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Azoles inhibit cytochrome P450 enzymes in rainbow trout involved in biotransformation and steroid hormone synthesis additively
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
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2015 (English)Manuscript (preprint) (Other academic)
Place, publisher, year, edition, pages
2015.
Keyword [en]
Azole fungicide, EROD activity, cytochrome P450 (CYP), CYP1A, CYP19, aromatase, pharmaceutical, contaminant, chemical, fish, rainbow trout, gill
Keyword [sv]
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: urn:nbn:se:uu:diva-249010OAI: oai:DiVA.org:uu-249010DiVA: diva2:805578
Available from: 2015-04-15 Created: 2015-04-10 Last updated: 2017-06-30Bibliographically approved
In thesis
1. Azoles and Contaminants in Treated Effluents Interact with CYP1 and CYP19 in Fish:
Open this publication in new window or tab >>Azoles and Contaminants in Treated Effluents Interact with CYP1 and CYP19 in Fish:
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Numerous contaminants are present in mixtures in the aquatic environment. Among these are the azoles, a group of chemicals that includes both pharmaceuticals and pesticides. Azole fungicides are designed to inhibit lanosterol 14-demethylase (cytochrome P450 (CYP) 51), while other azoles are intended to inhibit aromatase (CYP19), i.e. the enzyme catalyzing biosynthesis of estrogens. In fish, a variety of CYP enzymes are involved in biotransformation of waterborne contaminants, and in metabolism of endogenous compounds including steroidal hormones. The induction of CYP1A protein and 7-ethoxyresorufin O-deethylase (EROD) activity are common biomarkers for exposure to aryl hydrocarbon receptor (AhR) agonists in fish. We developed an assay to measure inhibition of CYP1A activity (EROD) in three-spined stickleback and rainbow trout gill tissue ex vivo. Several azole fungicides were found to be potent inhibitors of CYP1A activity. A wastewater effluent containing high concentrations of pharmaceuticals was also shown to inhibit CYP1A activity. Further, several azoles inhibited CYP19 activity in rainbow trout brain microsomes in vitro. Azole mixtures reduced both CYP1A and CYP19 activity monotonically and in an additive way. Given the additive action of the azoles, studies to determine adverse effects of azole mixtures on CYP-regulated physiological functions in fish are needed. Induction of EROD and of gene expression of CYP1 in several organs was observed in an in vivo exposure with the same effluent shown to inhibit EROD. This finding could imply that there was a mixture of AhR agonists and CYP1A inhibitors in the effluent. Finally, wastewater treatment technologies were evaluated using biomarker responses in rainbow trout exposed to effluents of different treatments. The results from chemical analysis together with the biomarker results show that ozone and granulated active carbon treatment removed most pharmaceuticals, as well as AhR agonists and other chemicals present in the regular effluent. This part of the thesis demonstrates that biomarkers in fish such as induction of CYP1 gene expression are applicable to evaluate the efficiency of different treatment technologies for wastewater.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 42 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1255
Keyword
Azole, fungicide, chemical, CYP1A, CYP19, EROD, aromatase, effluent, STP, wastewater, fish, stickleback, rainbow trout
National Category
Natural Sciences Biological Sciences
Research subject
Biology with specialization in Environmental Toxicology
Identifiers
urn:nbn:se:uu:diva-251295 (URN)978-91-554-9248-9 (ISBN)
Public defence
2015-06-04, Zootissalen, EBC, Villavägen 9, Uppsala, 13:00 (English)
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Supervisors
Available from: 2015-05-13 Created: 2015-04-15 Last updated: 2015-07-07

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Beijer, KristinaJönsson, MariaBrunström, BjörnBrandt, Ingvar

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