Metabolic effects of bilirubin removal by polyethylene glycol-bound bilirubin oxidase in icteric rats
Medical Journal of Kinki University 20(2): 201-210
In hepatobiliary diseases accompanied by jaundice, it is not known to what extent the increased bilirubin causes hepatocyte dysfunction. In order to determine whether bilirubin is responsible for the dysfunction, the Polyethylene glycol conjugate of bilirubin oxidase (PEG-BOX), which has a long plasma half-life, was administered to rats with obstructive jaundice (PEG-BOX group), and compared with the control group which was administered polyethylene glycol 5000 alone after bile duct ligation. In the PEG-BOX group, both serum and tissue levels of bilirubin were markedly decreased below those in the control group. The serum level of bile acid in the PEG-BOX group was lower, being associated with its increased urinary excretion than in the control group. No significant difference was observed in hepatic microsomal 7-alpha-hydroxylase activity between the two groups. The serum taurine-conjugated bile acid fraction was higher in the PEG-BOX group than that in the control group. Serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin and total protein were all similar between the two groups. Although the hepatic ATP level and the energy charge of the adenylate pool decreased 3 and 7 days after bile duct ligation, their preservation was higher in the PEG-BOX group than in the control group. In conclusion, lowering of serum and hepatic bilirubin in the bile duct-ligated rats by an application of PEG-BOX resulted in a decrease in the serum bile acid level and increase of urinary excretion of bile acid and thus appears to help retain the liver ATP.