Studies on digoxin--14C-acetate incorporation in to digoxin and degenerative changes in the brain in rats administered digoxin.

The human hypothalamus produces an endogenous membrane Na+-K+ ATPase inhibitor digoxin. Digoxin is a steroidal glycoside and could be synthesised by the isoprenoid pathway. The other metabolites of the isoprenoid pathway are cholesterol, dolichol and ubiquinone. We have tried to find out the extent of incorporation of 14C acetate into digoxin in rat brain. The effects of digoxin administration on the rat brain was also studied. The results show that the percentage incorporation of 14C acetate into digoxin is low but detectable. The maximum incorporation was observed for cholesterol, followed by dolichol and finally ubiquinone. The histopathological changes observed after digoxin administration were focal degeneration of the ganglion cells in the cerebrum and cerebellum. The carbohydrate components of the glycoproteins were reduced and the concentration of serotonin, dopamine, and epinephrine showed a significant increase. The role of digoxin in mediating neuronal cell death is discussed.