Effect Of Epigallocatechin-3-gallate On The Selenium Toxicity

Selenium is recognized as both an environmental toxicant and an essential nutrientwith the distinction between essentiality and toxicity occurring across a narrow dose rangein mammalian species. These two faces of selenium’s biological activity are dramaticallyaffected by the route of administration and the chemical form of selenium to which anorganism is exposed.Green tea, which is commonly consumed in China, is a rich source of a class offlavonoid compounds referred to as catechins. Green tea catechins are the subject ofextensive investigation owning to their potential health promotion effects and exceptionalabundance in green tea. Accumulated evidence suggests epigallocatechin gallate (EGCG),the predominant component among green tea catechins, is able to prevent certain types ofchronic diseases, including cancer, obesity, type-2diabetes mellitus, lipid metabolismabnormity, atherosclerosis and other cardiovascular diseases. Of particular interest arereports that EGCG can alleviate oxidative damage associated with toxicants.A proof-in-principle experiment was conducted to determine if EGCG wouldameliorate sodium selenite-induce growth suppression. Mice were intraperitioneally (i.p.)injected with sodium selenite once daily for five days at a dose of3mg Se/kg, which fullysuppressed animal growth but in the absence of mortality. Surprisingly theco-administration of the selenite and non-toxic doses of EGCG (10,20and40mg/kg, i.p.)resulted in mortality of treated mice in a dose and time-dependent manner by33.3%,100%and100%, respectively. However, we observed that it not enhanced the seleniumaccumulation by EGCG in acute or short-term experiments. To avoid death and measuredhepatic oxidoreductase, mice (23~25g) were used. Compared to sodium selenite alonetreatment, suppression of liver Catalase activity was significantly greater in the combinedtreatment relative to selenite alone as was the increase in Superoxide dismutase activity;the sodium selenite together with EGCG fully suppressed hepatic glutathione S-transferaseactivity.In this study, EGCG-selenite induced lethality did not result from enhanced seleniumaccumulation but appeared to involve the suppression of a selenite-induced adaptiveresponse as evidenced by hepatic glutathione S-transferase activity. While EGCG has beenreported to ameliorate the toxicity of some agents, the induction of mortality by combinedtreatment with selenite at toxic levels and EGCG at non-toxic levels is a previouslyunrecognized synergism that must be considered not only in the remediation of environmental exposures but also in the development of pharmaceuticals andnutriceuticals.