Uptake and biological effects of environmentally relevant concentrations of the nonsteroidal anti-inflammatory pharmaceutical diclofenac in the rainbow trout (Oncorhynchus mykiss)

Diclofenac, a nonsteroidal anti-inflammatory drug, is widely detected in surface waters and can potentially cause deleterious effects in fish. Here, we investigated the biological effects of 21-day exposure to waterborne diclofenac at environmentally relevant concentrations (0, 0.5, 1, 5, and 25 µg/L) in rainbow trout. Accumulation of diclofenac in the bile was measured and responses in selected tissues were assessed via changes in the expression of selected genes (cytochrome P450 (cyp) 1a1, cyclooxygenase (cox) 1 and 2, and p53) involved in metabolism of xenobiotics, prostaglandin synthesis, and cell cycle control, respectively, together with histopathological alterations in these tissues. Diclofenac accumulated in the bile by a factor of between 509 ± 27 and 657 ± 25 and various metabolites were putatively identified as hydroxydiclofenac, diclofenac methyl ester, and the potentially reactive metabolite hydroxydiclofenac glucuronide. Expression levels of both cox1 and cox2 in liver, gills, and kidney were significantly reduced by diclofenac exposure from only 1 µg/L. Expression of cyp1a1 was induced in the liver and the gills but inhibited in the kidney of exposed fish. Diclofenac exposure induced tubular necrosis in the kidney and hyperplasia and fusion of the villi in the intestine from 1 µg/L. This study demonstrates that subchronic exposure to environmental concentrations of diclofenac can interfere with the biochemical functions of fish and lead to tissue damage, highlighting further the concern about this pharmaceutical in the aquatic environment

A new approach for plasma (xeno)metabolomics based on solid-phase extraction and nanoflow liquid chromatography-nanoelectrospray ionisation mass spectrometry

No description supplie

Distinguishing between the metabolome and xenobiotic exposome in environmental field samples analysed by direct-infusion mass spectrometry based metabolomics and lipidomics

No description supplie

Metabolomics reveals target and off-target toxicities of a model organophosphate pesticide to roach (rutilus rutilus): implications for biomonitoring

No description supplie

Bioassay-directed identification of novel antiandrogenic compounds in bile of fish exposed to wastewater effluents

No description supplie

Environmental health impacts of equine estrogens derived from hormone replacement therapy

Many factors have been considered in evaluations of the risk-benefit balance of hormone replacement therapy (HRT), used for treating menopausal symptoms in women, but not its potential risks for the environment. We investigated the possible environmental health implications of conjugated equine estrogens (CEEs), the most common components of HRT, including their discharge into the environment, their uptake, potency, and ability to induce biological effects in wildlife. Influents and effluents from four UK sewage treatment works (STWs), and bile of effluent-exposed fish, were screened for six equine estrogens. In vitro estrogen receptor (ER) activation assays were applied in humans and fish to compare their potencies, followed by in vivo exposures of fish to equine estrogens and evaluation of bioaccumulation, estrogenic responses, and ER gene expression. The equine estrogen equilenin (Eqn), and its metabolite 17ß-dihydroequilenin (17ß-Eqn), were detected by tandem GC-MSMS in all STW influent samples and 83% of STW effluent samples analyzed, respectively, at low concentrations (0.07-2.6 ng/L) and were taken-up into effluent-exposed fish. As occurs in humans, these estrogens bound to and activated the fish ERs, with potencies at ERa 2.4-3490% of that for 17ß-estradiol. Exposure of fish for 21 days to Eqn and 17ß-Eqn induced estrogenic responses including hepatic growth and vitellogenin production at concentrations as low as 0.6-4.2 ng/L. Associated with these effects were inductions of hepatic ERa and ERß1 gene expression, suggesting ER-mediated mechanism(s) of action. These data provide evidence for the discharge of equine estrogens from HRT into the aquatic environment and highlight a strong likelihood that these compounds contribute to feminization in exposed wildlife