Melatonin prevents pigment gallstone formation induced by bile duct ligation in guinea pigs

Free radical-mediated oxidative stress has been implicated in the genesis o f gallstone in vitro, This study was designed to examine the oxidative stre ss changes during pigment gallstone formation and to investigate whether me latonin (MLT) could act as a chemopreventive agent for cholelithiasis in a guinea pig model. The common bile duct of guinea pigs was ligated with or w ithout MLT pretreatment. Animals were studied on day 7, 9, 12, and 14 after surgery. Stone and/or sludge developed in ligated guinea pigs without MLT. Fourier transform infrared spectra of the sludge showed the presence of ca lcium bilirubinate, whose peak height per milligram of sludge gradually inc reased with time after ligation. Total antioxidant activity (TAA) in bile o f guinea pigs at day 14 after ligation reduced to one third of the level in sham-operated controls (P < .001). In addition, the bile of ligated guinea pigs had increased pH (P < .001), bile salts (P < .01), and malondialdehyd e (MDA) (P < .05), compared to sham controls. Pretreatment of guinea pigs w ith MLT at a dose of 1,000 mu g/kg significantly decreased the incidence of pigment gallstone formation at day 14 after ligation, as compared to no pr etreatment (0/7 vs. 8/10). MLT also reverted the ligation-induced changes i n biliary bile salts, pH, MDA, and TAA to control levels. These in vivo fin dings support a causative role of oxidative stress in the bile duct ligatio n-induced pigment gallstone formation. Antioxidants may prove useful in pre venting pigment gallstone formation in humans.