OBJECTIVEPhytoestrogen isoflavones (IFs) are considered to suppress estrogen-related cancers through their antiestrogenic activity. The antioxidant effect of IFs, however, has not been confirmed in anin vivo system, so suppression of hydroperoxide formation and resultant DNA adduct formation were studied.

METHODSThe antioxidant effects of the soya-hypocotyl tea (SHT), which contained daidzein (14+/-1.5 mg/l) and genistein (3+/-0.5 mg/l), were examined in Wistar rats fed the AIN-76 control diet or iron deficient diet (FeD) for 4 weeks. The intake amount of the diet and IFs were measured daily. Urinary excretion of IFs was measured for 3 days before sacrifice. In addition to the serum lipid analyses, phosphatidylcholine hydroperoxide (PCOOH), and phosphatidylethanolamine hydroperoxide (PEOOH) production in red blood cells and the liver were measured as a biomarker of oxidants. Production of DNA adducts by oxidative stress was measured by the amount of 8-hydroxy-2'-deoxyguanosine (oh(8)dG) in the liver and kidney, and urine. Histological changes were checked by H&E staining and immunohistochemistry for oh(8)dG.

RESULTSFeD rats showed anemia, growth retardation, hyperlipidemia. IFs only lowered the triacylglycerol level and did not change the cholesterol level. Rats fed the normal diet did not show suppression of PCOOH and PEOOH production in either red blood cells or the liver, while groups administered SHT showed suppressed production of PCOOH and PEOOH in the liver. The cumulative intake of daidzein, genistein and the total amount of IFs showed significant inverse associations with urinary excretion of oh(8)dG. oh(8)dG in the kidney showed an inverse association with the amount of oh(8)dG in the urine. Enzymehistochemically, a strong localization of oh(8)dG was found in the epithelial cells of the bile canaliculi and proximal tubules of the kidney.

CONCLUSIONIFs and SHT showed antioxidant effects at physiological concentrations in anin vivo system. The antioxidant effects of IFs decreased oxidation stress to the nuclear DNA, which was shown by the decreased oh(8)dG production. It is suggested that to prevent various cancers, in addition to the known antiestrogenie, antityrosin kinase, and other effects. IFs appeared to promote excretion of oh(8)dG.