Toxic effects of ricin: studies on the pathogenesis of liver lesions.

Rats treated with ricin, an inhibitor of protein synthesis, at the dose of 1 mug/100 g body weight, developed within 72 hours a severe liver necrosis. Protein synthesis was practically unchanged. The ultrastructural changes that ricin induces in rat liver were investigated. The earliest changes were observed in sinusoidal cells which were progressively damaged until they became necrotic. Only after the development of these lesions hepatocytes appeared to be damaged. The hypothesis is formulated that hepatocyte necrosis is a consequence of the disappearance of sinusoidal cells. This might explain why protein synthesis was unaffected in liver: since ricin exerted its toxic effect on the sinusoidal cells the inhibition was not detectable, these cells being "diluted" by the mass of parenchymal cells. Ricin at the dose of 10 mug/100 g body weight did not affect protein synthesis in the liver, but exerted a marked and precocious inhibition of protein synthesis in the spleen, which is very rich in reticuloendothelial cells. Moreover, a severe necrosis of the red pulp of the spleen was observed in rats poisoned with this dose of ricin.