Please use this identifier to cite or link to this item: https://hdl.handle.net/11499/30147
Title: Caffeine prevents bilirubin-induced cytotoxicity in cultured newborn rat astrocytes
Authors: Deliktaş, Mehmet
Ergin, Hacer
Demiray, Aydın
Akça, Hakan
Özdemir, Özmert M.A.
Özdemir, Mehmet Bülent
Keywords: Bilirubin
caffeine
neurotoxicity
newborn
bilirubin
catalase
cytokine
glutathione
glutathione peroxidase
interleukin 1beta
interleukin 6
malonaldehyde
nitrate
nitrite
superoxide dismutase
toll like receptor
toll like receptor 4
toll like receptor 9
tumor necrosis factor
adenosine receptor blocking agent
animal cell
Article
astrocyte
astrocyte culture
cell viability
controlled study
drug effect
enzyme activity
nervous system inflammation
neuroapoptosis
neuroprotection
nonhuman
priority journal
rat
animal
cell culture
complication
hyperbilirubinemia
preclinical study
toxicity and intoxication
Wistar rat
Animals
Animals, Newborn
Astrocytes
Caffeine
Cells, Cultured
Drug Evaluation, Preclinical
Hyperbilirubinemia
Neurotoxicity Syndromes
Purinergic P1 Receptor Antagonists
Rats, Wistar
Publisher: Taylor and Francis Ltd
Abstract: Objective: Unconjugated bilirubin (UCB) may cause neurotoxicity in preterm neonates due to immaturity of UGT1A1 leading to bilirubin accumulation in the brain. Caffeine used in the treatment of apnea of prematurity was reported to decrease mechanical ventilation requirement, the frequencies of bronchopulmonary dysplasia, patent ductus arteriosus, cerebral palsy and neurodevelopmental disorders in very low birth weight infants. However, the effect of caffeine on hyperbilirubinemia was not yet clarified. Methods: We used astrocyte cell cultures obtained from 2-day-old Wistar albino rats via modified Cole and de Vellis method. UCB concentration toxic to 50% of astrocytes, and caffeine concentration increasing cell viability 100% were used in experiments. While no medication was applied to the control group, UCB (50 µM) and caffeine (100 µM) were applied to the bilirubin and caffeine groups for 24 h. Prophylactic and therapeutic caffeine groups were treated with caffeine 4 h before and after UCB exposure. The effects of caffeine were investigated in rat astrocytes exposed to UCB in terms of cell viability, apoptosis, antioxidant defense, proinflammatory cytokines, and Toll-like receptor (TLR)s. Results: Compared to the control group, UCB increased apoptosis, malondialdehyde (MDA), tumor necrosis factor-? (TNF-?), interleukin (IL)-1ß, IL-6, total nitrate/nitrite, and TLR4 levels, and decreased cell viability, catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) activities, glutathione, and TLR9 levels (for all p <.001). Conversely, prophylactic and therapeutic caffeine improved the detrimental effects of UCB. Conclusions: Caffeine seems encouraging for the prevention and treatment of bilirubin neurotoxicity in rats by means of its antiapoptotic, antioxidant, anti-inflammatory, anti-nitrosative, and anti-TLR-4 properties. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
URI: https://hdl.handle.net/11499/30147
https://doi.org/10.1080/14767058.2017.1419175
ISSN: 1476-7058
Appears in Collections:PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Tıp Fakültesi Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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