Biomedical subjects

Manfred Metzler

Publications and source records attributed to Manfred Metzler.

21 records · Page 2Linked to original sources

PubMed2002

Oxidative metabolism and genotoxic potential of major isoflavone phytoestrogens.

The soy isoflavones daidzein, genistein and glycitein are extensively metabolized by rat liver microsomes to a variety of catechol metabolites. Hydroxylated metabolites of daidzein and genistein have also been demonstrated in incubations with human hepatic microsomes and in the urine of humans after ingestion of soy food. Although the microsomal metabolism of formononetin and biochanin A is dominated by demethylation to daidzein and genistein, respectively, catechols of the parent isoflavones and of the demethylation products are also formed. Thus, oxidative metabolism appears to be common among isoflavones and may have implications for their biological activities. As genistein but not daidzein exhibits clastogenic activity in cultured mammalian cells, the role of oxidative metabolism for the genotoxicity of isoflavones is of particular interest.

Estrogens, Non-Steroidal↗

PubMed2002

Oxidative metabolites and genotoxic potential of mammalian and plant lignans in vitro.

Certain plant lignans, e.g. secoisolariciresinol and matairesinol, are converted by the intestinal microflora to the mammalian lignans enterodiol and enterolactone, which are associated with beneficial health effects in humans. The metabolism of both mammalian and plant lignans in animals and humans is poorly understood, and most studies so far have focused on the conjugation of these diphenolic compounds. However, recent studies have demonstrated that mammalian and plant lignans are good substrates for cytochrome p450-mediated reactions, leading to numerous products of aliphatic and aromatic hydroxylation with microsomes in vitro. The current knowledge of the oxidative metabolism of food-related lignans is briefly reviewed in this paper, including published as well as unpublished data from our laboratory. Moreover, data on the genotoxic potential of the mammalian and plant lignans, determined at various endpoints in cultured mammalian cells, are included in this review.

Animals↗

PubMed2002

Metabolism and lack of DNA reactivity of the mycotoxin ochratoxin a in cultured rat and human primary hepatocytes.

It is still unclear whether the carcinogenic mycotoxin ochratoxin A (OTA) is bioactivated to DNA-binding metabolites in rodents and humans. Therefore, we have incubated cultured rat and human primary hepatocytes with noncytotoxic concentrations of (3)H-OTA ranging from 10(-7) to 10(-5) M for 8 h and determined its metabolism and covalent DNA binding. In rat hepatocytes, OTA was metabolized to small amounts of three products, which were further studied by electrospray ionization (ESI)-MS/MS techniques. In addition to 4-hydroxy-OTA, which is a known product of OTA biotransformation, two novel metabolites were detected and tentatively identified as hexose and pentose conjugates of OTA. The in vitro induction with 3-methylcholanthrene (3MC) increased the formation of 4-hydroxy-OTA but did not alter the formation of the conjugated metabolites. No covalent binding of (3)H-OTA or its metabolites to DNA was observed in rat hepatocytes with or without 3MC induction with a limit of detection of 2 adducts per 10(9) nucleotides. However, the cellular ratio of reduced glutathione to oxidized glutathione was significantly decreased by treatment with OTA. In cultured human hepatocytes, (3)H-OTA was only very poorly metabolized, and no covalent DNA binding was observed. In conclusion, the results of this in vitro study do not support the notion that OTA has the potential to undergo metabolic activation and form covalent DNA adducts in rodents and humans.

Animals↗