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Plasma l-indospicine and 3-nitropropionic acid in ponies fed creeping indigo: Comparison with results from an episode of presumptive creeping indigo toxicosis.
Abstract: Creeping indigo (Indigofera spicata) toxicosis is an emerging problem among horses in Florida and bordering states. Objective: To quantify the putative toxins l-indospicine (IND) and 3-nitropropionic acid (NPA) in creeping indigo collected from multiple sites and to measure plasma toxin concentrations in ponies fed creeping indigo and horses with presumptive creeping indigo toxicosis. Methods: Experimental descriptive study with descriptive observational field investigation. Methods: Air-dried creeping indigo was assayed for IND and NPA content. Five ponies were fed chopped creeping indigo containing 1 mg/kg/day of IND and trace amounts of NPA for 5 days, then observed for 28 days. Blood samples from these ponies and from horses involved in a presumptive creeping indigo toxicosis were assayed for IND and NPA. Results: IND in creeping indigo plants was 0.4-3.5 mg/g dry matter whereas NPA was <0.01 to 0.03 mg/g. During creeping indigo feeding, clinical and laboratory signs were unchanged except for significant weight loss (median 6%, range 2%-9%; p = .04) and significant increase from baseline plasma protein concentration (median 16 g/L, range 8-25 g/L; p < .001). These changes could not definitively be ascribed to creeping indigo ingestion. Plasma IND rose to 3.9 ± 0.52 mg/L on day 6. Pharmacokinetic modelling indicated an elimination half-life of 25 days and a steady state plasma concentration of 22 mg/L. Plasma IND concentration in sick horses during an incident of creeping indigo toxicosis was approximately twice that of clinically normal pasture mates. Plasma NPA was <0.05 mg/L in all samples. Conclusions: Creeping indigo used in the feeding trial may not be representative of plants involved in creeping indigo toxicosis. There was no control group without creeping indigo in the feeding trial. Conclusions: Indospicine can be detected in blood of horses consuming creeping indigo and the toxin accumulates in tissues and clears slowly. The role of NPA in the neurological signs of this syndrome is unclear.
© 2020 EVJ Ltd.
Publication Date: 2021-02-15 PubMed ID: 33369767DOI: 10.1111/evj.13415Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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The research article focuses on the toxic effects of creeping indigo (Indigofera spicata), specifically l-indospicine (IND) and 3-nitropropionic acid (NPA), on ponies and horses. These toxins were sampled from places where the plant was abundant and measured in ponies that consumed it and horses that experienced a toxic reaction to it.
Methods
- The toxins from the creeping indigo plant collected from multiple locations were quantified. The toxins quantified were the l-indospicine and 3-nitropropionic acid.
- Five ponies were then fed the chopped creeping indigo containing 1mg/kg/day of l-indospicine and trace quantities of 3-nitropropionic acid over a period of 5 days. They were then observed for 28 days post feeding.
- Simultaneously, blood samples from these ponies and horses that showed signs of creeping indigo toxicosis were also examined for traces of these toxins.
Results
- The results showed that l-indospicine in the creeping indigo plants ranged between 0.4-3.5 mg/g of dry matter, whereas 3-nitropropionic acid was less than 0.01 to 0.03 mg/g.
- The ponies that were fed creeping indigo showed no clinical or laboratory changes, except for a significant weight loss, and an increase from the baseline plasma protein concentration.
- It was challenging to directly link these changes to the ingestion of creeping indigo due to lack of a control group.
- Post feeding, the plasma l-indospicine concentration rose to 3.9 mg/L on day 6. Further, a pharmacokinetic modelling indicated that the elimination half-life of l-indospicine was roughly 25 days, achieving a stable state of plasma concentration at 22 mg/L.
- Observations showed that during an episode of creeping indigo toxicosis, sick horses exhibited nearly twice the plasma concentration of l-indospicine compared to the unaffected ones grazing in the same pasture.
- The concentration of 3-nitropropionic acid was less than 0.05 mg/L across all samples.
