Green tea polyphenol administration partly ameliorates chemotherapy-induced side effects in the small intestine of mice.
The chemotherapeutic agent irinotecan (IT) is highly effective against several types of cancer, although its use is limited due to severe intestinal toxicity. The aim of this study was to evaluate inflammatory and oxidative stress-related processes contributing to small intestinal mucosa damage and to determine the extent to which green tea polyphenols could ameliorate the detrimental effects induced by IT. In Expt. 1, mice were challenged intraperitoneally with IT or saline on 2 consecutive days. For time kinetic measurements, the IT-treated mice were killed at 3, 24, 48, 72, and 96 h after the 2nd dose of IT. Three hours after IT administration, the ileum glutathione concentration dropped significantly. Lipid peroxidation and inflammation, as measured by macrophage inflammatory protein-2 content, myeloperoxidase activity, and nuclear factor-kappaB translocation, were highest between 24 and 48 h after IT treatment. In Expt. 2, green tea polyphenols (1 g/L) were supplied via drinking water for 7 d before and 3 d after treatment with IT. Green tea polyphenols significantly affected the glutathione:glutathione disulfide ratio but not lipid peroxidation, macrophage inflammatory protein-2 levels, myeloperoxidase activity, or nuclear factor-kappaB activation. Our study reveals that IT administration is associated with oxidative stress and inflammation, both occurring simultaneously to IT-induced mucosal damage. The antioxidative defense is affected soon after IT administration. Green tea polyphenols supplied orally protected against oxidation in our experimental model and could be one approach to reducing the risk of IT-induced side effects in the clinical setting.
Wessner
Barbara
B
Department of Surgery, Research Laboratories, Medical University of Vienna, A-1090 Vienna, Austria. barbara.wessner@meduniwien.ac.at
Strasser
Eva-Maria
EM
Koitz
Nina
N
Schmuckenschlager
Claudia
C
Unger-Manhart
Nicole
N
Roth
Erich
E
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000633:toxicity*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000077146:Irinotecan; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000008:administration & dosage*; D059808:Polyphenols; D013662:Tea / Q000737:chemistry*
D000970:Antineoplastic Agents; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D000077146:Irinotecan; D002166:Camptothecin