uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Alternative names
Publications (10 of 64) Show all publications
Beijer, K., Jönsson, M., Shaik, S., Behrens, D., Brunström, B. & Brandt, I. (2018). Azoles additively inhibit cytochrome P450 1 (EROD) and 19 (aromatase) in rainbow trout (Oncorhynchus mykiss). Aquatic Toxicology, 198, 73-81
Open this publication in new window or tab >>Azoles additively inhibit cytochrome P450 1 (EROD) and 19 (aromatase) in rainbow trout (Oncorhynchus mykiss)
Show others...
2018 (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 198, p. 73-81Article in journal (Refereed) Published
Abstract [en]

Antifungal azoles are widely used in medicine, agriculture, and material protection and several antifungal azoles have been found in environmental samples. Although these compounds were designed to inhibit fungal enzymes such as lanosterol-14-demethylase (cytochrome P450 (CYP) 51), it is well established that the inhibitory actions of azoles are not specific for fungal CYP isozymes.

We refined a gill filament assay to determine the inhibition of CYP1, measured as reduced 7-ethoxyresorufin-O-deethylase (EROD) activity, in rainbow trout (Oncorhynchus mykiss) gill tissue ex vivo. The advantage of this method is that both induction and inhibition of EROD are performed ex vivo. Among thirteen azoles studied, the five that caused the strongest inhibition of gill EROD activity at a concentration of 5 μM were selected for concentration–response assessment. These compounds (bifonazole, clotrimazole, imazalil, miconazole, and prochloraz) showed IC50 values ranging from 0.1 to 1.5 μM. CYP19 (aromatase) inhibition was measured using microsomes from rainbow trout brains. Concentration-response curves for CYP19 inhibition were determined for letrozole, bifonazole, clotrimazole, imazalil, miconazole and prochloraz, which gave IC50 values ranging from 0.02 to 3.3 μM. It was further found that mixtures of the five most potent azoles reduced both CYP1 and 19 catalytic activity in an additive fashion (IC50 = 0.7 μM and 0.6 μM, in the respective assay). Bifonazole (IC50 = 0.1 μM) is not previously known to inhibit CYP1 activity.

The additive inhibition of CYP1 and CYP19 catalytic activity is an important finding of the present study. We conclude that this additive action of azoles could mediate adverse impacts on CYP regulated physiological functions in environmentally exposed fish.

Keywords
Azole fungicide, EROD activity, cytochrome P450 (CYP), CYP1A, CYP19, aromatase, pharmaceutical, contaminant, chemical, fish, rainbow trout, gill, EROD aktivitet, cytokrom P450 (CYP), CYP1A, CYP19, aromatase, läkemedel, azol, fungicid, kemikalier, förorening, fisk, regnbågslax, gäle
National Category
Other Biological Topics
Research subject
Biology with specialization in Environmental Toxicology
Identifiers
urn:nbn:se:uu:diva-249010 (URN)10.1016/j.aquatox.2018.02.016 (DOI)000430630100008 ()
Funder
Mistra - The Swedish Foundation for Strategic Environmental Research
Available from: 2015-04-15 Created: 2015-04-10 Last updated: 2018-08-07Bibliographically approved
Pierozan, P., Andersson, M., Brandt, I. & Karlsson, O. (2018). The environmental neurotoxin beta-N-methylamino-L-alanine inhibits melatonin synthesis in primary pinealocytes and a rat model. Journal of Pineal Research, 65(1), Article ID e12488.
Open this publication in new window or tab >>The environmental neurotoxin beta-N-methylamino-L-alanine inhibits melatonin synthesis in primary pinealocytes and a rat model
2018 (English)In: Journal of Pineal Research, ISSN 0742-3098, E-ISSN 1600-079X, Vol. 65, no 1, article id e12488Article in journal (Refereed) Published
Abstract [en]

