| 1. |
- Gunnarsson, Lina-Maria, 1977, et al.
(author)
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Pharmaceutical industry effluent diluted 1:500 affects global gene expression, cytochrome P4501A activity and plasma phosphate in fish
- 2009
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In: Environmental Toxicology and Chemistry. - : Society of Environmental Toxicology and Chemistry (SETAC). - 0730-7268 .- 1552-8618. ; 28:12, s. 2639-2647
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Journal article (peer-reviewed)abstract
- Patancheru, near Hyderabad, India, is a major production site for the global bulk drug market. Approximately 90 manufacturers send their wastewater to a common treatment plant in Patancheru. Extraordinary high levels of a wide range of pharmaceuticals have recently been demonstrated in the treated effluent. As little as 0.2% of this effluent can strongly reduce the growth rate of tadpoles, but the underlying mechanisms of toxicity are not known. To begin addressing how the effluent affects aquatic vertebrates, rainbow trout (Oncorhynchus mykiss) were exposed to 0.2% effluent for five days. Several physiological endpoints, together with effects on global hepatic gene expression patterns, were analyzed. The exposed fish showed both an induction of hepatic cytochrome P450 1A (CYP1A) gene expression, as well as enzyme activity. Clinical blood chemistry analyses revealed an increase in plasma phosphate levels, which in humans indicates impaired kidney function. Several oxidative stress-related genes were induced in the livers; however, no significant changes in antioxidant enzyme activities or in the hepatic glutathione levels were found. Furthermore, estrogen-regulated genes were slightly up-regulated following exposure, and moderate levels of estriol were detected in the effluent. The present study identifies changes in gene expression triggered by exposure to a high dilution of the effluent, supporting the hypothesis that these fish are responding to chemical exposure. The pattern of regulated genes may contribute to the identification of mechanisms of sub-lethal toxicity, as well as illuminate possible causative agents.
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| 2. |
- Cuklev, Filip, 1981, et al.
(author)
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Does ketoprofen or diclofenac pose the lowest risk to fish?
- 2012
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In: Journal of Hazardous Materials. - : Elsevier BV. - 0304-3894 .- 1873-3336. ; 229-230, s. 100-106
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Journal article (peer-reviewed)abstract
- Ketoprofen and diclofenac are non-steroidal anti-inflammatory drugs (NSAIDs) often used for similar indications, and both are frequently found in surface waters. Diclofenac affects organ histology and gene expression in fish at around 1 mu g/L. Here, we exposed rainbow trout to ketoprofen (1, 10 and 100 mu g/L) to investigate if this alternative causes less risk for pharmacological responses in fish. The bioconcentration factor from water to fish blood plasma was <0.05(4 for diclofenac based on previous studies). Ketoprofen only reached up to 0.6 parts per thousand of the human therapeutic plasma concentration, thus the probability of target-related effects was estimated to be fairly low. Accordingly, a comprehensive analysis of hepatic gene expression revealed no consistent responses. In some contrast, trout exposed to undiluted, treated sewage effluents bioconcentrated ketoprofen and other NSAIDs much more efficiently, according to a meta-analysis of recent studies. Neither of the setups is however an ideal representation of the field situation. If a controlled exposure system with a single chemical in pure water is a reasonable representation of the environment, then the use of ketoprofen is likely to pose a lower risk for wild fish than diclofenac, but if bioconcentration factors from effluent-exposed fish are applied, the risks may be more similar.
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| 3. |
- Albertsson, Eva, 1979, et al.
(author)
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Induction of hepatic carbonyl reductase/20beta-hydroxysteroid dehydrogenase mRNA in rainbow trout downstream from sewage treatment works--possible roles of aryl hydrocarbon receptor agonists and oxidative stress.
