A large number of physiologically functional foods are comprised of plant
polyphenols. Their antioxidative activities have been intensively studied for a long period and proposed to be one of the major mechanisms of action accounting for their health promotional and disease preventive effects.
Green tea polyphenols (GTPs) are considered to possess marked anti-oxidative properties and versatile beneficial functions, including anti-
inflammation and
cancer prevention. On the other hand, some investigators, including us, have uncovered their toxicity at high doses presumably due to pro-oxidative properties. For instance, both experimental animal studies and epidemiological surveys have demonstrated that GTPs may cause hepatotoxicity. We also recently showed that diets containing high doses (0.5-1%) of a
GTP deteriorated
dextran sodium sulfate (DSS)-induced intestinal
inflammation and
carcinogenesis. In addition,
colitis mode mice fed a 1%
GTP exhibited symptoms of nephrotoxicity, as indicated by marked elevation of serum
creatinine level. This diet also increased
thiobarbituric acid-reactive substances, a reliable marker of oxidative damage, in both kidneys and livers even in normal mice, while the expression levels of
antioxidant enzymes and
heat shock proteins (HSPs) were diminished in
colitis and normal mice. Intriguingly, GTPs at 0.01% and 0.1% showed hepato-protective activities, i.e., they significantly suppressed DSS-increased serum
aspartate aminotransferase and
alanine aminotransferase levels. Moreover, those diets remarkably restored DSS-down-regulated expressions of
heme oxygenase-1 and HSP70 in livers and kidneys. Taken together, while low and medium doses of GTPs are beneficial in
colitis model mice, unwanted side-effects occasionally emerge with high doses. This dose-dependent functionality and toxicity of GTPs are in accordance with the concept of hormesis, in which mild, but not severe, stress activates defense systems for adaptation and survival.