The environmental neurotoxin beta-N-methylamino-L-alanine (BMAA) is a glutamate receptor agonist that can induce oxidative stress and has been implicated as a possible risk factor for neurodegenerative disease. Detection of BMAA in mussels, crustaceans, and fish illustrates that the sources of human exposure to this toxin are more abundant than previously anticipated. The aim of this study was to determine uptake of BMAA in the pineal gland and subsequent effects on melatonin production in primary pinealocyte cultures and a rat model. Autoradiographic imaging of 10-day-old male rats revealed a high and selective uptake in the pineal gland at 30minutes to 24hours after C-14-L-BMAA administration (0.68mg/kg). Primary pinealocyte cultures exposed to 0.05-3mmol/L BMAA showed a 57%-93% decrease in melatonin synthesis in vitro. Both the metabotropic glutamate receptor 3 (mGluR3) antagonist Ly341495 and the protein kinase C (PKC) activator phorbol-12-myristate-13-acetate prevented the decrease in melatonin secretion, suggesting that BMAA inhibits melatonin synthesis by mGluR3 activation and PKC inhibition. Serum analysis revealed a 45% decrease in melatonin concentration in neonatal rats assessed 2weeks after BMAA administration (460mg/kg) and confirmed an inhibition of melatonin synthesis in vivo. Given that melatonin is a most important neuroprotective molecule in the brain, the etiology of BMAA-induced neurodegeneration may include mechanisms beyond direct excitotoxicity and oxidative stress.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
amyotrophic lateral sclerosis, parkinsonism-dementia complex, BMAA, developmental exposure, DOHaD, mGluR3, neurodegenerative disease, pineal gland, protein kinase C
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-360183 (URN)10.1111/jpi.12488 (DOI)000437132700009 ()29528516 (PubMedID)
Funder
Swedish Research Council FormasCarl Tryggers foundation
Available from: 2018-09-13 Created: 2018-09-13 Last updated: 2018-09-13Bibliographically approved
Andersson, M., Karlsson, O. & Brandt, I. (2018). The environmental neurotoxin β-N-methylamino-l-alanine (l-BMAA) is deposited into birds' eggs. Ecotoxicology and Environmental Safety, 147, 720-724
Open this publication in new window or tab >>The environmental neurotoxin β-N-methylamino-l-alanine (l-BMAA) is deposited into birds' eggs
2018 (English)In: Ecotoxicology and Environmental Safety, ISSN 0147-6513, E-ISSN 1090-2414, Vol. 147, p. 720-724Article in journal (Refereed) Published
Abstract [en]

C-carboxyl-labeled BMAA were compared. The results revealed a pronounced incorporation of radioactivity in the eggs, predominantly in the yolk but also in the albumen. Imaging analysis showed that the concentrations of radioactivity in the liver decreased about seven times between the 24h and the 72h time points, while the concentrations in egg yolk remained largely unchanged. At 72h the egg yolk contained about five times the concentration of radioactivity in the liver. Both BMAA preparations gave rise to similar distribution pattern in the bird tissues and in the eggs, indicating metabolic stability of the labeled groups. The demonstrated deposition into eggs warrants studies of BMAAs effects on bird development. Moreover, birds' eggs may be a source of human BMAA exposure, provided that the laying birds are exposed to BMAA via their diet.

Keywords
Birds' eggs, Cyanobacterial neurotoxin, Developmental toxicity, Human exposure, Secretion
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-342429 (URN)10.1016/j.ecoenv.2017.09.032 (DOI)000416199700090 ()28942274 (PubMedID)
Funder
Swedish Research Council Formas
Available from: 2018-02-20 Created: 2018-02-20 Last updated: 2018-03-02Bibliographically approved
Andersson, M., Ersson, L., Brandt, I. & Bergström, U. (2017). Potential transfer of neurotoxic amino acid beta-N-methylamino-L-alanine (BMAA) from mother to infant during breast-feeding: Predictions from human cell lines. Toxicology and Applied Pharmacology, 320, 40-50
Open this publication in new window or tab >>Potential transfer of neurotoxic amino acid beta-N-methylamino-L-alanine (BMAA) from mother to infant during breast-feeding: Predictions from human cell lines
2017 (English)In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 320, p. 40-50Article in journal (Refereed) Published
Abstract [en]

