SEQUENTIAL-CHANGES OF ENERGY-CHARGE, LIPOPEROXIDE LEVEL, AND DNA-SYNTHESIS RATE OF THE LIVER FOLLOWING BILIARY OBSTRUCTION IN RATS

To clarify the effects of obstructive jaundice on the liver, sequentia l changes of hepatic energy charge, the concentrations of adenine nucl eotides and malondialdehyde, DNA synthesis rate, and histology of the liver were examined on the day before and Days 1, 2, 4, 7, and 14 afte r biliary obstruction in rats and compared with those of sham-operated controls. Foci of necrotic hepatocytes were present on Days 1 and 2 a nd mitoses of the hepatocytes were frequently observed with a peak on Day 2 in the jaundiced liver. Marked proliferation of bile ductules we re subsequently observed on Days 7 and 14, resembling biliary cirrhosi s. The DNA synthesis rate was significantly activated after bile duct obstruction with its peak on Day 2, more than nine times higher than t he 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 g radually increased and became significantly higher on Day 14. We concl ude that obstructive jaundice decreases hepatic energy charge and incr eases the lipoperoxide level. In the initial stage of obstructive jaun dice, the hepatocytes proliferate associated with activated DNA synthe sis probably to compensate hepatic damage; however, prolonged obstruct ive jaundice induces functional hepatic injury possibly necessitating biliary drainage. (C) 1996 Academic Press, Inc.