Nejvíce citovaný článek - PubMed ID 28495428
Cytotoxic bilirubin metabolites overlooked so far
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.
- MeSH
- bilirubin analogy a deriváty imunologie MeSH
- buněčné linie MeSH
- fotolýza MeSH
- fototerapie škodlivé účinky MeSH
- hipokampus imunologie patologie MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- novorozenec MeSH
- novorozenecká žloutenka terapie MeSH
- potkani Wistar MeSH
- TNF-alfa imunologie MeSH
- viabilita buněk MeSH
- zánět imunologie patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- novorozenec MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- bilirubin MeSH
- lumirubin MeSH Prohlížeč
- TNF-alfa MeSH