High physiological levels of melatonin in the bile of mammals

Bile is an important physiological bodily fluid which functions in the regulation of cholesterol metabolism, promotes the absorption of lipid and fat-soluble vitamins by the gut and serves in the excretion of toxic substances from the liver. Conversely, due to autooxidative processes bile is highly toxic to the hepatocyte and gastrointestinal epithelium. In this investigation, extremely high day time physiological levels of the endogenous antioxidant, melatonin, were measured in the bile of several mammals including rat, guinea pig, rabbit, pig, monkey and humans. Melatonin concentrations in the bile samples ranged from 2,000 to 11,000 pg/ml when measured by radioimmunoassay (RIA). These melatonin levels in bile are 2 to 3 orders of magnitude higher than those in day time serum. The presence of melatonin in bile was confirmed by HPLC with an electrochemical detector. This method, like the RIA, also documented very high levels of melatonin in bile. The presence of high levels of melatonin in bile may be essential to prevent oxidative damage to biliary and small intestinal epithelium induced by bile acids and oxidized cholesterol derivatives.