β-N-methylamino-alanine (BMAA) is a non-protein amino acid produced by cyanobacteria, diatoms and dinoflagellates. BMAA has potential to biomagnify in a terrestrial food chain, and to bioaccumulate in fish and shellfish. We have reported that administration of [14C]l-BMAA to lactating mice and rats results in a mother to off-spring transfer via the milk. A preferential enantiomer-specific uptake of [14C]l-BMAA has also been demonstrated in differentiated murine mammary epithelium HC11 cells. These findings, together with neurotoxic effects of BMAA demonstrated both in vitro and in vivo, highlight the need to determine whether such transfer could also occur in humans. Here, we used four cell lines of human origin to examine and compare the transport of the two BMAA enantiomers in vitro. The uptake patterns of [14C]l- and [14C]d-BMAA in the human mammary MCF7 cell line were in agreement with the results in murine HC11 cells, suggesting a potential secretion of BMAA into human breast milk. The permeability coefficients for both [14C]l- and [14C]d-BMAA over monolayers of human intestinal Caco2 cells supported an efficient absorption from the human intestine. As a final step, transport experiments confirmed that [14C]l-and [14C]d-BMAA can be taken up by human SHSY5Y neuroblastoma cells and even more efficiently by human U343 glioblastoma cells. In competition experiments with various amino acids, the ASCT2 specific inhibitor benzylserine was the most effective inhibitor of [14C]l-BMAA uptake tested here. Altogether, our results suggest that BMAA can be transferred from an exposed mother, via the milk, to the brain of the nursed infant.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
BMAA, Cellular transport, Amino acid transporters, Breast milk, Neurodegeneration
National Category
Cell Biology Developmental Biology
Research subject
Biology with specialization in Environmental Toxicology
Identifiers
urn:nbn:se:uu:diva-265857 (URN)10.1016/j.taap.2017.02.004 (DOI)000396798200006 ()28174119 (PubMedID)
Funder
Swedish Research Council Formas
Available from: 2015-11-03 Created: 2015-11-03 Last updated: 2017-05-02Bibliographically approved
Beijer, K., Björlenius, B., Shaik, S., Lindberg, R. H., Brunström, B. & Brandt, I. (2017). Removal of pharmaceuticals and unspecified contaminants in sewage treatment effluents by activated carbon filtration and ozonation: Evaluation using biomarker responses and chemical analysis. Chemosphere, 176, 342-351
Open this publication in new window or tab >>Removal of pharmaceuticals and unspecified contaminants in sewage treatment effluents by activated carbon filtration and ozonation: Evaluation using biomarker responses and chemical analysis
Show others...
2017 (English)In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 176, p. 342-351Article in journal (Refereed) Published
Abstract [en]

Traces of active pharmaceutical ingredients (APIs) and other chemicals are demonstrated in effluents from sewage treatment plants (STPs) and they may affect quality of surface water and eventually drinking water. Treatment of effluents with granular activated carbon (GAC) or ozone to improve removal of APIs and other contaminants was evaluated at two Swedish STPs, Kappala and Uppsala (88 and 103 APIs analyzed). Biomarker responses in rainbow trout exposed to regular and additionally treated effluents were determined. GAC and ozone treatment removed 87-95% of the total concentrations of APIs detected. In Kappala, GAC removed 20 and ozonation (7 g O-3/m(3)) 21 of 24 APIs detected in regular effluent. In Uppsala, GAC removed 25 and ozonation (5.4 g O-3/m(3)) 15 of 25 APIs detected in effluent. GAC and ozonation also reduced biomarker responses caused by unidentified pollutants in STP effluent water. Elevated ethoxyresorufin-O-deethylase (EROD) activity in gills was observed in fish exposed to effluent in both STPs. Gene expression analysis carried out in Kappala showed increased concentrations of cytochrome P450 (CYP1A5 and CYP1C3) transcripts in gills and of CYP1As in liver of fish exposed to effluent. In fish exposed to GAC- or ozone-treated effluent water, gill EROD activity and expression of CYP1As and CYP1C3 in gills and liver were generally equal to or below levels in fish held in tap water. The joint application of chemical analysis and sensitive biomarkers proved useful for evaluating contaminant removal in STPs with new technologies.

Keywords
Wastewater, Activated carbon, Ozonation, Pharmaceuticals, Biomarkers, Rainbow trout
National Category
Environmental Sciences Environmental Biotechnology
Identifiers
urn:nbn:se:uu:diva-322509 (URN)10.1016/j.chemosphere.2017.02.127 (DOI)000399849300039 ()28273541 (PubMedID)
Funder
Mistra - The Swedish Foundation for Strategic Environmental Research
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2017-05-30 Created: 2017-05-30 Last updated: 2017-05-30Bibliographically approved
Kalayou, S., Granum, C., Berntsen, H. F., Groseth, P. K., Verhaegen, S., Connolly, L., . . . Ropstad, E. (2016). Label-free based quantitative proteomics analysis of primary neonatal porcine Leydig cells exposed to the persistent contaminant 3-methylsulfonyl-DDE. Journal of Proteomics, 137, 68-82
Open this publication in new window or tab >>Label-free based quantitative proteomics analysis of primary neonatal porcine Leydig cells exposed to the persistent contaminant 3-methylsulfonyl-DDE
Show others...
2016 (English)In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 137, p. 68-82Article in journal (Refereed) Published
Abstract [en]

