Oxysterols profiles in zebrafish (Danio rerio) embryos exposed to bisphenol A.

INTRODUCTION: Oxysterols are cholesterol oxidation products and bioactive lipids involved in developmental signalling pathways, embryonic and postembryonic tissue patterning and homeostasis. The embryonic period is a very sensitive window of exposure to bisphenol A (BPA), hence the role of BPA on the levels of oxysterols in the very early stages of zebrafish embryogenesis is a relevant novel field of investigation. OBJECTIVES: To compare the role of BPA on oxysterols levels in zebrafish embryos at 8 and 24 h post fertilization (hpf) with cytochromes P450 (CYPs)-modulating chemicals (carbamazepine, ketoconazole, and hydrogen peroxide). METHODS: Upon a dose range finding, zebrafish embryos were exposed to environmentally relevant (0.04 µM) and toxicological (17.5 µM) BPA concentrations. Seven oxysterols were profiled by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). RESULTS: Similarly to the CYPs-modulating chemicals, BPA caused: i) no significant changes at 8 hpf and ii) a dose-dependent increase of total oxysterols at 24 hpf, with 27-hydroxycholesterol as the most regulated oxysterol. DISCUSSION: In the first day post-fertilization of the zebrafish embryos, the role of BPA alike a CYPs-modulating chemical was confirmed by the similar oxysterol changes observed with the already known CYPs-modulating chemicals.

Oxysterols Profile in Zebrafish Embryos Exposed to Triclocarban and Propylparaben-A Preliminary Study.

Oxysterols have long been considered as simple by-products of cholesterol metabolism, but they are now fully designed as bioactive lipids that exert their multiple effects through their binding to several receptors, representing endogenous mediators potentially involved in several metabolic diseases. There is also a growing concern that metabolic disorders may be linked with exposure to endocrine-disrupting chemicals (EDCs). To date, there are no studies aimed to link EDCs exposure to oxysterols perturbation-neither in vivo nor in vitro studies. The present research aimed to evaluate the differences in oxysterols levels following exposure to two metabolism disrupting chemicals (propylparaben (PP) and triclocarban (TCC)) in the zebrafish model using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Following exposure to PP and TCC, there were no significant changes in total and individual oxysterols compared with the control group; however, some interesting differences were noticed: 24-OH was detected only in treated zebrafish embryos, as well as the concentrations of 27-OH, which followed a different distribution, with an increase in TCC treated embryos and a reduction in zebrafish embryos exposed to PP at 24 h post-fertilization (hpf). The results of the present study prompt the hypothesis that EDCs can modulate the oxysterol profile in the zebrafish model and that these variations could be potentially involved in the toxicity mechanism of these emerging contaminants.