In Vitro Analysis Of Inflammatory Responses Following Environmental Exposure To Pharmaceuticals And Inland Waters

摘要

Pharmaceuticals are regularly released into the environment; in particular non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Erythromycin, naproxen, furosemide and atenolol are reported to be stable for up to 1 year in the environment, which increases the risk for accumulation. In the present study we have measured the occurrence and concentration of Pharmaceuticals in river Viskan (Jossabron) downstream of a sewage treatment plant in Boras, Sweden. Pharmaceuticals and water samples were tested for potential human risk by evaluating inflammatory responses (NF-κB and AP-1) using human T24 bladder epithelial cells and Jurkat T-cells. NF-κB activity in T24 cells was significantly reduced by all NSAIDs analysed (diclofenac, ketoprofen, naproxen, ibuprophen and dextropropoxyphene), but also by trimethoprim, using environmentally relevant concentrations. NF-κB and AP-1 activation was further analysed in response to water samples collected from different locations in Sweden. Dose-dependent down-regulation of AP-1 activity in Jurkat cells was observed at all locations. At two locations (Joessabron and Almenaes) down-regulation of NF-κB was observed. In contrast, the NF-κB response was potentiated by exposure to water from both locations following activation of NF-κB by treatment with heat-killed Escherichia coli. To determine the involvement of Pharmaceuticals in the responses, T24 cells were exposed to the pharmaceutical mixture, based on the determined levels at Joessabron. This resulted in reduction of the NF-κB response following exposure to the pharmaceutical mixture alone while no potentiation was observed when cells were co-exposed to heat killed E. co!i and Pharmaceuticals. The obtained results demonstrate that the identified pharmaceuticals affect the inflammatory responses and furthermore indicate the presence of unknown substance(s) with the ability to potentiate inflammatory responses.