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.
Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA.
Fei
F
Guan
Anna B
AB
Liu
Guangxun
G
Li
Zhihong
Z
Yang
Yuhai
Y
Sun
Chung S
CS
Yang
Jihyeung
J
Ju
D000818:Animals; D000069059:Atorvastatin; D001397:Azoxymethane / Q000633:toxicity; D002392:Catechin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003092:Colitis / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000188:drug therapy / Q000209:etiology; D016264:Dextran Sulfate / Q000633:toxicity; D015232:Dinoprostone / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000209:etiology; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000009:adverse effects*; D007975:Leukotriene B4 / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects*; D012007:Rectum / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects
D006538:Heptanoic Acids; D011758:Pyrroles; D007975:Leukotriene B4; D002392:Catechin; D016264:Dextran Sulfate; D000069059:Atorvastatin; C045651:epigallocatechin gallate; D015232:Dinoprostone; D001397:Azoxymethane