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Intracellular accumulation of bilirubin as a defense mechanism against increased oxidative stress
Jaroslav Zelenka, Lucie Muchova, Miroslava Zelenkova, Katerina Vanova, Hendrik J. Vreman, Ronald J. Wong, Libor Vitek
Jazyk angličtina Země Francie
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
NT11327
MZ0
CEP - Centrální evidence projektů
- MeSH
- aktivace enzymů účinky léků MeSH
- antioxidancia metabolismus MeSH
- arsenitany farmakologie MeSH
- bilirubin aplikace a dávkování analogy a deriváty metabolismus MeSH
- buňky Hep G2 MeSH
- hem analýza MeSH
- hemoxygenasa-1 metabolismus MeSH
- hyperbilirubinemie metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- lipopolysacharidy aplikace a dávkování MeSH
- methemalbumin farmakologie MeSH
- oxidační stres účinky léků MeSH
- peroxidace lipidů účinky léků MeSH
- potkani Wistar MeSH
- sloučeniny sodíku farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Antioxidant, anti-inflammatory and anti-atherogenic effects have been associated with elevations of unconjugated bilirubin (UCB) in serum and with the induction of heme oxygenase-1 (HO-1), the rate-limiting enzyme in UCB synthesis. The aim of this study was to investigate the intracellular metabolism and antioxidant properties of UCB in human hepatoblastoma HepG2 cells and tissues of Wistar rats exposed to oxidative stressors and lipopolysaccharide (LPS), respectively. Intracellular UCB concentrations in HepG2 cells correlated with its levels in culture media (p < 0.001) and diminished lipid peroxidation in a dose-dependent manner (p < 0.001). Moreover, induction of HO-1 with sodium arsenite led to 2.4-fold (p = 0.01) accumulation of intracellular UCB over basal level while sodium azide-derived oxidative stress resulted in a 60% drop (p < 0.001). This decrease was ameliorated by UCB elevation in media or by simultaneous induction of HO-1. In addition, hyperbilirubinemia and liver HO-1 induction in LPS-treated rats resulted in a 2-fold accumulation of tissue UCB (p = 0.01) associated with enhanced protection against lipid peroxidation (p = 0.02). In conclusion, hyperbilirubinemia and HO-1 induction associated with inflammation and oxidative stress increase intracellular concentrations of UCB, thus enhancing the protection of cellular lipids against peroxidation. Therefore, the previously reported protective effects of hyperbilirubinemia and HO-1 induction are at least in part due to intracellular accumulation of UCB.
4th Department of Internal Medicine 1st Faculty of Medicine Charles University Prague Czech Republic
Department of Pediatrics Stanford University School of Medicine Stanford CA USA
Institute of Physiology Academy of Sciences Dept 75 Prague Czech Republic
Citace poskytuje Crossref.org
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- $a Antioxidant, anti-inflammatory and anti-atherogenic effects have been associated with elevations of unconjugated bilirubin (UCB) in serum and with the induction of heme oxygenase-1 (HO-1), the rate-limiting enzyme in UCB synthesis. The aim of this study was to investigate the intracellular metabolism and antioxidant properties of UCB in human hepatoblastoma HepG2 cells and tissues of Wistar rats exposed to oxidative stressors and lipopolysaccharide (LPS), respectively. Intracellular UCB concentrations in HepG2 cells correlated with its levels in culture media (p < 0.001) and diminished lipid peroxidation in a dose-dependent manner (p < 0.001). Moreover, induction of HO-1 with sodium arsenite led to 2.4-fold (p = 0.01) accumulation of intracellular UCB over basal level while sodium azide-derived oxidative stress resulted in a 60% drop (p < 0.001). This decrease was ameliorated by UCB elevation in media or by simultaneous induction of HO-1. In addition, hyperbilirubinemia and liver HO-1 induction in LPS-treated rats resulted in a 2-fold accumulation of tissue UCB (p = 0.01) associated with enhanced protection against lipid peroxidation (p = 0.02). In conclusion, hyperbilirubinemia and HO-1 induction associated with inflammation and oxidative stress increase intracellular concentrations of UCB, thus enhancing the protection of cellular lipids against peroxidation. Therefore, the previously reported protective effects of hyperbilirubinemia and HO-1 induction are at least in part due to intracellular accumulation of UCB.
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