Evidence that persistent environmental pollutants may target the male reproductive system is increasing. The male reproductive system is regulated by secretion of testosterone by testicular Leydig cells, and perturbation of Leydig cell function may have ultimate consequences. 3-Methylsulfonyl-DDE (3-MeSO2-DDE) is a potent adrenal toxicants formed from the persistent insecticide DDT. Although studies have revealed the endocrine disruptive effect of 3-MeSO2-DDE, the underlying mechanisms at cellular level in steroidogenic Leydig cells remains to be established. The current study addresses the effect of 3-MeSO2-DDE on viability, hormone production and proteome response of primary neonatal porcine Leydig cells. The AlamarBlue (TM) assay was used to evaluate cell viability. Solid phase radioimmunoassay was used to measure concentration of hormones produced by both unstimulated and Luteinizing hormone (LH)-stimulated Leydig cells following 48 h exposure. Protein samples from Leydig cells exposed to a non-cytotoxic concentration of 3-MeSO2-DDE (10 mu M) were subjected to nano-LC-MS/MS and analyzed on a Q Exactive mass spectrometer and quantified using label-free quantitative algorithm. Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA) were carried out for functional annotation and identification of protein interaction networks. 3-MeSO2-DDE regulated Leydig cell steroidogenesis differentially depending on cell culture condition. Whereas its effect on testosterone secretion at basal condition was stimulatory, the effect on LH-stimulated cells was inhibitory. From triplicate experiments, a total of 6804 proteins were identified in which the abundance of 86 proteins in unstimulated Leydig cells and 145 proteins in LH-stimulated Leydig cells was found to be significantly regulated in response to 3-MeSO2-DDE exposure. These proteins not only are the first reported in relation to 3-MeSO2-DDE exposure, but also display small number of proteins shared between culture conditions, suggesting the action of 3-MeSO2-DDE on several targeted pathways, including mitochondrial dysfunction, oxidative phosphorylation, EIF2-signaling, and glutathione-mediated detoxification. Further identification and characterization of these proteins and pathways may build our understanding to the molecular basis of 3-MeSO2-DDE induced endocrine disruption in Leydig cells.

Keywords
Persistent organic pollutants, 3-Methylsulfonyl-DDE, Leydig cells, Steroidogenesis, Endocrine disruption, Proteomics, IPA, Sus scrofa
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-297547 (URN)10.1016/j.jprot.2015.12.007 (DOI)000374368800008 ()26691841 (PubMedID)
Funder
Swedish Research Council Formas, 2007-1267-10370-9
Available from: 2016-06-27 Created: 2016-06-23 Last updated: 2017-11-28Bibliographically approved
Zoeller, R. T., Bergman, A., Becher, G., Bjerregaard, P., Bomman, R., Brandt, I., . . . Vandenberg, L. (2016). The Path Forward on Endocrine Disruptors Requires Focus on the Basics [Letter to the editor]. Toxicological Sciences, 149(2), 272-272
Open this publication in new window or tab >>The Path Forward on Endocrine Disruptors Requires Focus on the Basics
Show others...
2016 (English)In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 149, no 2, p. 272-272Article in journal, Letter (Refereed) Published
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-296905 (URN)10.1093/toxsci/kfv329 (DOI)000371613900002 ()26811417 (PubMedID)
Available from: 2016-06-27 Created: 2016-06-20 Last updated: 2018-01-10Bibliographically approved
Gao, K., Yan, P., Tan, C.-l., Luo, Y.-h., Sun, J., Jonsson, M. E., . . . Tang, Y.-p. (2015). Application of Rainbow Trout CYP1 Gene Expression Patterns in Gill and Liver for Haihe River Bio-monitoring. Huanjing Kexue, 36(10), 3878-3883
Open this publication in new window or tab >>Application of Rainbow Trout CYP1 Gene Expression Patterns in Gill and Liver for Haihe River Bio-monitoring
Show others...
2015 (English)In: Huanjing Kexue, ISSN 0250-3301, Vol. 36, no 10, p. 3878-3883Article in journal (Refereed) Published
Abstract [en]

