Effects of green tea polyphenols on dextran sulfate sodium-induced colitis in male ICR mice Free

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Green tea polyphenols (GTP) have been shown to induce apoptosis in various cancer cells and prevent experimental carcinogenesis in many animal models. Further, the results of some epidemiological surveys have suggested that green tea consumption has an inverse association with cancer incidence in humans, though Hirose et al. reported that GTP enhanced colon carcinogenesis in rat models (1, 2). Along a similar line, we recently demonstrated that (-)-epigallocatechin gallate (EGCG), the major constituent of green tea, enhances the production of pro-matrix metalloproteinase (pro-MMP)-7 by HT-29 cells via a pro-oxidative mechanism (3). Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) of unknown cause, which may progress to colorectal cancer in chronic and prolonged cases. Dextran sulfate sodium (DSS)-induced experimental colitis animal models are known to exhibit many symptoms similar to those seen in human UC, e.g., diarrhea, bloody feces, weight loss, and colorectal shortening. In the present study, we examined the effects of oral feeding of GTP (35% EGCG, 70% catechins, 3% caffeine) on DSS-induced colitis in male ICR mice. After a 1-week quarantine, control mice were given tap water and a basal diet ad libitum for 6 days, while those in the DSS group were given 2% (w/v) DSS in tap water and basal diet. And GTP (0.1%, 0.5%, or 1%) was added to the basal diet concurrently with DSS treatment. In addition, 1% GTP was added to the basal diet without DSS for the GTP alone group. After 6 days, the liver, kidneys, colon, and spleen were excised from each mouse in all groups, and their weights or lengths were measured. In addition, the levels of proinflammatory cytokines in colonic mucosa were quantified. Mice in the 0.5% and 1% GTP groups exhibited diarrhea or bloody feces more severe than those in the DSS group. Further, body weights in the 1% GTP group as well as colorectal lengths in both the 0.5% and 1% groups were reduced as compared to those in the DSS group, while the weight of the spleen in the 1% GTP group was increased as compared to that in the DSS group. Notably, we also saw a marked increase in interleukin (IL)-1β and IL-6 levels in the 0.5% and 1% groups as compared with the DSS group, whereas 0.1% GTP suppressed IL-1β, but not IL-6, production. In addition, DSS treatment led to a notable increase in macrophage migration inhibitory factor as compared with the control group, in contrast to its substantial attenuation by 0.1% GTP, while neither 0.5% or 1% GTP had any effect. The symptomatic and biochemical data for the GTP alone group were nearly identical to those in the control group, suggesting that the 1% GTP diet without DSS treatment did not have a proinflammatory effect on the colorectum. Together, our results indicate that the effects of GTP on DSS-induced colitis are dependent on GTP dosage. References: (1) Hirose et el., Cancer Lett., 168, 23-9, 2001, (2) ibid, 188, 163-70, 2002, (3) Kim et al., Carcinogenesis, 26, 1553-62, 2005.