• Je něco špatně v tomto záznamu ?

Widely used pharmaceuticals present in the environment revealed as in vitro antagonists for human estrogen and androgen receptors

M. Ezechiáš, J. Janochová, A. Filipová, Z. Křesinová, T. Cajthaml,

. 2016 ; 152 (-) : 284-91. [pub] 20160312

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc17000344

A considerable amount of scientific evidence indicates that a number of pharmaceuticals that could be detected in the environment can contribute towards the development of problems associated with human reproductive systems, as well as those of wildlife. We investigated the estrogenic and androgenic effects of select pharmaceuticals with high production volume and environmental relevance. We examined the receptor-binding activities of these pharmaceuticals in the T47D human cell line using altered secretion of cytokine CXCL12. Functional yeast-luciferase reporter gene assays were also employed to confirm the mechanism of receptor binding by estrogen and androgen. Non-steroidal anti-inflammatory drugs, namely ibuprofen, diclofenac and antiarrhythmic agent amiodarone showed strong anti-estrogenic effects in the T47D cell line. In the yeast-luciferase assay, these anti-inflammatory drugs also demonstrated anti-estrogenic potency and inhibited the E2 response in a concentration-dependent manner. Amiodarone did not exhibit any response in the yeast-luciferase assay; therefore, the endocrine disruption presumably occurred at a different level without directly involving the receptor. All the anti-inflammatory drugs considered in this study, including ketoprofen, naproxen and clofibrate, exhibited a dose-dependent antagonism towards the androgen receptor in the yeast-luciferase assays. Several other drugs, including the stimulant caffeine, did not show any response in the tests that were employed. A risk assessment analysis using 'Hazard Quotient' suggested a potential risk, especially in the cases of ibuprofen, ketoprofen, diclofenac and clofibrate. The results reveal the intrinsic endocrine disrupting nature of several pharmaceuticals and thus could contribute towards explaining a number of adverse health effects on humans and wildlife.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc17000344
003      
CZ-PrNML
005      
20170117095144.0
007      
ta
008      
170103s2016 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.chemosphere.2016.02.067 $2 doi
024    7_
$a 10.1016/j.chemosphere.2016.02.067 $2 doi
035    __
$a (PubMed)26978704
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Ezechiáš, Martin $u Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic; Institute for Environmental Studies, Faculty of Science, Charles University, Benátská 2, CZ-128 01 Prague 2, Czech Republic.
245    10
$a Widely used pharmaceuticals present in the environment revealed as in vitro antagonists for human estrogen and androgen receptors / $c M. Ezechiáš, J. Janochová, A. Filipová, Z. Křesinová, T. Cajthaml,
520    9_
$a A considerable amount of scientific evidence indicates that a number of pharmaceuticals that could be detected in the environment can contribute towards the development of problems associated with human reproductive systems, as well as those of wildlife. We investigated the estrogenic and androgenic effects of select pharmaceuticals with high production volume and environmental relevance. We examined the receptor-binding activities of these pharmaceuticals in the T47D human cell line using altered secretion of cytokine CXCL12. Functional yeast-luciferase reporter gene assays were also employed to confirm the mechanism of receptor binding by estrogen and androgen. Non-steroidal anti-inflammatory drugs, namely ibuprofen, diclofenac and antiarrhythmic agent amiodarone showed strong anti-estrogenic effects in the T47D cell line. In the yeast-luciferase assay, these anti-inflammatory drugs also demonstrated anti-estrogenic potency and inhibited the E2 response in a concentration-dependent manner. Amiodarone did not exhibit any response in the yeast-luciferase assay; therefore, the endocrine disruption presumably occurred at a different level without directly involving the receptor. All the anti-inflammatory drugs considered in this study, including ketoprofen, naproxen and clofibrate, exhibited a dose-dependent antagonism towards the androgen receptor in the yeast-luciferase assays. Several other drugs, including the stimulant caffeine, did not show any response in the tests that were employed. A risk assessment analysis using 'Hazard Quotient' suggested a potential risk, especially in the cases of ibuprofen, ketoprofen, diclofenac and clofibrate. The results reveal the intrinsic endocrine disrupting nature of several pharmaceuticals and thus could contribute towards explaining a number of adverse health effects on humans and wildlife.
650    _2
$a androgeny $x analýza $x toxicita $7 D000728
650    _2
$a antiflogistika nesteroidní $x analýza $x toxicita $7 D000894
650    _2
$a biotest $x metody $7 D001681
650    _2
$a nádorové buněčné linie $7 D045744
650    _2
$a chemokin CXCL12 $x sekrece $7 D054377
650    _2
$a vztah mezi dávkou a účinkem léčiva $7 D004305
650    _2
$a endokrinní disruptory $x analýza $x toxicita $7 D052244
650    _2
$a estradiol $x toxicita $7 D004958
650    _2
$a antagonisté estrogenu $x analýza $x toxicita $7 D004965
650    _2
$a reportérové geny $7 D017930
650    _2
$a lidé $7 D006801
650    _2
$a luciferasy $x genetika $7 D008156
650    _2
$a léčivé přípravky $x analýza $7 D004364
650    _2
$a androgenní receptory $x metabolismus $7 D011944
650    _2
$a receptory pro estrogeny $x antagonisté a inhibitory $7 D011960
650    _2
$a Saccharomyces cerevisiae $x genetika $7 D012441
650    _2
$a chemické látky znečišťující vodu $x analýza $x toxicita $7 D014874
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Janochová, Jana $u Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic.
700    1_
$a Filipová, Alena $u Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic.
700    1_
$a Křesinová, Zdena $u Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic; Institute for Environmental Studies, Faculty of Science, Charles University, Benátská 2, CZ-128 01 Prague 2, Czech Republic.
700    1_
$a Cajthaml, Tomáš $u Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic; Institute for Environmental Studies, Faculty of Science, Charles University, Benátská 2, CZ-128 01 Prague 2, Czech Republic. Electronic address: cajthaml@biomed.cas.cz.
773    0_
$w MED00002124 $t Chemosphere $x 1879-1298 $g Roč. 152, č. - (2016), s. 284-91
856    41
$u https://pubmed.ncbi.nlm.nih.gov/26978704 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20170103 $b ABA008
991    __
$a 20170117095250 $b ABA008
999    __
$a ok $b bmc $g 1179484 $s 960911
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2016 $b 152 $c - $d 284-91 $e 20160312 $i 1879-1298 $m Chemosphere $n Chemosphere $x MED00002124
LZP    __
$a Pubmed-20170103

Najít záznam

Citační ukazatele

Možnosti archivace