Long-term ursodeoxycholate improves circulating redox changes in primary biliary cirrhotic patients

Background and aims: Cholestasis is associated with systemic and hepatic oxidative and nitrosative stress; in this scenario, the conjugated hydrophilic bile salt ursodeoxycholate (UDCA) might play a protective role. Methods: Circulating oxidative and nitrosative stress markers were assessed in patients with primary biliary cirrhosis (PBC) before and during UDCA (15-20 mg/kg/day) therapy. Results: In patients with stage I-II PBC, UDCA improved ALT and alkaline phosphatase levels and near normalized serum thioredoxin (1.97 +/- 0.37 vs 2.41 +/- 0.39 nmol/L), nitrotyrosine (15 +/- 4 vs 22 +/- 7 nmol/L), nitrosothiols (144 +/- 28 vs 205 +/- 84 nmol/L) and K-18 levels (162 +/- 21 vs 228 +/- 33 U/L). Conversely, less marked changes were noted in patients with stages III-IV who showed lower thioredoxin (1.01 +/- 0.31 nmol/L), higher nitrosothiols (605 +/- 64 nmol/L), nitrotyrosine (62 +/- 13 nmol/L) and K-18 levels (521 +/- 57 U/L). Overall, thioredoxin was inversely related with nitrotyrosine (r = -0.838, P<0.001) and K-18 (r = -0.838, P<0.001) levels. Nitrosothiols and K-18 were linearly and significantly related with nitrotyrosine (r = 0.862, P<0.001; r = 0.894, P<0.001, respectively). Conclusions: Oxidative and nitrosative changes in patients with PBC are effectively counteracted by UDCA. The protective effect of UDCA, however, are limited to early disease stages and progressively diminishes with on-going cholestasis. (C) 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.