2010 年 56 巻 1 号 p. 72-80
Poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) is the most common organic germanium compound. This compound has many physiological effects, which are mediated via the modulation of immune-system activation. The intake of dietary Ge-132 causes fecal color changes in humans, and we studied the mechanism of this in a rodent model. Male Wistar rats were given a diet containing 0.05% Ge-132 for two weeks and were compared with rats given a germanium free diet. The color of their feces and cecal contents changed from grayish-green to yellow in rats fed with Ge-132. The concentrations of stercobilin, a major fecal pigment, and total bile acids in cecal contents, were significantly increased by dietary Ge-132. Stercobilin is a metabolite of the bile pigment bilirubin. These results were produced by increases in bile components, such as bilirubin and bile acids, and showed that dietary Ge-132 promotes bile secretion into the intestine. Next, we administered Ge-132 (per os) to male rats at 50 mg/kg body weight per day for four days to reveal its effect on bile (and particularly on bilirubin). Bile juice samples were collected, and their bilirubin content and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity were analyzed. The bilirubin level in the bile was significantly increased by the administration of Ge-132, and the DPPH radical scavenging activity of bile was also significantly increased. As the increases in these two factors were correlated, we supposed that the anti-oxidative properties of the bile of rats fed with Ge-132 were due to bilirubin glucuronides. Oral intake of Ge-132 also increased the mRNA expression of uridine diphosphate glucuronosyltransferase 1a1 (Ugt1a1) and bile acid coenzyme A: amino acid N-acyltransferase (Baat), which encode bile component conjugating enzymes for secretion. The acceleration of bile pigment secretion into the intestine as well as increases in the anti-oxidant activity of bilirubin was induced by oral intake of dietary Ge-132. It is suggested that the antioxidative effect of bile against oxidative stress occurs through radical trapping.