The role of ursodeoxycholic acid in bile acid-mediated kidney fragment toxicity

Abstract

Elevated levels of bile acids are thought to play an important role in the renal failure of patients with obstructive jaundice undergoing surgery. In contrast, ursodeoxycholic acid (UDA) is widely used to improve cholestasis and has been proposed as protective bile acids and antioxidant. The present study employs kidney fragments to determine the role of reactive oxygen species (ROS) in the mechanism of toxicity of hydrophobic bile acids and to determine the nephroprotectant properties of UDA against the hydrophobic bile acids. The hydrophobic bile acids chenodeoxycholic (200 microM) and deoxycholic acid (200 microM) significantly (P<0.05) increased lactate dehydrogenase leakage (LDH) from glomerular fragments from 2.7+/-0.4 to 5.03+/-0.23 and 4.66+/-0.37 (micromol NADH consumed/min/mg protein) for chenodeoxycholic and deoxycholic acid respectively. Preincubating the fragments with UDA (500 microM) did not prevent the leakage of LDH caused by the bile acids. The level of lipid peroxidation was not increased in fragments exposed to either ursodeoxycholic (0-500 microM), lithocholic (0-100 microM), chenodeoxycholic (0-500 microM) or deoxycholic acid (0-500 microM). Furthermore UDA (500 microM) did not prevent the increase in lipid peroxidation caused by tert-butyl hydroperoxide (0-1000 microM) in the fragments. These results suggest that hydrophobic bile acids do not cause lipid peroxidation in kidney fragments and that UDA is neither capable of preventing the loss of membrane integrity induced by hydrophobic bile acids or acting as an antioxidant in kidney fragments.