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J.Health Sci., 56(1), 72-80, 2010

Promotive Effects of the Dietary Organic Germanium Poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) on the Secretion and Antioxidative Activity of Bile in Rodents

Takashi Nakamura,*, a, b Taizo Nagura,c Mitsuo Akiba,b Katsuyuki Sato,b Yoshihiko Tokuji,d Masao Ohnishi,a, d and Kyoichi Osadaa, e

aThe United Graduate School of Agricultural Sciences, Iwate University, 3-18-8, Ueda, Morioka, Iwate 020-8550, Japan, bAsai Germanium Research Institute Co., Ltd., 3-131, Suzuranoka-cho, Hakodate, Hokkaido 042-0958, Japan, cNippon Beet Sugar MFG., Co., Ltd., Inada-cho, Obihiro, Hokkaido 080-0831, Japan, dDepartment of Agricultural and Life Science, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan and eDepartment of Agricultural Chemistry, Meiji University, 1-1-1, Higashi-mita, Tama-ku, Kawasaki-shi, Kanagawa 214-8571, Japan

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.