- 2010
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In: Aquatic toxicology (Amsterdam, Netherlands). - : Elsevier BV. - 1879-1514 .- 0166-445X. ; 97:3, s. 243-9
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Journal article (peer-reviewed)abstract
- Carbonyl reductase/20beta-hydroxysteroid dehydrogenase (CR/20beta-HSD) serves both as a key enzyme in the gonadal synthesis of maturing-inducing hormone in salmonids, and as an enzyme protecting against certain reactive oxygen species. We have previously shown that mRNA of the hepatic CR/20beta-HSD B isoform is increased in rainbow trout caged downstream from a Swedish sewage treatment plant. Here, we report an increase of both the A as well as B form in fish kept downstream from a second sewage treatment plant. The two mRNAs were also induced in fish hepatoma cells in vitro after exposure to effluent extract. This indicates that the effects observed in vivo could be a direct effect on the liver, i.e. the mRNA induction does not require a signal from any other organ. When fish were exposed in vivo to several effluents treated with more advanced methods (ozone, moving bed biofilm reactor or membrane bioreactor) the expression of hepatic mRNA CR/20beta-HSD A and B was significantly reduced. Their abundance did not parallel the reduction of estrogen-responsive transcripts, in agreement with our previous observations that ethinylestradiol is not a potent inducer. Treatment with norethisterone, methyltestosterone or hydrocortisone in vivo did not induce the hepatic CR/20beta-HSD A and B mRNA expression. In contrast, both isoforms were markedly induced by the aryl hydrocarbon receptor agonist beta-naphthoflavone as well as by the pro-oxidant herbicide paraquat. We hypothesize that the induction of CR/20beta-HSD A and B by sewage effluents could be due to anthropogenic contaminants stimulating the aryl hydrocarbon receptor and/or causing oxidative stress.
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| 4. |
- Berglund, Åsa, 1978-, et al.
(author)
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Oxidative stress in pied flycatcher (Ficedula hypoleuca) nestlings from metal contaminated environments in northern Sweden.
- 2007
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In: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 105:3, s. 330-339
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Journal article (peer-reviewed)abstract
- Metals have been shown to induce oxidative stress in animals. One of the most metal polluted terrestrial environments in Sweden is the surroundings of a sulfide ore smelter plant located in the northern part of the country. Pied flycatcher nestlings (Ficedula hypoleuca) that grew up close to the industry had accumulated amounts of arsenic, cadmium, mercury, lead, iron and zinc in their liver tissue. The aim of this study was to investigate if pied flycatcher nestlings in the pollution gradient of the industry were affected by oxidative stress using antioxidant molecules and enzyme activities. The antioxidant assays were also evaluated in search for useful biomarkers in pied flycatchers. This study indicated that nestlings in metal contaminated areas showed signs of oxidative stress evidenced by up regulated hepatic antioxidant defense given as increased glutathione reductase (GR) and catalase (CAT) activities and slightly but not significantly elevated lipid peroxidation and glutathione-S-transferase (GST) activities. Stepwise linear regression indicated that lipid peroxidation and CAT activities were influenced mostly by iron, but iron and lead influenced the CAT activity to a higher degree. Positive relationships were found between GST and lead as well as GR activities and cadmium. We conclude that GR, CAT, GST activities and lipid peroxidation levels may function as useful biomarkers for oxidative stress in free-living pied flycatcher nestlings exposed to metal contaminated environments.
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| 5. |
- Cuklev, Filip, 1981, et al.
(author)
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Diclofenac in fish : blood plasma levels similar to human therapeutic levels affect global hepatic gene expression
- 2011
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In: Environmental Toxicology and Chemistry. - New York : Pergamon. - 0730-7268 .- 1552-8618. ; 30:9, s. 2126-2134
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Journal article (peer-reviewed)abstract
- Diclofenac is a non-steroidal anti-inflammatory drug frequently found in the aquatic environment. Previous studies have reported histological changes in the liver, kidney and gills of fish at concentrations similar to those measured in treated sewage effluents (approximately 1 µg/L). Analyses or predictions of blood plasma levels in fish allow a direct comparison with human therapeutic plasma levels, and may therefore be used to indicate a risk for pharmacological effects in fish. To relate internal exposure to a pharmacological interaction we investigated global hepatic gene expression together with bioconcentration in blood plasma and liver of rainbow trout (Oncorhynchus mykiss) exposed to waterborne diclofenac. At the highest exposure concentration (81.5 µg/L) the fish plasma concentration reached approximately 88% of the human therapeutic levels (C(max) ) after two weeks. Using an oligonucleotide microarray followed by quantitative PCR we found extensive effects on hepatic gene expression at this concentration, and some genes were found to be regulated down to the lowest concentration tested (1.6 µg/L) corresponding to approximately 1.5% of the human C(max) . Thus, at concentrations detected in European surface waters, diclofenac can affect the expression of multiple genes in exposed fish. Functional analysis of differentially expressed genes revealed effects on biological processes such as inflammation and immune response, in agreement with the mode of action of diclofenac in mammals. In contrast to some previously reported results, the bioconcentration factor was found to be stable (4.02 ± 0.75 for blood plasma and 2.54 ± 0.36 for liver) regardless of the water concentration. Environ. Toxicol. Chem. © 2011 SETAC.
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| 6. |
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| 7. |
- Gunnarsson, Lina-Maria, 1977, et al.
