Ultrastructural and functional effects of therapeutic dose of digoxin on rat hepatic cells

Male Sprague Dawley rats weighing 250 to 300 g were injected with digoxin 0.03 mg/kg i.p. twice a day at 12 hr intervals for 5 days. Ultrastructural studies of the liver showed marked hypertrophy of the smooth endoplasmic reticulum (up to 3 times normal) large and dispersed nucleolus and significant glycogen accumulation. Functionally, a nonspecific response of microsomal drug metabolizing enzymes (increased activity of N demethylation of dimethylaniline and p hydroxylation of aniline) was found, but this response was of very short duration. It is suggested that the differences in toxic and therapeutic doses of digoxin account for the variability of effects of this glycoside in clinical practice.