Sequential Changes of Energy Charge, Lipoperoxide Level, and DNA Synthesis Rate of the Liver Following Biliary Obstruction in Rats

Abstract

To clarify the effects of obstructive jaundice on the liver, sequential changes of hepatic energy charge, the concentrations of adenine nucleotides and malondialdehyde, DNA synthesis rate, and histology of the liver were examined on the day before and Days 1, 2, 4, 7, and 14 after biliary obstruction in rats and compared with those of sham-operated controls. Foci of necrotic hepatocytes were present on Days 1 and 2 and mitoses of the hepatocytes were frequently observed with a peak on Day 2 in the jaundiced liver. Marked proliferation of bile ductules were subsequently observed on Days 7 and 14, resembling biliary cirrhosis. The DNA synthesis rate was significantly activated after bile duct obstruction with its peak on Day 2, more than nine times higher than the control value and returned to the control level on Day 14. Hepatic ATP concentration and energy charge gradually declined with prolonged jaundice and significantly lower levels persisted after Day 7 compared with the controls. The malondialdehyde level in the jaundiced liver gradually increased and became significantly higher on Day 14. We conclude that obstructive jaundice decreases hepatic energy charge and increases the lipoperoxide level. In the initial stage of obstructive jaundice, the hepatocytes proliferate associated with activated DNA synthesis probably to compensate hepatic damage; however, prolonged obstructive jaundice induces functional hepatic injury possibly necessitating biliary drainage.