(author)
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Comparison of six different sewage treatment processes-Reduction of estrogenic substances and effects on gene expression in exposed male fish
- 2009
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In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 407:19, s. 5235-5242
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Journal article (peer-reviewed)abstract
- Treated sewage effluents often contain a mixture of estrogenic compounds in low concentrations. The total combined activity of these, however, may be sufficiently high to affect the reproduction of aquatic vertebrates. The introduction of advanced treatment technologies has been suggested as a way to remove micro-contaminants, including estrogenic substances. In this study, one municipal influent was treated with six different processes in parallel on a semi-large scale in order to assess their potential to reduce substances that could contribute to estrogenic effects in male fish. The effluent from a conventional, activated sludge treatment line was compared to a similarly treated effluent with a final sand-filtering step. The addition of ozonation (15 g O-3/m(3)). a moving bed biofilm reactor (MBBR) or both in combination was also evaluated. There was also a separate treatment line that was based on a membrane bioreactor. A small battery of hepatic estrogen-responsive genes was measured in the exposed fish using quantitative PCR. Concentrations of steroid estrogens and estrogenic phenols in the effluents were measured by GC-ECNI-MS. The ozonated effluents were the only tested effluents for which all measured biological effects in exposed fish were removed. Chemical data suggested that the MBBR technology was equally effective in removing the analyzed estrogens; however, elevated expression of estrogen-responsive genes suggested that some estrogenic substances were still present in the effluent. The membrane bioreactor removed most of the measured estrogens and it reduced the induction of the estrogen-responsive genes. However, fish exposed to this effluent had significantly enlarged livers. Given that the same influent was treated in parallel with a broad set of technologies and that the chemical analyses were combined with an in vivo assessment of estrogenic responses, this study provides valuable input into the assessment of advanced treatment processes for removing estrogenic substances.
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| 8. |
- Hanson, Niklas, 1976, et al.
(author)
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Spatial and annual variation to define the normal range of biological endpoints: an example with biomarkers in perch
- 2010
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In: Environmental Toxicology and Chemistry. - 0730-7268. ; 29:11, s. 2616-2624
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Journal article (peer-reviewed)abstract
- A signal from a biological endpoint can be considered evidence of environmental impact only if it is known that similar signals are unlikely to occur naturally. Using multiple reference sites, the normal range can be estimated. This can be defined as the span that includes 95% of the reference sites. If an investigated site is outside this range, it is interpreted as evidence of impact. The choice of reference sites is thus important for the outcome of the study. Here, biomarker levels in perch (Perca fluviatilis) at a potentially impacted site were compared to different types of reference data. The potentially impacted site was located close to a densely populated area. Four reference sites were located in relatively undisturbed areas on the Swedish Baltic coast. Furthermore, historical data from one of the reference sites were included. The present study showed that multiple reference sites are needed to avoid the risk of interpreting natural variation as impact. The number of reference sites needed depends on the desired level of statistical power. An alternative to multiple reference sites may be to use historical data to estimate the natural variation. However, historical data can include temporal variation due to factors that may not be relevant for the hypothesis that is tested, e.g., climatic variation or changed background levels of pollution.
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| 9. |
- Kristiansson, Erik, 1978, et al.
(author)
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Characterization of the Zoarces viviparus liver transcriptome using massively parallel pyrosequencing
- 2009
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In: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 10:345
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Journal article (peer-reviewed)abstract
- Background The teleost Zoarces viviparus (eelpout) lives along the coasts of Northern Europe and has long been an established model organism for marine ecology and environmental monitoring. The scarce information about this species genome has however restrained the use of efficient molecular-level assays, such as gene expression microarrays. Results In the present study we present the first comprehensive characterization of the Zoarces viviparus liver transcriptome. From 400,000 reads generated by massively parallel pyrosequencing, more than 50,000 pieces of putative transcripts were assembled, annotated and functionally classified. The data was estimated to cover roughly 40% of the total transcriptome and homologues for about half of the genes of Gasterosteus aculeatus (stickleback) were identified. The sequence data was consequently used to design an oligonucleotide microarray for large-scale gene expression analysis. Conclusion Our results show that one run using a Genome Sequencer FLX from 454 Life Science/Roche generates enough genomic information for adequate de novo assembly of a large number of genes in a higher vertebrate. The generated sequence data, including the validated microarray probes, are publicly available to promote genome-wide research in Zoarces viviparus.
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| 10. |
- Larsson, Åke, 1944, et al.
(author)
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Kustfisk - hälsa
- 2010
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In: HAVET 2010. - 1654-6741.
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Journal article (other academic/artistic)
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