ENVIRONMENTAL ESTROGEN-MIMICS DISPLAY LIPOSOMAL MEMBRANE-ANTIOXIDANT ABILITY - IMPORTANCE OF MOLECULAR MODELING PREDICTIONS

Oestrogen-like biological activity towards male fish has been demonstr ated previously for degradation products of some detergents and indust rial feed-stock chemicals, released into water environments. The endog enous oestrogen, 17 beta-oestradiol, is a particularly effective membr ane-antioxidant, which may confer beneficial properties in addition to its genomic-mediated effects. Some of the most widely quoted environm ental oestrogen-mimics were tested for liposomal membrane-antioxidant ability, measured as inhibition of lipid peroxidation. 4-Nonylphenol a nd bisphenor A (4,4-isopropylidenediphenol) were best able to mimic th e antioxidant action of 17 beta-oestradiol by displaying effective inh ibition of liposomal-membrane lipid peroxidation, whereas dibutylphtha late ester and phthalic acid diethylether (PADE) were considerably les s effective antioxidants. The computer-based molecular modelling used in this study indicated a close structural similarity between these co mpounds and 17 beta-oestradiol (or the partial oestrogen/antioestrogen tamoxifen, a xenoestrogen drug used in breast cancer therapy), thus p redicting their environmental action as oestrogen-mimics: genomic effe cts mediated by oestrogen receptor binding and non-genomic effects as membrane-antioxidants. Furthermore, 17 beta-oestradiol itself liberate d initially into sewage-treatment lagoons from protein-bound 17 beta-o estradiol in human faeces, is now thought to be one of the main causes of the observed hermaphroditism of the male fish in the water-borne e nvironment. Dietary phytoestrogens and their metabolites (also membran e-antioxidants) may have a similar activity in partial feminization, w hich could result from their excretion throughout the environment (aqu atic and soil). Computer-assisted predictions have proved valuable in these comparative studies on these environmental xenoestrogens in the liposomal model-membrane system and could be generally utilized to mon itor the likely extent of oestrogenic exposure after discharge of part icular chemicals in industrial, domestic and sewage-treatment effluent s. Paradoxically, a reduction in reproductive capacity in these fish m ay be, in part, compensated for by protection of their membranes again st the oxidative stress generated by exposure to other pollutants in w ater environments. (C) 1998 Society of Chemical Industry.