone content. Four of the seven white snakeroot collections were toxic at the dose and duration used in the study. Affected goats became exercise intolerant, had significant serum enzyme changes and histological lesions in the large appendicular muscles. The incidence and severity of poisoning was not correlated with total doses of Tremetone or total benzofuran ketone concentrations suggesting they may not be closely involved in producing toxicity and the possible involvement of an unidentified toxin. The results also demonstrate that white snakeroot populations vary chemically and toxicologically.
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Toxicity of White Snakeroot (Ageratina altissima) and Chemical Extracts of White Snakeroot in Goats
2015Co-Authors: Zane T Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Mark G. Collett, Steven R Buck, James A. PfisterAbstract:White snakeroot (Ageratina altissima) is a sporadically toxic plant that causes trembles in livestock and milk sickness in humans that drink tainted milk. The putative toxin in white snakeroot is Tremetone and possibly other benzofuran ketones, even though it has not been demonstrated in vivo. Toxic white snakeroot was dosed to goats, and they developed clinical signs of poisoning, exercise intolerance, significant increases in serum enzyme activities, and histological changes. Tremetone and the other benzofuran ketones were extracted with hexane; the extracts and residues were analyzed for Tremetone and dosed to goats at Tremetone and benzofuran ketone concentrations similar to the original plant material. However, none of the dosed goats developed the disease. The results demonstrate for the first time that white snakeroot is a potent myotoxin in goats and that other compound(s), which may be lost or modified during the extraction process, could be involved in causing trembles and milk sickness
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physiological and serum biochemical changes associated with rayless goldenrod isocoma pluriflora poisoning in goats
Toxicon, 2013Co-Authors: Zane T Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Kevin D Welch, James A. PfisterAbstract:Rayless goldenrod (Isocoma pluriflora) has been known to be toxic to livestock in the southwestern United States for many years; however, chemical composition of the plant as well as the dosage and duration required to cause toxicosis have not been completely described. Tremetol, the historical toxin, is actually a mixture of alcohols and ketones. Though not completely confirmed experimentally, the toxic compounds are believed to be benzofuran ketones that include Tremetone, dehydroTremetone, 3-hydroxyTremetone, and 3-oxyangeloyl-Tremetone. The objectives of this study were to determine the dosage of benzofuran ketones and the duration of exposure to these compounds required to produce clinical signs of poisoning in Spanish goats and to document the pathophysiological changes associated with rayless goldenrod poisoning in goats. Goats dosed with rayless goldenrod containing 40 and 60 mg/kg BW of benzofuran ketones for 4 or 5 days, showed clinical signs of toxicosis that included trembles, and exercise intolerance seen as reluctance to perform on the treadmill, significantly increased resting and working heart rates and prolonged heart rate recovery following exercise. The affected goats also had significant serum biochemical changes that included increased concentrations of cardiac troponin I and increased activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase. Exercise intolerant animals also had extensive degeneration and necrosis within nearly all skeletal muscles. Some goats dosed with 10 and 20 mg/kg BW of benzofuran ketones began to show some signs of poisoning on the last day of the study. In conclusion, benzofuran ketones at doses at or above 40 mg/kg BW for longer than 4 or 5 days are toxic and produce disease similar to that described in clinical rayless goldenrod poisoning. Additionally, smaller benzofuran ketone doses (10 and 20 mg/kg BW) for longer durations also cause the disease. The physiologic findings indicated that though there may be some myocardial changes, the majority of the clinical disease in goats is due to skeletal muscle degeneration and necrosis. More work is needed to determine the toxicity and physiologic effects of individual benzofuran ketones and to develop a model that better predicts the risk of poisoning and methods to avoid poisoning by plants containing benzofuran ketones.
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Experimental rayless goldenrod (Isocoma pluriflora) toxicosis in horses
Toxicon : official journal of the International Society on Toxinology, 2013Co-Authors: T.z. Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Jeffery O. HallAbstract:Rayless goldenrod (Isocoma pluriflora) sporadically poisons horses and other livestock in the southwestern United States. Similar to livestock poisoning by white snakeroot (Ageratina altissima) in the midwestern United States, previous research suggests that benzofuran ketones (BFK: Tremetone, dehydroTremetone, 6-hydroxyTremetone, and 3-oxyangeloyl-Tremetone) are responsible for the toxicity of rayless goldenrod. However, experimental reproduction of rayless goldenrod-induced disease and detailed descriptions of poisoning in horses with known concentrations of Tremetone and other BFK has not been documented. In this study four horses were fed increasing amounts of rayless goldenrod to obtain doses of approximately 0, 10, 30, and 60 mg BFK/kg BW for 14 days. After seven days of dosing the horse dosed with 60 mg BFK/kg BW horse developed depression, reluctance to eat, dehydration, trembling, and muscle fatigue. Biochemical alterations including increases in the serum enzyme activities of CK, AST, ALT, and LDH, and increased cardiac troponin I concentration, were also identified. Physiologically the clinically poisoned horse had decreased endurance seen as reluctance to perform on the treadmill with increased resting heart rate and a prolonged recovery of heart rate following treadmill exercise. The condition of the horse continued to decline and it was euthanized and necropsied on day 10. At necropsy the myocardium was pale and soft and many of the appendicular and large apical muscles were pale and moist. Histologically, the myocardium had extensive myocardial degeneration and necrosis with extensive fibrosis and multifocal mineralization. Several of the large appendicular muscles in this horse also had small foci of skeletal muscle degeneration and necrosis. Less severe myocardial changes were also identified in the horse dosed with 30 mg BFK/kg BW after 14 days of dosing. No clinical, biochemical or histologic changes were identified in the control horse and the horse dosed with 10 mg BFK/kg BW. These results suggest that doses of 60 mg BFK/kg BW for seven days produce extensive myocardial lesions in horses. The horse dosed with 30 mg BFK/kg BW developed less severe, but similar myocardial lesions over a longer duration, this suggests that poisoning may be cumulative and lower doses of longer duration are also toxic. Horses seem to be uniquely sensitive to rayless goldenrod-induced myocardial disease, therefore cardiac troponin I may be a useful marker of rayless goldenrod poisoning in horses. More work is needed to determine which BFK produce myocardial toxicity and better determine the effects of dose and duration on poisoning in horses.
