Level of 3‐Nitropropanoic Acid in Relation to Toxicity of <i>Indigofera spicata</i> in Chicks

Britten, E. J.; Palafox, A. L.; Frodyma, Michael M.; Lynd, F. T.

doi:10.2135/cropsci1963.0011183x000300050013x

Cited by 13 publications

(12 citation statements)

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“…It and/or its glycosides have been isolated from such toxic plants as Indigofera endecaphylla (9, 10) and I. spicta (22), Hiptage madablota (23) and H. benghalensis (23), Viola odorata (17), Cornacarpus laevigate (23), and at least five species of Astragalus (24,25). It is also synthesized by the fungi Aspergillus flavus (17), A. orysae (26), and Penicillium atrovenetum (12).…”

Section: Resultsmentioning

confidence: 99%

3-Nitropropionate, the toxic substance of Indigofera , is a suicide inactivator of succinate dehydrogenase

Alston

Mela

Bright

1977

Proc. Natl. Acad. Sci. U.S.A.

363

202

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We have shown that 3-nitropropionate, an isoelectronic analogue of succinate, is a suicide inactivator of succinate dehydrogenase [succinate:(acceptor) However, the precise mechanism of inactivation, as well as mechanistic extrapolations to the oxidation of succinate, must await the elucidation of the structure of the modified enzyme. We can now explain the toxicity of plants such as Indigofera endecaphylla for mammals and fowl as being due to the irreversible blockage of the Krebs cycle by 3-nitropropionate carbanion.Nitroalkanes are good substrates for the flavoenzymes D-amino acid oxidase, glucose oxidase, and L-amino acid oxidase (1-5). The nitroalkane carbanions are many orders of magnitude more reactive than their conjugate carbon acids and, in one case (6), even more reactive than the best physiological substrates (e.g., nitroethane anion compared to glucose with glucose oxidase). Most importantly, and in contrast to any physiological substrate, the chemical mechanism of the enzymic oxidation of nitroalkanes is understood in great detail. For D-amino acid oxidase and nitroethane, it was shown (2) that the substrate carbanion attacks the flavin at N-5 in the rate-determining step to form a covalent adduct (pathway 1 in Eq. 1) from which nitrite is eliminated rapidly to form a highly reactive N-5 iminium adduct. In the normal catalytic cycle (pathway 2 in Eq. 1) the iminium is rapidly hydrated to form an N-5 carbinolamine from which reduced flavin is also rapidly eliminated to form the product acetaldehyde. However, the pivotal N-5 iminium intermediate, as would be expected, is highly reactive with a variety of nucleophiles in addition to H20 (2, 5). Those having unbonded electron pairs (such as NH3, NH20H, and mercap- Second, it occurred to us that, in contrast to D-amino acid oxidase and nitroethane (2)

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Section: Resultsmentioning

confidence: 99%

3-Nitropropionate, the toxic substance of Indigofera , is a suicide inactivator of succinate dehydrogenase

Alston

Mela

Bright

1977

Proc. Natl. Acad. Sci. U.S.A.

363

202

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“…The reason for the mainly neurological disease produced by Indigofera species in horses compared with the liver disease caused by these plants in other animal species has not been thoroughly examined. However, it appears probable that, as in chickens, horses are significantly more susceptible to the 3‐NPA content of the plant than to indospicine. The reverse may be true for ruminants, with evidence suggesting that they can tolerate exposure to plants containing greater concentrations of 3‐NPA through ruminal metabolism .…”

Section: Discussionmentioning

confidence: 99%

“…The first toxin identified in the I. spicata complex was 3‐NPA (3‐nitropropionic acid, β‐nitropropionic acid or hiptagenic acid) . Clinical signs in chicks fed 3‐NPA could not be distinguished from those in chicks fed the plant; however, chicks were not affected by seed material, which contains no 3‐NPA, and dosing of rabbits and mice with 3‐NPA did not produce the expected liver lesions . Subsequently, the hepatotoxic non‐protein amino acid, indospicine, was identified in both seeds and leaves .…”