CYP1 subfamily genes in gills and liver of rainbow trout as biomarkers were studied to establish methods for quantitative mRNA expression analysis of these genes and to determine their expression pattern. Fish caged in various waters in the Haihe River (Tianjin) were analyzed. The mRNA expression patterns observed in Machangjian River and estuary site of Haihe River were markedly similar but at different levels, reflecting that those sites shared the similar pollution components but with different local pollution load. CYP1C1 and 1C3 were only induced at Gegu site and estuary site of Haihe River, indicating different types of CYP1 agonists in Machangjian River. Response patterns of multiple CYP1 genes in gills and liver could be applied in the monitoring strategy. The response patterns of CYP1 genes could be used for better understanding the relationship between complex mixtures of pollutants and biological response of organisms in aquatic environments.

National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-288997 (URN)
Available from: 2016-04-28 Created: 2016-04-28 Last updated: 2016-06-21Bibliographically approved
Andersson, M., Karlsson, O., Bergström, U., Brittebo, E. B. & Brandt, I. (2015). Correction: Maternal Transfer of the Cyanobacterial Neurotoxin β-N-Methylamino-L-Alanine (BMAA) via Milk to Suckling Offspring. PLoS ONE, 8(10), Article ID e78133.
Open this publication in new window or tab >>Correction: Maternal Transfer of the Cyanobacterial Neurotoxin β-N-Methylamino-L-Alanine (BMAA) via Milk to Suckling Offspring
Show others...
2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 10, article id e78133Article in journal (Refereed) Published
National Category
Cell Biology Developmental Biology
Identifiers
urn:nbn:se:uu:diva-265863 (URN)10.1371/journal.pone.0133110 (DOI)000358194900136 ()26172384 (PubMedID)
Available from: 2015-11-03 Created: 2015-11-03 Last updated: 2017-12-01Bibliographically approved
Bergman, Å., Becher, G., Blumberg, B., Bjerregaard, P., Bornman, R., Brandt, I., . . . Zoeller, R. T. (2015). Manufacturing doubt about endocrine disrupter science - A rebuttal of industry-sponsored critical comments on the UNEP/WHO report "State of the Science of Endocrine Disrupting Chemicals 2012". Regulatory toxicology and pharmacology, 73(3), 1007-1017
Open this publication in new window or tab >>Manufacturing doubt about endocrine disrupter science - A rebuttal of industry-sponsored critical comments on the UNEP/WHO report "State of the Science of Endocrine Disrupting Chemicals 2012"
Show others...
2015 (English)In: Regulatory toxicology and pharmacology, ISSN 0273-2300, E-ISSN 1096-0295, Vol. 73, no 3, p. 1007-1017Article in journal, Editorial material (Other academic) Published
Abstract [en]

We present a detailed response to the critique of "State of the Science of Endocrine Disrupting Chemicals 2012" (UNEP/WHO, 2013) by financial stakeholders, authored by Lamb et al. (2014). Lamb et al.'s claim that UNEP/WHO (2013) does not provide a balanced perspective on endocrine disruption is based on incomplete and misleading quoting of the report through omission of qualifying statements and inaccurate description of study objectives, results and conclusions. Lamb et al. define extremely narrow standards for synthesizing evidence which are then used to dismiss the UNEP/WHO 2013 report as flawed. We show that Lamb et al. misuse conceptual frameworks for assessing causality, especially the Bradford Hill criteria, by ignoring the fundamental problems that exist with inferring causality from empirical observations. We conclude that Lamb et al.'s attempt of deconstructing the UNEP/WHO (2013) report is not particularly erudite and that their critique is not intended to be convincing to the scientific community, but to confuse the scientific data. Consequently, it promotes misinterpretation of the UNEP/WHO (2013) report by non-specialists, bureaucrats, politicians and other decision makers not intimately familiar with the topic of endocrine disruption and therefore susceptible to false generalizations of bias and subjectivity.

Keywords
Endocrine disruption, EDCs, Endocrine disruptors
National Category
Pharmacology and Toxicology Public Health, Global Health, Social Medicine and Epidemiology Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-280181 (URN)10.1016/j.yrtph.2015.07.026 (DOI)000367279400042 ()26239693 (PubMedID)
Available from: 2016-03-08 Created: 2016-03-08 Last updated: 2018-01-10Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-5386-2400

Search in DiVA

Show all publications