Effects of oestrogenic chemicals on the liver

Abstract

Our environment and diet contains a variety of man-made endocrine disrupting chemicals which may pose a significant health threat for wildlife and humans. In particular, there is increasing concern regarding the adverse effects caused by xenoestrogens which are believed to trigger many endocrine-related diseases. Since high systemic levels of oestrogens are cholestatic, it was investigated whether xenoestrogens are able to cause adverse hepatic effects in vivo in mouse models and whether these effects are mediated by interaction with the murine oestrogen receptors (ERs). The food dye tartrazine has previously been shown to activate the human ERα and intraperitoneal injection caused cholestasis in mice. In this study, tartrazine failed to activate murine ERα and two murine ERβ variants in vitro suggesting that cholestasis occurred independent of the ERs. Data indicate, however, that tartrazine, its major metabolites and a contaminant inhibited murine dopamine sulfotransferase. Considering the role of sulfotransferases in bile acid secretion, these findings suggest that impairment of bile acid sulfation and subsequent secretion may be a key event in tartrazine-mediated cholestasis. Oral exposure to tartrazine caused inflammation in the liver and gastrointestinal tract in vivo in mice without evidence of cholestatic effects. Several soil extracts prepared from soil samples collected from around an urban landfill site activated human and murine ERα and two murine ERβ variants in vitro. Pooled oestrogenic soil extracts had mild cholestatic effects in a mouse model. Given the cholestatic features of the liver disease primary biliary cholangitis (PBC), which is linked to exposure to xenobiotics associated with a toxic environment and proximities to waste sites, environmental xenoestrogens could be a component of a xenobiotic insult that triggers PBC. These findings indicate that if significant exposure to environmental xenoestrogens occurs, they can have adverse hepatic effects and may be part of a trigger process in cholestatic liver diseases.