Bilirubin: its role in cytoprotection against oxidative stress

Tomaro, Marı́a L.; Batlle, Alcira

doi:10.1016/s1357-2725(01)00130-3

Cited by 135 publications

(85 citation statements)

References 20 publications

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“…The amplification afforded by this antioxidant cycle can readily explain the ability of low concentrations of bilirubin to overcome 10 000-fold higher concentrations of oxidants. Accordingly, the therapeutic potential of exogenously administered bilirubin has been shown in several models of oxidative stress (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

Protection Against Ischemia/Reperfusion Injury in Cardiac and Renal Transplantation with Carbon Monoxide, Biliverdin and Both

Nakao¹,

Neto²,

Kanno³

et al. 2005

American Journal of Transplantation

214

158

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Both carbon monoxide (CO) and biliverdin, products of heme degradation by heme oxygenase, have been shown to attenuate ischemia/reperfusion (I/R) injury. We hypothesized in this study that dual-treatment with CO and biliverdin would induce enhanced protective effects against cold I/R injury. Heterotopic heart and orthotopic kidney transplantation were performed in syngeneic Lewis rats after 24-h cold preservation in UW solution. While monotherapy with CO (20 ppm) or biliverdin (50 mg/kg, ip) did not alter the survival of heart grafts, dual-treatment increased survival to 80% from 0% in untreated recipients, with a significant decrease of myocardial injury and improved cardiac function. Similarly, dual-treatment significantly improved glomerular filtration rates of renal grafts and prolonged recipient survival compared to untreated controls. I/R injury-induced up-regulation of pro-inflammatory mediators (e.g. TNF-a , iNOS) and extravasation of inflammatory infiltrates were significantly less with dual-treatment than untreated controls. In addition, dual-treatment was effective in decreasing lipid peroxidation and improving graft blood flow through the distinctive action of biliverdin and CO, respectively. The study shows that the addition of byproducts of heme degradation with different mechanisms of action provides enhanced protection against transplant-associated cold I/R injury of heart and kidney grafts.

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Section: Discussionmentioning

confidence: 99%

Protection Against Ischemia/Reperfusion Injury in Cardiac and Renal Transplantation with Carbon Monoxide, Biliverdin and Both

Nakao¹,

Neto²,

Kanno³

et al. 2005

American Journal of Transplantation

214

158

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“…These findings may indicate that bilirubin levels appear to be depleted due to exposure to reactive oxidative species, such as those derived from cigarette smoking [72,76]. The degradation of haem to biliverdin by haem-oxygenase (HO), where the production of bilirubin originates, results in biliverdin being subsequently reduced to bilirubin by biliverdin reductase [77]. Moreover, HO-1, the inducible isoform of HO, upregulated by oxidative stress [78], is expressed increasingly in hypoxia and in type II pneumocytes and alveolar macrophages within the lung [79].…”

Section: Lung Function Abnormalities In Liver Diseasesmentioning

confidence: 99%

Inflammatory bowel diseases, chronic liver diseases and the lung

Rodríguez-Roisin

Bartolome

Huchon³

et al. 2016

Eur Respir J

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This review is devoted to the distinct associations of inflammatory bowel diseases (IBD) and chronic liver disorders with chronic airway diseases, namely chronic obstructive pulmonary disease and bronchial asthma, and other chronic respiratory disorders in the adult population. While there is strong evidence for the association of chronic airway diseases with IBD, the data are much weaker for the interplay between lung and liver multimorbidities. The association of IBD, encompassing Crohn's disease and ulcerative colitis, with pulmonary disorders is underlined by their heterogeneous respiratory manifestations and impact on chronic airway diseases. The potential relationship between the two most prevalent liver-induced pulmonary vascular entities, i.e. portopulmonary hypertension and hepatopulmonary syndrome, and also between liver disease and other chronic respiratory diseases is also approached. Abnormal lung function tests in liver diseases are described and the role of increased serum bilirubin levels on chronic respiratory problems are considered. @ERSpublications Lung-gut cross-talk: the association of IBD with respiratory multimorbitidies, including COPD and bronchial asthma

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“…Both in vitro and in vivo, UCB at low unbound concentrations (B f ) is a potent antioxidant that protects against damage from a wide range of oxidant agents (1)(2)(3). At B f modestly above its aqueous saturation (70 nM), however, in vitro exposure of astrocytes and neurons to UCB rapidly impairs a variety of cellular functions (4).…”

mentioning

confidence: 99%

Bilirubin protects astrocytes from its own toxicity by inducing up-regulation and translocation of multidrug resistance-associated protein 1 (Mrp1)

Gennuso

Fernetti

Tirolo

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

144

128

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Unconjugated bilirubin (UCB) causes encephalopathy in severely jaundiced neonates by damaging astrocytes and neurons. Astrocytes, which help defend the brain against cytotoxic insults, express the ATP-dependent transporter, multidrug resistance-associated protein 1 (Mrp1), which mediates export of organic anions, probably including UCB. We therefore studied whether exposure to UCB affects the expression and intracellular localization of Mrp1 in cultured mouse astroglial cells (>95% astrocytes). Mrp1 was localized and quantitated by confocal laser scanning microscopy and double immunofluorescence labeling by using specific antibodies against Mrp1 and the astrocyte marker glial fibrillary acidic protein, plus the Golgi marker wheat germ agglutinin (WGA). In unexposed astrocytes, Mrp1 colocalized with WGA in the Golgi apparatus. Exposure to UCB at a low unbound concentration (B f) of 40 nM caused rapid redistribution of Mrp1 from the Golgi throughout the cytoplasm to the plasma membrane, with a peak 5-fold increase in Mrp1 immunofluorescence intensity from 30 to 120 min. B f above aqueous saturation produced a similar but aborted response. Exposure to this higher B f for 16 h markedly decreased Trypan blue exclusion and methylthiazoletetrazoilum activity and increased apoptosis 5-fold by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay. These toxic effects were modestly increased by inhibition of Mrp1 activity with 3-([3-(2-[7-chloro-2-quinolinyl]ethenyl)phenyl-(3-dimethylamino-3-oxopropyl)-thio-methyl]thio)propanoic acid (MK571). By contrast, B f ‫؍‬ 40 nM caused injury only if Mrp1 activity was inhibited by MK571, which also blocked translocation of Mrp1. Our conclusion is that in astrocytes, UCB up-regulates expression of Mrp1 and promotes its trafficking from the Golgi to the plasma membrane, thus moderating cytotoxicity from UCB, presumably by limiting its intracellular accumulation.

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Bilirubin: its role in cytoprotection against oxidative stress

Cited by 135 publications

References 20 publications

Protection Against Ischemia/Reperfusion Injury in Cardiac and Renal Transplantation with Carbon Monoxide, Biliverdin and Both

Protection Against Ischemia/Reperfusion Injury in Cardiac and Renal Transplantation with Carbon Monoxide, Biliverdin and Both

Inflammatory bowel diseases, chronic liver diseases and the lung

Bilirubin protects astrocytes from its own toxicity by inducing up-regulation and translocation of multidrug resistance-associated protein 1 (Mrp1)

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