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

By Takashi Nakamura, Taizo Nagura, Mitsuo Akiba, Katsuyuki Sato, Yoshihiko Tokuji, Masao Ohnishi and Kyoichi Osada

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

Poly-trans-[(2-carboxyethyl) germasesquioxane] 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 anti-oxidative effect of bile against oxidative stress occurs through radical trapping. Read more