Effects on the liver in the rat of ingestion of Indigofera spicata, a legume containing an inhibitor of arginine metabolism.

The non-protein amino acid indospicine, which occurs in the free state in high concentration in the tropical pasture legume Indigofera spicata, causes toxic liver lesions in ruminants. Indospicine is a specific antagonist of arginine and an inhibitor of protein synthesis. The liver lesion was studied in rats at four dose levels by feeding diets containing 96, 48, 24 and 15 per cent. of the seed. The too higher levels caused death of most animals in 2-6 wk. Females were more susceptible than males. The rats fed the 24 per cent. seed diet developed a nodular cirrhosis by 6 wk and survived up to 18 wk. The rats fed the 15 per cent. seed diet developed cirrhosis at 16 wk and survived up to 28 wk. Prior to the onset of cirrhosis the liver showed a characteristic lesion consisting of hepatomegaly, periportal fatty change, portal cellularity due to proliferation of ovoid and cuboidal duct cells, gross enlargement of the hepatocyte cytoplasm nuclei and nucleoli in spite of brisk mitotic activity, and focal centrilobular necrosis. The lesion was interpreted as a restricted hepatic response to a growth stimulus, possibly the mobilisation of tissue amino acids. Improvement occurred in the rats fed the two lower dosage levels after nodular cirrhosis developed, producing a new parenchyma. An attempt is made to relate the lesions to the biochemical derangement induced by a specific amino acid antagonist.