The Occurrence and Toxicity of Indospicine to Grazing Animals

Abstract

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.

Synthesis of l-indospicine, [5,5,6-2H3]-l-indospicine and l-norindospicine

“…1) is an unusual amino acid which occurs only in members of the Indigofera genus with about 700 species of this genus distributed across tropical Africa, Asia, Australia and North and South America. 2 The toxicological symptoms were found to be identical to those found in rats orally dosed with indospicine 3 and it was concluded that indospicine in Indigofera spp. that contain this non-proteogenic amino acid and also in secondary (carnivore) consumers of meat from these herbivores.…”

“…2 The toxicological symptoms were found to be identical to those found in rats orally dosed with indospicine 3 and it was concluded that indospicine in Indigofera spp. 1,10 Indospicine is structurally analogous to arginine (2), possessing an amidine function rather than a guanidine, and as an arginine antagonist competes with arginine for the active site of arginase and competitively blocks incorporation of arginine into protein with consequential inhibition of protein and DNA synthesis. Although this amino acid is commonly associated with liver toxicity, the embryotoxicity and teratogenicity of indospicine, 4 as well as its ability to inhibit nitric oxide synthase 5 have also been examined.…”

Building a botanical foundation for perennial agriculture: Global inventory of wild, perennial herbaceous Fabaceae species

“…"Toxicity -lab animal" described 184 species reported as toxic in studies in which small animals in confinement were overfed 185 quantities of a plant or plant extract, since results of such studies are not always relevant to 186 normal exposure. "Toxicity -predicted" was used to flag species without reports of illness, but 7 that had been reported in survey studies to contain chemicals similar to other toxic species (in 188 particular, Davis, 1982;Williams & Gómez-Sosa, 1986;Wink, Meisner, & Witte, 1995;189 Fletcher, Al Jassim, & Cawdell- Smith, 2015). Generally, we observed that species whose 190 chemistry and bioactivity are understudied should similarly be suspected of toxicity when 191 toxicity is common within the same genus.…”

Building a botanical foundation for perennial agriculture: Global inventory of wild, perennial herbaceous Fabaceae species

“…“Toxicity—lab animal” described species reported as toxic in studies in which small animals in confinement were overfed quantities of a plant or plant extract, since results of such studies are not always relevant to normal exposure. “Toxicity—predicted” was used to flag species without reports of illness, but that had been reported in survey studies to contain chemicals similar to other toxic species (in particular, Davis, ; Fletcher, Al Jassim, & Cawdell‐Smith, ; Williams & Gómez‐Sosa, ; Wink, Meisner, & Witte, ). Generally, we observed that species whose chemistry and bioactivity are understudied should similarly be suspected of toxicity when toxicity is common within the same genus.…”

“…"Toxicity-predicted" was used to flag species without reports of illness, but that had been reported in survey studies to contain chemicals similar to other toxic species (in particular, Davis, 1982;Fletcher, Al Jassim, & Cawdell-Smith, 2015;Williams & Gómez-Sosa, 1986;Wink, Meisner, & Witte, 1995). Generally, we observed that species whose chemistry and bioactivity are understudied should similarly be suspected of toxicity when toxicity is common within the same genus.…”