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Supplement: Significance of Garlic and Its Constituents in Cancer and Cardiovascular Disease

Aged Garlic Extract Inhibits Development of Putative Preneoplastic Lesions in Rat Hepatocarcinogenesis^1,2

Naoto Uda^*,3, Naoki Kashimoto^*, Isao Sumioka^*, Eikai Kyo^*, Shin-ichiro Sumi^* and Shoji Fukushima

^* Healthcare Research Institute, Wakunaga Pharmaceutical Co., Ltd., Hiroshima 739-1195, Japan and First Department of Pathology, Osaka City University Medical School, Osaka 545-8585, Japan

³ To whom correspondence should be addressed. E-mail: uda_n{at}wakunaga.co.jp.

A unique garlic preparation, aged garlic extract (AGE), was examined for its modifying effect on diethylnitrosamine (DEN)-induced neoplasia of the liver in male F344 rats, using the medium-term bioassay system based on the 2-step model of hepatocarcinogenesis. Carcinogenic potential was scored by comparing the numbers and areas of induced glutathione S-transferase placental form (GST-P)-positive hepatocellular foci. GST-P-positive foci were significantly decreased in rats treated with AGE at doses of 2, 5, and 10 mL/kg, i.g., 5 times per week during the promotion phase. In addition, to clarify the mechanism underlying the inhibitory effect of AGE, the effect of AGE on hepatocellular proliferation was evaluated using partially hepatectomized rats as a liver-regeneration model. The bromodeoxyuridine-labeling indices in the livers of the AGE group were significantly lower than those in the control group at 24 h, the maximum proliferation period after partial hepatectomy. These findings indicate that AGE inhibited the development of putative preneoplastic lesions in rat hepatocarcinogenesis, involving a slowing in the proliferation rate of liver cells after partial hepatectomy.

KEY WORDS: • hepatocarcinogenesis • aged garlic extract • chemoprevention • medium-term bioassay system • glutathione S-transferase