1 Ocak 2021 Dergi makalesi Açık Erişim

Hogberg, Helena T.; da Silveira E Sa, Rita de Cassia; Kleensang, Andre; Bouhifd, Mounir; Cemiloglu Ulker, Ozge; Smirnova, Lena; Behl, Mamta; Maertens, Alexandra; Zhao, Liang; Hartung, Thomas

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  <dc:creator>Hogberg, Helena T.</dc:creator>
  <dc:creator>da Silveira E Sa, Rita de Cassia</dc:creator>
  <dc:creator>Kleensang, Andre</dc:creator>
  <dc:creator>Bouhifd, Mounir</dc:creator>
  <dc:creator>Cemiloglu Ulker, Ozge</dc:creator>
  <dc:creator>Smirnova, Lena</dc:creator>
  <dc:creator>Behl, Mamta</dc:creator>
  <dc:creator>Maertens, Alexandra</dc:creator>
  <dc:creator>Zhao, Liang</dc:creator>
  <dc:creator>Hartung, Thomas</dc:creator>
  <dc:date>2021-01-01</dc:date>
  <dc:description>Due to regulatory bans and voluntary substitutions, halogenated polybrominated diphenyl ether (PBDE) flame retardants (FR) are increasingly substituted by mainly organophosphorus FR (OPFR). Leveraging a 3D rat primary neural organotypic in vitro model (rat brainsphere), we compare developmental neurotoxic effects of BDE-47-the most abundant PBDE congener-with four OPFR (isopropylated phenyl phosphate-IPP, triphenyl phosphate-TPHP, isodecyl diphenyl phosphate-IDDP, and tricresyl phosphate (also known as trimethyl phenyl phosphate)-TMPP). Employing mass spectroscopy-based metabolomics and transcriptomics, we observe at similar human-relevant non-cytotoxic concentrations (0.1-5 mu M) stronger developmental neurotoxic effects by OPFR. This includes toxicity to neurons in the low mu M range; all FR decrease the neurotransmitters glutamate and GABA (except BDE-47 and TPHP). Furthermore,n-acetyl aspartate (NAA), considered a neurologic diagnostic molecule, was decreased by all OPFR. At similar concentrations, the FR currently in use decreased plasma membrane dopamine active transporter expression, while BDE-47 did not. Several findings suggest astrogliosis induced by the OPFR, but not BDE-47. At the 5 mu M concentrations, the OPFR more than BDE-47 interfered with myelination. An increase of cytokine gene and receptor expressions suggests that exposure to OPFR may induce an inflammatory response. Pathway/category overrepresentation shows disruption in 1) transmission of action potentials, cell-cell signaling, synaptic transmission, receptor signaling, (2) immune response, inflammation, defense response, (3) cell cycle and (4) lipids metabolism and transportation. Taken together, this appears to be a case of regretful substitution with substances not less developmentally neurotoxic in a primary rat 3D model.</dc:description>
  <dc:identifier>https://aperta.ulakbim.gov.trrecord/3667</dc:identifier>
  <dc:identifier>oai:zenodo.org:3667</dc:identifier>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>http://www.opendefinition.org/licenses/cc-by</dc:rights>
  <dc:source>ARCHIVES OF TOXICOLOGY 95(1) 207-228</dc:source>
  <dc:title>Organophosphorus flame retardants are developmental neurotoxicants in a rat primary brainsphere in vitro model</dc:title>
  <dc:type>info:eu-repo/semantics/article</dc:type>
  <dc:type>publication-article</dc:type>
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