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Neuro-inflammatory effects of photodegradative products of bilirubin

Phototherapy was introduced in the early 1950’s, and is the primary treatment of severe neonatal jaundice or Crigler-Najjar syndrome. Nevertheless, the potential biological effects of the products generated from the photodegradation of bilirubin during phototherapy remain unknown. This is very relev...

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Autores principales: Jašprová, J., Dal Ben, M, Hurný, D., Hwang, S., Žížalová, K., Kotek, J., Wong, R. J., Stevenson, D. K., Gazzin, S., Tiribelli, C., Vítek, L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945592/
https://www.ncbi.nlm.nih.gov/pubmed/29748620
http://dx.doi.org/10.1038/s41598-018-25684-2
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author Jašprová, J.
Dal Ben, M
Hurný, D.
Hwang, S.
Žížalová, K.
Kotek, J.
Wong, R. J.
Stevenson, D. K.
Gazzin, S.
Tiribelli, C.
Vítek, L.
author_facet Jašprová, J.
Dal Ben, M
Hurný, D.
Hwang, S.
Žížalová, K.
Kotek, J.
Wong, R. J.
Stevenson, D. K.
Gazzin, S.
Tiribelli, C.
Vítek, L.
author_sort Jašprová, J.
collection PubMed
description Phototherapy was introduced in the early 1950’s, and is the primary treatment of severe neonatal jaundice or Crigler-Najjar syndrome. Nevertheless, the potential biological effects of the products generated from the photodegradation of bilirubin during phototherapy remain unknown. This is very relevant in light of recent clinical observations demonstrating that the use of aggressive phototherapy can increase morbidity or even mortality, in extremely low birthweight (ELBW) infants. The aim of our study was to investigate the effects of bilirubin, lumirubin (LR, its major photo-oxidative product), and BOX A and B (its monopyrrolic oxidative products) on the central nervous system (CNS) using in vitro and ex vivo experimental models. The effects of bilirubin photoproducts on cell viability and expression of selected genes were tested in human fibroblasts, three human CNS cell lines (neuroblastoma SH-SY5Y, microglial HMC3, and glioblastoma U-87 cell lines), and organotypic rat hippocampal slices. Neither bilirubin nor its photo-oxidative products affected cell viability in any of our models. In contrast, LR in biologically-relevant concentrations (25 μM) significantly increased gene expression of several pro-inflammatory genes as well as production of TNF-α in organotypic rat hippocampal slices. These findings might underlie the adverse outcomes observed in ELBW infants undergoing aggressive phototherapy.
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spelling pubmed-59455922018-05-14 Neuro-inflammatory effects of photodegradative products of bilirubin Jašprová, J. Dal Ben, M Hurný, D. Hwang, S. Žížalová, K. Kotek, J. Wong, R. J. Stevenson, D. K. Gazzin, S. Tiribelli, C. Vítek, L. Sci Rep Article Phototherapy was introduced in the early 1950’s, and is the primary treatment of severe neonatal jaundice or Crigler-Najjar syndrome. Nevertheless, the potential biological effects of the products generated from the photodegradation of bilirubin during phototherapy remain unknown. This is very relevant in light of recent clinical observations demonstrating that the use of aggressive phototherapy can increase morbidity or even mortality, in extremely low birthweight (ELBW) infants. The aim of our study was to investigate the effects of bilirubin, lumirubin (LR, its major photo-oxidative product), and BOX A and B (its monopyrrolic oxidative products) on the central nervous system (CNS) using in vitro and ex vivo experimental models. The effects of bilirubin photoproducts on cell viability and expression of selected genes were tested in human fibroblasts, three human CNS cell lines (neuroblastoma SH-SY5Y, microglial HMC3, and glioblastoma U-87 cell lines), and organotypic rat hippocampal slices. Neither bilirubin nor its photo-oxidative products affected cell viability in any of our models. In contrast, LR in biologically-relevant concentrations (25 μM) significantly increased gene expression of several pro-inflammatory genes as well as production of TNF-α in organotypic rat hippocampal slices. These findings might underlie the adverse outcomes observed in ELBW infants undergoing aggressive phototherapy. Nature Publishing Group UK 2018-05-10 /pmc/articles/PMC5945592/ /pubmed/29748620 http://dx.doi.org/10.1038/s41598-018-25684-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jašprová, J.
Dal Ben, M
Hurný, D.
Hwang, S.
Žížalová, K.
Kotek, J.
Wong, R. J.
Stevenson, D. K.
Gazzin, S.
Tiribelli, C.
Vítek, L.
Neuro-inflammatory effects of photodegradative products of bilirubin
title Neuro-inflammatory effects of photodegradative products of bilirubin
title_full Neuro-inflammatory effects of photodegradative products of bilirubin
title_fullStr Neuro-inflammatory effects of photodegradative products of bilirubin
title_full_unstemmed Neuro-inflammatory effects of photodegradative products of bilirubin
title_short Neuro-inflammatory effects of photodegradative products of bilirubin
title_sort neuro-inflammatory effects of photodegradative products of bilirubin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945592/
https://www.ncbi.nlm.nih.gov/pubmed/29748620
http://dx.doi.org/10.1038/s41598-018-25684-2
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