Deleterious Effects of High Concentrations of (-)-Epigallocatechin-3-Gallate and Atorvastatin in Mice With Colon Inflammation

Epigallocatechin-3-gallate (EGCG), atorvastatin (ATST), and their combination have been previously shown to inhibit colon carcinogenesis in animal models. We further investigated their inhibitory activities in azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated Balb/cJ mice and CD-1 mice in 2 slightly different models. The mice were maintained on the AIN93M diet, or a similar diet containing 0.03%, 0.1%, or 0.3% EGCG; 60-ppm ATST; or a combination of 0.1% EGCG and 60-ppm ATST. Unexpectedly, no significant inhibitory activity was observed, and some of the treatment groups resulted in higher tumor multiplicity. To study the effects of EGCG on colon inflammation, CD-1 or C57BL/6 mice were treated with 1.5% DSS for 7 days and sacrificed 3 days later. DSS induced rectal bleeding and colon shortening; treatment with 0.5% EGCG exacerbated the bleeding and decreased mouse body weight. Dietary 0.5% EGCG also increased serum levels of leukotriene B4 and prostaglandin E2. These results suggest that, in mice bearing colon inflammation, high concentrations of EGCG and ATST enhance colon bleeding and may promote colon carcinogenesis.