Neuro-inflammatory effects of photodegradative products of bilirubin

Abstract 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 v...

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Autores principales:	J. Jašprová, M Dal Ben, D. Hurný, S. Hwang, K. Žížalová, J. Kotek, R. J. Wong, D. K. Stevenson, S. Gazzin, C. Tiribelli, L. Vítek
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4a4386a8480a497f826de6c002b8fafc
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spelling	oai:doaj.org-article:4a4386a8480a497f826de6c002b8fafc2021-12-02T16:08:15ZNeuro-inflammatory effects of photodegradative products of bilirubin10.1038/s41598-018-25684-22045-2322https://doaj.org/article/4a4386a8480a497f826de6c002b8fafc2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25684-2https://doaj.org/toc/2045-2322Abstract 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.J. JašprováM Dal BenD. HurnýS. HwangK. ŽížalováJ. KotekR. J. WongD. K. StevensonS. GazzinC. TiribelliL. VítekNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q J. Jašprová M Dal Ben D. Hurný S. Hwang K. Žížalová J. Kotek R. J. Wong D. K. Stevenson S. Gazzin C. Tiribelli L. Vítek Neuro-inflammatory effects of photodegradative products of bilirubin
description	Abstract 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.
format	article
author	J. Jašprová M Dal Ben D. Hurný S. Hwang K. Žížalová J. Kotek R. J. Wong D. K. Stevenson S. Gazzin C. Tiribelli L. Vítek
author_facet	J. Jašprová M Dal Ben D. Hurný S. Hwang K. Žížalová J. Kotek R. J. Wong D. K. Stevenson S. Gazzin C. Tiribelli L. Vítek
author_sort	J. Jašprová
title	Neuro-inflammatory effects of photodegradative products of bilirubin
title_short	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_sort	neuro-inflammatory effects of photodegradative products of bilirubin
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/4a4386a8480a497f826de6c002b8fafc
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Neuro-inflammatory effects of photodegradative products of bilirubin

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