Human pharmaceuticals have been shown to be entering the aquatic environment in quantities sufficient to produce adverse effects to aquatic organisms, particularly fish. The impacts of synthetic oestrogens have been well documented, but other groups of steroidal pharmaceuticals have not yet been studied. Hence, the present research was designed to study synthetic glucocorticoids (GCs), which are used in large amounts as immunosuppressive and anti-inflammatory drugs. This study involved different approaches, including in silico, in vitro, in vivo and genomics, to assess the effects of GCs on fish. Using reliable data on consumption of GCs in the UK and the LF2000-WQX hydrological model, mean concentrations of GCs in the river Thames were predicted to be in the range from 30 ng/L to 850 ng/L. Mammalian cell lines were transiently transfected with trout corticosteroid receptors (GR1, GR2 and MR) and the transactivation abilities of ten of the most prescribed GCs in the UK were measured in vitro. All tested GCs showed significantly higher activity with GR2 than with GR1. In order to assess the impact of low concentrations of GCs in vivo, two chronic exposure experiments were conducted with adult fathead minnows (Pimephales promelas). Both experiments showed potency-related and concentration-related impacts on various endpoints. There was a concentration-related increase in plasma glucose concentrations and a decrease in blood lymphocyte count. Induction of secondary sexual characters in females suggests a concentration-related masculinisation of fathead minnows. There was a decreasing trend in plasma vitellogenin concentrations in female fish with increasing exposure concentration of GCs. Expression profiles of selected genes (PEPCK, GR and Vtg) in liver also demonstrated concentration-related effects at all three tested concentrations. Hence, it was not possible to define a no effect concentration for the tested GCs. This study probably provides reliable estimates of the likely range of concentrations of GCs in a typical river, impacted by effluent from many sewage treatment plants. The in vitro results indicate that all tested GCs bind to fish GR in a similar manner to that reported for mammalian receptors. The in vivo results suggest that GCs could cause effects at very low (as low as 100 ng/L) concentrations that could be environmentally-relevant. The immunosuppresive effects could make fish susceptible to disease and the reproductive effects may have population-level impacts. It is very likely that the effects of different GCs will be additive, as has been shown for oestrogenic chemicals. Therefore, this study warrants further environmental risk assessment of GCs, especially in mixture scenarios.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:543874 |
| Date | January 2011 |
| Creators | Kugathas, Subramaniam |
| Contributors | Sumpter, J. ; Routledge, E. |
| Publisher | Brunel University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://bura.brunel.ac.uk/handle/2438/6348 |
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