Acute biochemical changes in rat liver induced by the naturally occurring amino acid indospicine

Christie, G.S.; Madsen, N.P.; Hegarty, M. P.

doi:10.1016/0006-2952(69)90039-2

Cited by 27 publications

(15 citation statements)

References 9 publications

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“…10,15,16 Further experimental work demonstrated hepatotoxicosis in rats and mice following oral or parenteral administration of purified indospicine. [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.…”

Section: Discussionmentioning

confidence: 99%

“…An additional 15 dogs (dogs [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] were identified from clinical records as having also eaten the diet and their serum biochemistry (ALP, ALT, cholesterol and albumin) was determined. Dogs 5,7,8,11,12,15 and 19 had ceased the diet between 4 and 13 days before blood samples were collected ( Table 1).…”

Section: Other Dogs Exposed To the Camel Meat Dietmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Other Dogs Exposed To the Camel Meat Dietmentioning

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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“…Subcutaneous injection of indospicine into mice produced fat accumulation and cytological changes in the liver, which was inhibited by simultaneous injection of arginine [4]. In in vivo rat studies, oral dosing caused a pronounced inhibition of incorporation of 14 C-leucine into hepatic and serum protein, with this inhibition of protein synthesis then followed by a marked rise in the level of liver triglycerides [36]. Incorporation of 14 C-arginine into protein was depressed in cell-free fractions from the livers of rats treated with indospicine and also on addition of indospicine in vitro [37].…”

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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“…Due to the evident structural similarity, indospicine has the potential to interfere with a range of mammalian arginine metabolic pathways, and has been demonstrated experimentally to cause both liver degeneration (Hegarty and Pound, 1970) and also teratogenic and embryo-lethal effects (Pearn and Hegarty, 1970). It has been shown to interfere with hepatic protein metabolism, producing fat accumulation and cytological changes in the liver (Christie et al, 1969;Christie et al, 1975). Indospicine is unusual in that it accumulates as the free amino acid in body tissues of livestock consuming these legumes.…”

Section: Introductionmentioning

confidence: 99%

Assessing the risk of residues of the toxin indospicine in bovine muscle and liver from north-west Australia

Netzel

Palmer

Masters

et al. 2019

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Indospicine is a natural toxin occurring only in Indigofera plant species, including the Australian native species I. linnaei. These perennial legumes are resistant to drought and palatable to grazing livestock including cattle. Indospicine accumulates in the tissues (including muscle) of animals grazing Indigofera and these residues persist for several months after exposure. Dogs are particularly sensitive to indospicine with reports in past decades of hepatotoxicosis and mortalities in dogs after dietary exposure to indospicinecontaminated horse and camel meat. The risk for human consumption is not known, and the current study was undertaken to assess indospicine levels in cattle going to slaughter from divergent regions of Western Australia, and to predict the likelihood of significant residues being present. Muscle and corresponding liver samples from 776 cattle originating from the Kimberley and Pilbara Regions in the tropical north of the state, where I. linnaei is prevalent, and 640 cattle from the South West and South Coast Regions in the temperate south west of the state, where the plant is not known to occur, were collected at abattoirs over four seasons in 2015-2017. Indospicine levels were measured by LC-MS/MS and ranged from below detection to 3.63 mg/kg. No indospicine residues were detected in any of the animals originating from the South West and South Coast Regions. Prevalence of indospicine residues in cattle from the Kimberley Region was as high as 33% in spring and 90% in autumn, with positive animals being present in most consignments and on most properties. The average prevalence of indospicine residues from the Kimberley and Pilbara Regions throughout the survey period was 62%. @Risk best fit probability distributions showed ninety-fifth percentile (P95) indospicine concentrations of 0.54 mg/kg for muscle and 0.77 mg/kg for liver in cattle originating from the Kimberley and Pilbara Regions during the survey period. When considered with average Australian meat consumption data, the 15 or more animals. Consignments were designated as 'spring' for slaughter dates within the period 1 August to 30 November and 'autumn' for 1 March to 31 July. No consignments were sampled December to February as this period represents the rainy season in the Kimberley and Pilbara Regions, and for logistical reasons animals are not sent to abattoir during this period.

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Acute biochemical changes in rat liver induced by the naturally occurring amino acid indospicine

Cited by 27 publications

References 9 publications

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

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

The Occurrence and Toxicity of Indospicine to Grazing Animals

Assessing the risk of residues of the toxin indospicine in bovine muscle and liver from north-west Australia

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