Gallstone disease: Free radical reactions and the ambivalent role of bilirubin in the pathomechanism of gallstone formation

Abstract

In the formation of gallstone diseases, there are numerous genes, that are held responsible for liver disorders primarily and diseases of bile flow and bile formation, modification of lipid metabolism diabetes mellitus, obesity, glutene sensitive enteropathy, Crohn-disease, Down syndrome, Gucher syndrome, cystic fibrosis as well as haematological disorders and state following ileum resection. In the development of these, bacterial infections, inflammatory reactions, metal element power and free radicals play an important role. Fatty acids, lipid oxides, diene conjugates and other lipid peroxidation products are moving from the liver to the bile, and they initiate primer and secondary free radical reactions in the bile duct and gallbladder. The inflammation processes in the gallbladder wall produce free radicals. The free bilirubin content of the bile behaves pro- and antioxidant molecules. The ambivalent property of free bilirubin, which is detected concentration in the gallbladder bile -- from microsomal leakage or as a consequence of bacterial deglucuronidation -- increases the free radical reactions in the gallbladder. The gallstone formation of free bilirubin with metal ions, primarily Ca ++ ions makes calcium hydrogen bilirubinate in the bile. Calcium ions can react with fatty acids and hereby modify the bile viscosity. The lipids, free bilirubin and metal elements are all components in stone formation. Antioxidants, concerning their derivates or molecules, medicines, which increase antioxidant property can influence the bile composition or inhibit the gallstone formation on several levels.