Intracellular accumulation of bilirubin as a defense mechanism against increased oxidative stress
Language English Country France Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22580386
DOI
10.1016/j.biochi.2012.04.026
PII: S0300-9084(12)00175-7
Knihovny.cz E-resources
- MeSH
- Enzyme Activation drug effects MeSH
- Antioxidants metabolism MeSH
- Arsenites pharmacology MeSH
- Bilirubin administration & dosage analogs & derivatives metabolism MeSH
- Hep G2 Cells MeSH
- Heme analysis MeSH
- Heme Oxygenase-1 metabolism MeSH
- Hyperbilirubinemia metabolism MeSH
- Rats MeSH
- Humans MeSH
- Lipopolysaccharides administration & dosage MeSH
- Methemalbumin pharmacology MeSH
- Oxidative Stress drug effects MeSH
- Lipid Peroxidation drug effects MeSH
- Rats, Wistar MeSH
- Sodium Compounds pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antioxidants MeSH
- Arsenites MeSH
- Bilirubin MeSH
- Heme MeSH
- Heme Oxygenase-1 MeSH
- HMOX1 protein, human MeSH Browser
- Lipopolysaccharides MeSH
- Methemalbumin MeSH
- Sodium Compounds MeSH
- sodium arsenite MeSH Browser
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.
References provided by Crossref.org
The Effects of Bilirubin and Lumirubin on Metabolic and Oxidative Stress Markers
Heme Oxygenase-1 May Affect Cell Signalling via Modulation of Ganglioside Composition
Hyperbilirubinemia Protects against Aging-Associated Inflammation and Metabolic Deterioration
