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Green Tea Polyphenol Administration Partly Ameliorates Chemotherapy-Induced Side Effects in the Small Intestine of Mice

Abstract

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-κB 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-κB 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. J. Nutr. 137: 634-640,
2007.

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