Circadian rhythm of hepatocellular structures in rats dosed phenobarbital

The circadian rhythm of liver weight and hepatic structures was studied in rats given a maximum tolerated dose of 70 or 80 mg/kg/day Phenobarbital during 7 days and killed at four different hours of the following day. The drug-induced increase in liver weight in % of body weight of rats was about 1% in the morning and in the afternoon in comparison with controls. At 6.00--7.00 during the glycogen maximum, the fine structure of hepatocytes was normal except enlargement and glycogen depletion of cells in the near neighbourhood of central veins. From 9.00--10.00 the mitotic activity was markidly increased and parallel to the progressive disappearance of glycogen the smooth endoplasmic reticulum (SER) became prominent. Hypertrophy of SER was fully developed at 15.00--16.00 and 17.00--18.00.