In vitro analysis of inflammatory responses following environmental exposure to pharmaceuticals and inland waters.
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 (Jössabron) downstream of a sewage treatment plant in Borås, Sweden. Pharmaceuticals and water samples were tested for potential human risk by evaluating inflammatory responses (NF-kappaB and AP-1) using human T24 bladder epithelial cells and Jurkat T-cells. NF-kappaB 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-kappaB 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 (Jössabron and Almenäs) down-regulation of NF-kappaB was observed. In contrast, the NF-kappaB response was potentiated by exposure to water from both locations following activation of NF-kappaB 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 Jössabron. This resulted in reduction of the NF-kappaB response following exposure to the pharmaceutical mixture alone while no potentiation was observed when cells were co-exposed to heat killed E. coli 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.
Khalaf
Hazem
H
Biology, Orebro Life Science Center, School of Science and Technology, Orebro University, SE-701 82 Orebro, Sweden.
Salste
Lotta
L
Karlsson
Patrik
P
Ivarsson
Per
P
Jass
Jana
J
Olsson
Per-Erik
PE
D045744:Cell Line, Tumor; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D019169:Jurkat Cells; D016328:NF-kappa B / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000032:analysis*; D045483:Rivers; D052616:Solid Phase Extraction; D013548:Sweden; D018808:Transcription Factor AP-1 / Q000032:analysis*; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000494:pharmacology*; D015262:Xenobiotics / Q000032:analysis / Q000494:pharmacology*
D016328:NF-kappa B; D004364:Pharmaceutical Preparations; D018808:Transcription Factor AP-1; D014874:Water Pollutants, Chemical; D015262:Xenobiotics