James A. Pfister - One of the best experts on this subject based on the ideXlab platform.
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white snakeroot poisoning in goats variations in toxicity with different plant chemotypes
Research in Veterinary Science, 2016Co-Authors: T.z. Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Tim J. Evans, James A. Pfister, M G Collett, Daniel Grum, S BuckAbstract:Tremetone and possibly other benzofuran ketones are believed to be the toxic compounds in white snakeroot. However, disease has not been reproduced with purified toxins and the concentrations of the benzofuran ketones in white snakeroot populations that cause toxicosis have not been documented. The objectives of this study were to compare the toxicity of seven plant populations, better characterize the clinical and pathologic changes of poisoning, and correlate intoxication with benzofuran ketone content. Four of the seven white snakeroot collections were toxic at the dose and duration used in the study. Affected goats became exercise intolerant, had significant serum enzyme changes and histological lesions in the large appendicular muscles. The incidence and severity of poisoning was not correlated with total doses of Tremetone or total benzofuran ketone concentrations suggesting they may not be closely involved in producing toxicity and the possible involvement of an unidentified toxin. The results also demonstrate that white snakeroot populations vary chemically and toxicologically.
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Toxicity of White Snakeroot (Ageratina altissima) and Chemical Extracts of White Snakeroot in Goats
2015Co-Authors: Zane T Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Mark G. Collett, Steven R Buck, James A. PfisterAbstract:White snakeroot (Ageratina altissima) is a sporadically toxic plant that causes trembles in livestock and milk sickness in humans that drink tainted milk. The putative toxin in white snakeroot is Tremetone and possibly other benzofuran ketones, even though it has not been demonstrated in vivo. Toxic white snakeroot was dosed to goats, and they developed clinical signs of poisoning, exercise intolerance, significant increases in serum enzyme activities, and histological changes. Tremetone and the other benzofuran ketones were extracted with hexane; the extracts and residues were analyzed for Tremetone and dosed to goats at Tremetone and benzofuran ketone concentrations similar to the original plant material. However, none of the dosed goats developed the disease. The results demonstrate for the first time that white snakeroot is a potent myotoxin in goats and that other compound(s), which may be lost or modified during the extraction process, could be involved in causing trembles and milk sickness
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physiological and serum biochemical changes associated with rayless goldenrod isocoma pluriflora poisoning in goats
Toxicon, 2013Co-Authors: Zane T Davis, Stephen T. Lee, Benedict T. Green, Bryan L. Stegelmeier, Kevin D Welch, James A. PfisterAbstract:Rayless goldenrod (Isocoma pluriflora) has been known to be toxic to livestock in the southwestern United States for many years; however, chemical composition of the plant as well as the dosage and duration required to cause toxicosis have not been completely described. Tremetol, the historical toxin, is actually a mixture of alcohols and ketones. Though not completely confirmed experimentally, the toxic compounds are believed to be benzofuran ketones that include Tremetone, dehydroTremetone, 3-hydroxyTremetone, and 3-oxyangeloyl-Tremetone. The objectives of this study were to determine the dosage of benzofuran ketones and the duration of exposure to these compounds required to produce clinical signs of poisoning in Spanish goats and to document the pathophysiological changes associated with rayless goldenrod poisoning in goats. Goats dosed with rayless goldenrod containing 40 and 60 mg/kg BW of benzofuran ketones for 4 or 5 days, showed clinical signs of toxicosis that included trembles, and exercise intolerance seen as reluctance to perform on the treadmill, significantly increased resting and working heart rates and prolonged heart rate recovery following exercise. The affected goats also had significant serum biochemical changes that included increased concentrations of cardiac troponin I and increased activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase. Exercise intolerant animals also had extensive degeneration and necrosis within nearly all skeletal muscles. Some goats dosed with 10 and 20 mg/kg BW of benzofuran ketones began to show some signs of poisoning on the last day of the study. In conclusion, benzofuran ketones at doses at or above 40 mg/kg BW for longer than 4 or 5 days are toxic and produce disease similar to that described in clinical rayless goldenrod poisoning. Additionally, smaller benzofuran ketone doses (10 and 20 mg/kg BW) for longer durations also cause the disease. The physiologic findings indicated that though there may be some myocardial changes, the majority of the clinical disease in goats is due to skeletal muscle degeneration and necrosis. More work is needed to determine the toxicity and physiologic effects of individual benzofuran ketones and to develop a model that better predicts the risk of poisoning and methods to avoid poisoning by plants containing benzofuran ketones.
