SOME OBSERVATIONS ON THE MECHANISM OF TOXIC ACTION OF RICIN

¹ University of Chicago Toxicity Laboratory and the Department of Pharmacology, University of Chicago, Chicago, Illinois

1. After receiving an intraperitoneal dose of ricin which produced death in about 24 hours, adult male albino rats showed decreased levels of plasma protein and glucose, with increased concentrations of blood nonprotein nitrogen, lactic acid and urea. The lactate/pyruvate ratio remained constant.

2. The changes in plasma protein and non-protein nitrogen did not occur in adrenalectomized rats maintained on salt. This finding is explained on the basis of loss of gluconeogenetic activity following adrenalectomy.

3. The distribution of the components of the acid-soluble phosphorus fraction of the liver was markedly altered in ricin poisoning. There was a marked loss of adenosine polyphosphates and phosphocreatine, and terminally phosphopyridine nucleotides. The lungs and skeletal muscle showed less striking changes.

4. Slices of livers from poisoned rats failed to use extra oxygen in the presence of fumarate, and failed to show an increased respiration in the presence of dinitrophenol.

5. Assays of homogenates of normal and poisoned rat liver for several enzyme systems showed no difference in activities except for fumarase, which was decreased in poisoned rats to 66 per cent of the normal values.

6. It is suggested that the toxic action of ricin under the conditions employed in these experiments may be explained by an interference with some metabolic process in the liver, possibly in the Krebs cycle.