Conclusions
- The creeping indigo used for the feeding trials might not accurately represent the plants involved in creeping indigo toxicosis episodes. This is primarily due to the absence of a control group not consuming the plant.
- l-Indospicine could be detected in the blood samples of horses that consumed creeping indigo, and this toxin tends to accumulate in the body and clears slowly.
- Uncertainty surrounded the role of 3-nitropropionic acid in producing neurological signs associated with this toxicosis, due to its marginal concentration in the samples.
Cite This Article
APA
Darby S, Sanchez LC, Mallicote MF, House AM, Plummer CE, Nadruz V, Benmoha RH, Roberts SM, Derendorf H, Silva-Sanchez C, Claire J, MacKay RJ.
(2021).
Plasma l-indospicine and 3-nitropropionic acid in ponies fed creeping indigo: Comparison with results from an episode of presumptive creeping indigo toxicosis.
Equine Vet J, 54(1), 145-152.
https://doi.org/10.1111/evj.13415 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
- Department of Large Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
- Department of Large Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
- Department of Large Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
- Departments of Small and Large Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
- Kansas State University Veterinary Health Center, Manhattan, KS, USA.
- Department of Large Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
- Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, USA.
- Department of Pharmaceutics, University of Florida College of Pharmacy, Gainesville, FL, USA.
- Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, USA.
- Department of Large Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
- Department of Large Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
MeSH Terms
- Animals
- Horse Diseases / chemically induced
- Horses
- Indigo Carmine
- Indigofera
- Nitro Compounds
- Norleucine / analogs & derivatives
- Propionates
Grant Funding
- FLA-VME-005559 / National Institute of Food and Agriculture
References
This article includes 28 references
- Morton JF. Creeping indigo (Indigofera-spicata Forsk) (Fabaceae) - a hazard to herbivores in Florida. Econ Bot. 1989;43:314-27.
- Lima EF, Riet-Correa F, Gardner DR, Barros SS, Medeiros RMT, Soares MP, et al. Poisoning by Indigofera lespedezioides in horses. Toxicon. 2012;60:324-8.
- Ossedryver SM, Baldwin GI, Stone BM, McKenzie RA, van Eps AW, Murray S, et al. Indigofera spicata (creeping indigo) poisoning of three ponies. Aust Vet J. 2013;91:143-9.
- Fletcher MT, Al Jassim RAM, Cawdell-Smith AJ. The occurrence and toxicity of indospicine to grazing animals. Agriculture (Basel). 2015;5:427-40.
- MacKay RJ. Creeping indigo toxicity, Large Animal Hospital. College of Veterinary Medicine; 2014. http://largeanimal.vethospitals.ufl.edu/2014/11/03/creeping-indigo-toxicity/
- Nordfeldt S, Henke LA, Morita K, Matsumoto H, Takahashi M, Younge OR, et al. Feeding tests with Indigofera endecaphylla Jacq. (creeping indigo) and some observations on its poisonous effects on domestic animals. Hawaii Agric Exp Sta Tech Bull. 1952;15:1-23.
- Hegarty MP, Pound AW. Indospicine, a hepatotoxic amino acid from Indigofera spicata - isolation, structure, and biological studies. Aust J Biol Sci. 1970;23:831-42.
- Hegarty MP, Pound AW. Indospicine, a new hepatotoxic amino-acid from Indigofera spicata. Nature. 1968;217:354-5.
- Gardner DR, Riet-Correa F. Analysis of the toxic amino acid indospicine by liquid chromatography-tandem mass spectrometry. Int J Poisonous Plant Res. 2011;1:20-7.
- Tan ET, Materne CM, Silcock RG, D'Arcy BR, Al Jassim R, Fletcher MT. Seasonal and species variation of the hepatotoxin indospicine in Australian Indigofera legumes as measured by UPLC-MS/MS. J Agric Food Chem. 2016;64:6613-21.
