Biphenyldimethyldicarboxylate (BDD), a synthetic compound, in use for the treatment of chronic hepatitis, was studied in a model of cholestatic hepatic injury. Thirty rats with biliary obstruction induced by double ligation and section of the common bile duct were randomly and blindly assigned to receive DDB at four dose levels (3, 15, 75 or 375 mg/kg) or saline (control) once daily orally, starting one day after surgery and continued for one month. Liver damage was evaluated by determining serum levels of liver enzymes and hepatic histopathology. Results indicated that in BDL rats, treatment with DDB resulted in significant increase in alanine aminotransferase (ALT) (49.6-91.2%), alkaline phosphatase (ALP) (24-47.2%), total bilirubin (16.9-18.4%), conjugated bilirubin (37.5-55%), urea (66.7-93.2%) compared with control BDL rats. Glucose levels decreased by 49.6% in BDL rats, but restored to normal values after treatment with DDB. The histological changes in BDL rats were not improved by DDB treatment. It is suggested that in the model of bile duct ligation in rats, the administration of DDB fails to prevent hepatic injury. Results therefore do not indicate a beneficial effect for DDB in the therapy of patients with obstructive jaundice or cholestatic liver disorders. Further studies are needed to explore the exact mechanism of action of DDB.
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