Addition of N-acetylcysteine to aqueous model bile systems accelerates dissolution of cholesterol gallstones.

The organic matrix of cholesterol gallstones contains a macromolecular complex of mucin and bilirubin that may inhibit stone dissolution by limiting contact of desaturated bile with crystalline cholesterol. The goal of this study was to determine if the mucolytic agent N-acetylcysteine could accelerate gallstone dissolution in vitro. Paired gallstones were dissolved in either pure taurocholate (140 mM) or ursodeoxycholate (100 mM), or in bovine bile supplemented with either taurocholate or ursodeoxycholate to achieve the same respective bile-salt concentrations. N-acetylcysteine was added to 1 stone from each pair at a concentration of 500 mM in pure bile salts and 100 mM in supplemented bile. Gallstones dissolved significantly faster in bovine bile supplemented with taurocholate or ursodeoxycholate than in pure solutions of the respective bile salts (n = 30, p less than 0.001). N-acetylcysteine significantly accelerated gallstone dissolution in pure solutions of bile acids (n = 30, p less than 0.001 for each) and in supplemented bovine biles (n = 30, p less than 0.001). N-acetylcysteine also significantly increased the frequency of complete gallstone dissolution in taurocholate-supplemented (66.6% vs. 40.0%) and ursodeoxycholate-supplemented (76.6% vs. 50.0%) bile. These results indicate that the mucolytic agent N-acetylcysteine significantly accelerates in vitro gallstone dissolution. We speculate that adjuvant therapy with an appropriate mucolytic agent may potentially increase the efficacy of clinical gallstone dissolution.