- Pollitt S, Hegarty MP, Pass MA. Analysis of the amino acid indospicine in biological samples by high performance liquid chromatography. Nat Toxins. 1999;7:233-40.
- Brownell AL, Chen YI, Yu MX, Wang XK, Dedeoglu A, Cicchetti F, et al. 3-Nitropropionic acid-induced neurotoxicity - assessed by ultra high resolution positron emission tomography with comparison to magnetic resonance spectroscopy. J Neurochem. 2004;89:1206-14.
- Rose AL, Banks AW, McConnell JD. Birdsville disease in the Northern Territory. Aust Vet J. 1951;27:189-96.
- Hopper PT, Hart B, Smith GW. Prevention and treatment of Birdsville disease of horses. Aust Vet J. 1971;47:326-9.
- Tan ET, Al Jassim R, Cawdell-Smith AJ, Ossedryver SM, D'Arcy BR, Fletcher MT. Accumulation, persistence, and effects of indospicine residues in camels fed Indigofera plant. J Agric Food Chem. 2016;64:6622-9.
- Liu H, Liu G, Kang L, Chen Y, Jiang J. Determination of 3-nitropropionic acid in poisoning samples by ultra-performance liquid chromatography-tandem mass spectrometry. Wei Sheng Yan Jiu. 2016;45:56-60.
- Tan ETT, Al Jassim R, D'Arcy BR, Fletcher MT. In vitro biodegradation of hepatotoxic indospicine in Indigofera spicata and its degradation derivatives by camel foregut and cattle rumen fluids. J Agric Food Chem. 2017;65:7528-34.
- Fletcher MT, Reichmann KG, Ossedryver SM, McKenzie RA, Carter PD, Blaney BJ. Accumulation and depletion of indospicine in calves (Bos taurus) fed creeping indigo (Indigofera spicata). Anim Prod Sci. 2018;58:568-76.
- Young MP. Investigation of the toxicity of horsemeat due to contamination by indospicine. PhD diss., University of Queensland, St. Lucia, Australia; 1992.
- Aylward JH, Court RD, Haydock KP, Strickland RW, Hegarty MP. Indigofera species with agronomic potential in the tropics. Rat toxicity studies. Aust J Agric Res. 1987;38:177-86.
- Majak W, Benn M, McEwan D, Pass MA. 3 Nitropropanoyl esters of glucose from Indigofera linnaei. Phytochemistry. 1992;31:2393-5.
- Pass MA, Majak W, Muir AD, Yost GS. Absorption of 3-nitropropanol and 3-nitropropionic acid from the digestive-system of sheep. Toxicol Lett. 1984;23:1-7.
- Majak W, Pass MA, Muir AD, Rode LM. Absorption of 3-nitropropanol (miserotoxin aglycone) from the compound stomach of cattle. Toxicol Lett. 1984;23:9-15.
- Carroll AG, Swain BJ. Birdsville disease in the central highlands area of Queensland. Aust Vet J. 1983;60:316-7.
- Hegarty MP. Toxic amino acids of plant origin. In: Keeler RF, Van Kampen KR, James LF, editors. Effects of poisonous plants on livestock. St. Louis: Elsevier, 1978; p. 575-85.
- Rosenthal GA, Bell EA. Naturally occurring toxic nonprotein amino acids. In: Rosenthal GA, Janzen DH, Applebaum SW, editors. Herbivores, their interaction with secondary plant metabolites. New York: Academic Press, 1979; p. 353-85.
- Fernagut PO, Diguet E, Stefanova N, Biran M, Wenning GK, Canioni P, et al. Subacute systemic 3-nitropropionic acid intoxication induces a distinct motor disorder in adult C57Bl/6 mice: Behavioural and histopathological characterisation. Neuroscience. 2002;114:1005-17.
- Palfi SP, Ferrante RJ, Brouillet E, Beal MF, Dolan R, Guyot MC, et al. Chronic 3-nitropropionic acid treatment in baboons replicates the cognitive and motor deficits of Huntington's disease. J Neurosci. 1996;16:3019-25.
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