Section: Current Determinations Of Voucher Specimens From Previous Tomentioning

confidence: 99%

Indigofera spicata (creeping indigo) poisoning of three ponies

Ossedryver¹,

Baldwin

Stone

et al. 2013

Aust Veterinary J

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Three ponies continuously grazed a pasture containing an estimated 24% Indigofera spicata (wet weight basis) for 4-6 weeks in April and May 2004. They developed ataxia, paresis, depression, muscle fasciculations, dysphagia, ptyalism and halitosis. Two also developed corneal opacity. One pony recovered with supportive treatment, but the other two were euthanased and necropsied. Neuropathology was not present in either case, but both livers had periacinar and periportal lymphocytic infiltrations and hydropic degeneration of mid-zonal hepatocytes, with mild to moderate periacinar necrosis also evident in one. The I. spicata contained 2.66 mg 3-nitropropionic acid (3-NPA)/g dry matter and 1.5 mg indospicine/g dry matter. Indospicine, but not 3-NPA, was detected in serum from both of the euthanased ponies and indospicine was detected in heart, liver and muscle from the one pony in which this assay was performed. The clinical syndrome closely resembled 'Birdsville horse disease' caused by I. linnaei and was similar to that reported in horses poisoned by the closely related species I. hendecaphylla and to 3-NPA poisoning of other animals, including humans. 3-NPA is thought to cause this neurological syndrome. To our knowledge, this is the first authenticated report of I. spicata poisoning in grazing animals. We also report here the first published evidence that 3-NPA and indospicine exist in naturalised I. spicata in Australia and of the formation of indospicine residues in tissues of animals grazing paddocks infested with I. spicata.

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“…3–8 Previous phytochemical studies on I. spicata are limited, but have revealed the presence of the toxic amino acids indospicine and canavanine (arginine inhibitors), and of a further toxic compound, 3-nitropropanoic acid, and a non-toxic galactomannan polysaccharide. 9–13 …”

mentioning

confidence: 99%

Bioactive Constituents of Indigofera spicata

Pérez

Lantvit

et al. 2013

J. Nat. Prod.

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Four new flavanones, designated as (+)−5″-deacetylpurpurin (1), (+)−5-methoxypurpurin (2), (2S)-2,3-dihydrotephroglabrin (3), and (2S)-2,3-dihydrotephroapollin C (4), together with two known flavanones (5 and 6), three known rotenoids (7–9), and one known chalcone (10) were isolated from a chloroform-soluble partition of a methanol extract from the combined flowers, fruits, leaves, and twigs of Indigofera spicata, collected in Vietnam. The compounds were obtained by bioactivity-guided isolation using HT-29 human colon cancer, 697 human acute lymphoblastic leukemia, and Raji human Burkitt’s lymphoma cell lines. The structures of 1–4 were established by extensive 1D- and 2D-NMR experiments and the absolute configurations were determined by the measurement of specific rotations and CD spectra. The cytotoxic activities of the isolated compounds were tested against the HT-29, 697, Raji and the CCD-112CoN human normal colon cells. Also, the quinone reductase induction activities of the isolates were determined using the Hepa 1c1c7 murine hepatoma cell line. In addition, cis-6aβ−12aβ-hydroxyrotenone (7) was evaluated in an in vivo hollow fiber bioassay using HT-29, MCF-7 human breast cancer, and MDA-MB-435 human melanoma cells.

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Level of 3‐Nitropropanoic Acid in Relation to Toxicity of Indigofera spicata in Chicks

Cited by 13 publications

References 0 publications

3-Nitropropionate, the toxic substance of Indigofera , is a suicide inactivator of succinate dehydrogenase

3-Nitropropionate, the toxic substance of Indigofera , is a suicide inactivator of succinate dehydrogenase

Indigofera spicata (creeping indigo) poisoning of three ponies

Bioactive Constituents of Indigofera spicata

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