Polyethylene glycol-modified bilirubin oxidase improves hepatic energy charge and urinary prostaglandin levels in rats with obstructive jaundice.
OBJECTIVE
No study has so far been conducted to clarify whether the presence of hyperbilirubinemia is detrimental to liver and renal functions. In the present study, the effects of polyethylene glycol-modified bilirubin oxidase (PEG-BOX) therapy on liver and renal function tests, hepatic energy charge and urinary prostaglandin levels were evaluated in a rat model of obstructive jaundice.


METHODS
Sprague-Dawley rats were used in the experimental model of obstructive jaundice. PEG-BOX or an equivalent amount of PEG alone was intravenously injected into the animals and sampling of blood and urine, and liver harvesting were done sequentially after bile duct ligation.


RESULTS
Conventional liver function tests showed no difference between PEG-BOX and control groups. However, bilirubin concentrations in the peripheral blood and liver tissue specimens markedly decreased, and the hepatic energy charge significantly increased in the PEG-BOX group as compared to controls. The blood concentration of bile acid was lower, but its urinary excretion was higher in the PEG-BOX group than in the control group. In vitro incubation of PEG-BOX with serum from rats with obstructive jaundice decreased the concentration of bilirubin but not that of bile acid. The urinary levels of prostaglandin E2 and the thromboxane B2/6-keto-prostaglandin Fla ratio were significantly lower in the PEG-BOX group than in the control group.


CONCLUSIONS
The systemic reduction of bilirubin concentration may contribute to normalization of the urinary levels of prostaglandins and thromboxane B2, to decrease in serum bile acid levels, and to improvement of the hepatic energy charge in obstructive jaundice. These findings suggest that preoperative improvement of jaundice may be beneficial to patients with obstructive jaundice.
Kamisako
T
T
Second Department of Internal Medicine, Kinki University School of Medicine, Osakayama, Japan.
Miyawaki
S
S
Gabazza
E C
EC
Ishihara
T
T
Kamei
A
A
Kawamura
N
N
Adachi
Y
Y
D000818:Animals; D002779:Cholestasis / Q000188:drug therapy* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004734:Energy Metabolism / Q000187:drug effects*; D006530:Hepatorenal Syndrome / Q000503:physiopathology; D006932:Hyperbilirubinemia / Q000503:physiopathology; D008099:Liver / Q000187:drug effects*; D008297:Male; D010088:Oxidoreductases / Q000737:chemistry / Q000627:therapeutic use*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011092:Polyethylene Glycols / Q000737:chemistry*; D011453:Prostaglandins / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley
D011453:Prostaglandins; D011092:Polyethylene Glycols; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C042401:bilirubin oxidase