Ursodeoxycholic acid suppresses extent of lipid peroxidation in diseased liver in experimental cholestatic liver disease

The therapeutic benefit of ursodeoxycholic acid (UDCA) in treating cholesta tic liver disease is globally recognized. It is generally accepted that the mechanism of action of UDCA can be attributed to several diverse processes that appear to be uniformly targeted towards minimizing the deleterious ac tions of accumulated hydrophobic bile acids in the cholestatic liver. Since hydrophobic bile acids are prooxidants, emerging in vitro evidence suggest s that UDCA may have an antioxidant mechanism of action. We hypothesize tha t UDCA suppresses the extent of lipid peroxidation in the cholestatic liver . This hypothesis was tested by assessing the extent of lipid peroxidation in livers harvested from chronic bile duct ligated (CBDL) rats dosed daily for 24 days with 5, 10, or 15 mg/kg UDCA. The extent of lipid peroxidation was evaluated by determining the hepatic content of conjugated dienes, lipi d peroxides, and malondialdehyde. The data were compared with identical dat a collected from unoperated control and 24-day bile duct manipulated (SO) r ats. In the two groups of control rats, UDCA has no effect on the serum ind ices of liver function. In CBDL rats, UDCA suppressed the increased extent of lipid peroxidation in the liver in a dose-dependent manner in the absenc e of improvement of laboratory parameters of liver function and hepatic arc hitecture. In conclusion, UDCA suppresses the augmented extent of lipid per oxidation in the diseased liver of CBDL rats.