Inhibition of rat liver homogenate arginase activity in vitro by the hepatotoxic amino acid indospicine

Madsen, N.P.; Hegarty, M. P.

doi:10.1016/0006-2952(70)90138-3

Cited by 27 publications

(19 citation statements)

References 2 publications

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“… Although the exact pathogenesis of the oral and corneal changes remains undetermined, the microscopic appearance of the oral lesions was less severe, but not dissimilar to that seen with superficial necrolytic dermatitis in dogs and necrolytic migratory erythema in humans, where derangement of amino acid metabolism is thought to be involved . Dogs with superficial necrolytic dermatitis are reported to have mean plasma glutamate or arginine values of less than 20% of those in normal dogs and given that indospicine competitively inhibits arginine incorporation into proteins, it is tempting to speculate that indospicine toxicity may therefore play a role in the pathogenesis of the buccal lesions in horses.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

Indigofera spicata (creeping indigo) poisoning of three ponies

Ossedryver¹,

Baldwin

Stone

et al. 2013

Aust Veterinary J

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“…Further experimental work demonstrated hepatotoxicosis in rats and mice following oral or parenteral administration of purified indospicine 17–19 . Very similar in structure to the essential amino acid arginine, indospicine is not metabolised by arginase and has been shown to competitively block the incorporation of arginine, and subsequently other amino acids, into rat liver protein 18,20,21 . These antimetabolite properties may contribute to the hepatotoxicity of indospicine; however, the exact mechanism of toxicity is yet to be identified 22,23…”

Section: Discussionmentioning

confidence: 99%

“…[17][18][19] Very similar in structure to the essential amino acid arginine, indospicine is not metabolised by arginase and has been shown to competitively block the incorporation of arginine, and subsequently other amino acids, into rat liver protein. 18,20,21 These antimetabolite properties may contribute to the hepatotoxicity of indospicine; however, the exact mechanism of toxicity is yet to be identified. 22,23 Indigofera linnaei (Birdsville indigo) is an Australian native plant source of indospicine that has been implicated in fatal hepatoxicity in dogs fed meat from horses that had grazed the plant.…”

Section: Discussionmentioning

confidence: 99%

Hepatotoxicosis in dogs consuming a diet of camel meat contaminated with indospicine

Fitzgerald

Fletcher²,

Paul

et al. 2011

Aust Veterinary J

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“…Indospicine was concluded to be a competitive antagonist of arginine preventing arginine being incorporated into tRNA as a prelude to ribosomal polypeptide synthesis. Indospicine was also shown to be a competitive inhibitor of rat liver homogenate arginase with the affinity of arginase for indospicine being similar to that of the enzyme for arginine [38]. Inhibition of arginase negatively impacts aminoacylation of arginine and adversely leads to dysfunction of urea cycle.…”

Section: Etiology Of Indospicine Toxicosismentioning

confidence: 99%

The Occurrence and Toxicity of Indospicine to Grazing Animals

2015

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Indospicine is a non-proteinogenic amino acid which occurs in Indigofera species with widespread prevalence in grazing pastures across tropical Africa, Asia, Australia, and the Americas. It accumulates in the tissues of grazing livestock after ingestion of Indigofera. It is a competitive inhibitor of arginase and causes both liver degeneration and abortion. Indospicine hepatoxicity occurs universally across animal species but the degree varies considerably between species, with dogs being particularly sensitive. The magnitude of canine sensitivity is such that ingestion of naturally indospicine-contaminated horse and camel meat has caused secondary poisoning of dogs, raising significant industry concern. Indospicine impacts on the health and production of grazing animals per se has been less widely documented. Livestock grazing Indigofera have a chronic and cumulative exposure to this toxin, with such exposure experimentally shown to induce both hepatotoxicity and embryo-lethal effects in cattle and sheep. In extensive pasture systems, where animals are not closely monitored, the resultant toxicosis may well occur after prolonged exposure but either be undetected, or even if detected not be attributable to a particular cause. Indospicine should be considered as a possible cause of animal poor performance, particularly reduced weight gain or reproductive losses, in pastures where Indigofera are prevalent.

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Inhibition of rat liver homogenate arginase activity in vitro by the hepatotoxic amino acid indospicine

Cited by 27 publications

References 2 publications

Indigofera spicata (creeping indigo) poisoning of three ponies

Indigofera spicata (creeping indigo) poisoning of three ponies

Hepatotoxicosis in dogs consuming a diet of camel meat contaminated with indospicine

The Occurrence and Toxicity of Indospicine to Grazing Animals

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