Relationship between bilirubin free radical and formation of pigment gallstone.
In this paper, we summarize the main progresses made in our group in the field of the mechanism of pigment gallstone formation. It was found that after treatment with free radicals, bilirubin (BR) was changed into free radical itself, and a semiquinone free radical and a superoxide free radical bound with metal were recognized, which was detected by ESR (electron spin resonance). By the means of NMR (nuclear magnetic resonance) and IR (Infra-red spectra), it was postulated that bilirubin polymerized through the reaction between the vinyl group and the hydroxyl group under the attack of free radicals. It was also found that bilirubin free radical were liable to calcify in a kinetic study. Because of its chemical properties, bilirubin free radical was shown to be cytotoxic to hepatocyte, which was demonstrated based on the following facts: induction of phospholipid peroxidation (LPO), leakage of lactate dehydrogenase (LDH) and decrease of glutathione. As to the mechanism of bilirubin-induced cytotoxicity, it was postulated that the main target of bilirubin free radical was the cell membrane, including phospholipid and membrane bound proteins, especially spectrin, a content of cytoskeleton. Based on the results mentioned above, it was deduced that bilirubin free radical is the key factor that initiates and promotes the formation of pigment gallstone, which is consistent with other researches in recent years.
Liu
Xiang-Tao
XT
Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China. lxt421@sohu.com
Hu
Jian
J
D001663:Bilirubin / Q000737:chemistry / Q000378:metabolism*; D002769:Cholelithiasis / Q000209:etiology* / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D010860:Pigments, Biological / Q000378:metabolism
D005609:Free Radicals; D010860:Pigments, Biological; D001663:Bilirubin