title: Long-term ursodeoxycholate improves circulating redox changes in primary biliary cirrhotic patients.
abstract: OBJECTIVE
  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 (15-20mg/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 ongoing cholestasis.
authors.affiliation: Clinica Medica A. Murri, Department of Internal Medicine and Public Medicine, University Medical School of Bari, Bari, Italy. i.grattagliano@semeiotica.uniba.it
authors.forename: Ignazio
authors.initials: I
authors.lastname: Grattagliano
authors.forename: Vincenzo O
authors.initials: VO
authors.lastname: Palmieri
authors.forename: Piero
authors.initials: P
authors.lastname: Portincasa
authors.forename: Francesco
authors.initials: F
authors.lastname: Minerva
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palasciano
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002756:Cholagogues and Choleretics / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000097:blood; D008105:Liver Cirrhosis, Biliary / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009603:Nitroso Compounds / Q000097:blood; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013879:Thioredoxins / Q000097:blood; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood; D014580:Ursodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D002756:Cholagogues and Choleretics; D053538:Keratin-18; D009603:Nitroso Compounds; C002744:3-nitrotyrosine; D014443:Tyrosine; D013879:Thioredoxins; D014580:Ursodeoxycholic Acid; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase