Suppression of lipid-hydroperoxide and DNA-adduct formation by isoflavone-containing soy hypocotyl tea in rats

Abstract

Objective: Phytoestrogen isoflavones (IFs) are considered to suppress estrogen-related cancers through their antiestrogenic activity. The antioxidant effect of IFs, however, has not been confirmed in an in vivo system, so suppression of hydroperoxide formation and resultant DNA adduct formation were studied.Metheds: The 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.Results: FeD 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.Conclusion: IFs and SHT showed antioxidant effects at physiological concentrations in an in 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 antiestrogenic, antityrosin kinase, and other effects. IFs appeared to promote excretion of oh 8 dG.

Iron Complexes of Flavonoids-Antioxidant Capacity and Beyond

“…A balance in ROS/RNS (e.g., hydroxyl, superoxide, nitric oxide, nitrogen dioxide, or peroxyl radicals together with non-radical hydrogen peroxide and peroxynitrite) is closely connected with the redox status of the cell that is influenced also by sulphur compounds (both sulphur-rich proteins and low-molecular thiols) and metal ions with chelating properties. Although most of results have been obtained from in vitro studies, increasing evidence indicates that flavonoids may display antioxidant functions also in vivo [ 33 , 34 ]. Due to the fact that they can be obtained from food in significant amounts, after ingestion of flavonoid-rich food, their blood levels can reach approximately micromolar concentrations, even if most of them are not absorbed or decomposed by gastrointestinal tract inhabiting microorganisms [ 35 ].…”