The study of feasibility of green tea treatment on fetus: From chemistry to treatment.

摘要

Hypoxia and reperfusion can result in many pathological complications in the fetus including retinopathy, ischemic encephalopathy and even stillbirth. The adverse effects are due to excess production of free radicals that attack vital bio-molecules such as DNA and enzymes. Antioxidant treatment may be a way to alleviate oxidative stress. Green tea is a source of antioxidants. It contains polyphenols mainly catechins, that possess high reducing power and low toxicity. Major catechin compounds in green tea are (+)-catechin (C), (-)-epicatechin (EC, (-)-gallocatechin (GC), (-)-epigallocatechin (EGC), (-)-catechin gallate (CG), (-)-epicatechin gallate (ECG), (-)-gallocatechin gallate (GCG) and (-)-epigallocatechin gallate (EGCG). Accordingly, catechins may be ideal agents for antioxidant treatment of the fetus exposed to hypoxia during pregnancy.; In this study, pregnant rat dams were fed green tea extract in an attempt to raise catechin levels in the rat embryo in order to scavenge free radicals. To test this hypothetical application, we first established analytical methods to evaluate oxidative stress and catechins levels of the fetus in vivo. The methodologies included assaying F2-isoprostanes in cord blood and determining catechin levels in biological fluids and tissues. We further utilized these new sensitive analytical methods to investigate the pharmacokinetics of the catechins in maternal rat plasma, whole embryos and embryonic organs. Since no data has been previously reported on the toxic effects of catechins on embryos, we also tested the toxic effects of various concentrations of catechins on the developing embryonic features in embryo culture.; In the animal experiments, rat mothers, at the 15.5th gestation day, were intragastrically administrated a single dose of green tea extract. The pharmacokinetic profiles of catechins in maternal plasma, whole embryos and embryonic organs were investigated. The catechins GC, ECG, C, EC, were found to exhibit non-linear capacity limited pharmacokinetic behaviour implying their metabolism or absorption was saturated. Catechin gallates, EGCG and ECG, appeared to exhibit enterohepatic re-circulation behaviour. Peak time was about 1 hour for both groups of catechins; the half life of the catechin group was about 1 hour while that of EGCG and ECG was about 3.7 hours. EC, EGC and EGCG were the dominant compounds present in plasma. All catechins exhibited a consecutive one-compartment model in the embryo, where EGCG, ECG, EGC and EC were dominant compounds and ECG had the highest penetrability. (Abstract shortened by UMI.)