Influence of Bilirubin on the Antioxidant Capacity of Plasma in Newborn Infants

Bélanger, Sylvie; Lavoie, Judith; Chessex, Philippe

doi:10.1159/000244422

Cited by 118 publications

(94 citation statements)

References 17 publications

(25 reference statements)

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“…Analysis of the contribution of bilirubin to antioxidant status in neonates has shown that there is a strong correlation between bilirubin levels and total plasma antioxidant activity (Gopinathan et al, 1994). Similarly, other studies in neonates have shown that bilirubin levels that are raised to below toxic levels do not pose any health risk, and may exert a positive effect on total antioxidant power (Belanger et al, 1997).…”

Section: Discussionmentioning

confidence: 96%

Low molecular weight plasma antioxidants and lipid peroxidation in maternal and cord blood

et al. 1999

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Objective: To determine the concentrations of the low molecular weight antioxidants urate, bilirubin, albumin and sulphydryl groups and to measure lipid peroxidation levels in pair-matched maternal and cord blood plasma. Design: Venous blood plasma concentrations of urate, bilirubin, albumin and sulphydryls were determined in healthy pregnant women and in pair matched umbilical cords. The ability of maternal and cord plasma to withstand Cu 2 -induced lipid peroxidation was assessed by measuring the production of thiobarbituric acid reactive substances (TBARS) over time in plasma incubated with Cu 2 . Subjects: Forty healthy women, between 10 and 20 weeks gestation, were recruited randomly from an antenatal clinic. Venous blood samples were obtained from the mothers at the recruitment stage and from the umbilical cords of their newborn after delivery. Results: Urate, bilirubin and sulphydryls were present in signi®cantly higher concentrations (P`0.001) in cord plasma than in maternal plasma. Albumin levels were similar in mothers and cords. Signi®cantly lower levels (P 0.018) of TBARS were produced in cord plasma compared with maternal plasma following incubation with Cu 2 . There were signi®cant correlations between albumin and sulphydryl concentrations in maternal plasma (r 0.43, P 0.007) and between urate concentrations in maternal and cord plasma (r 0.37, P 0.026). Conclusion: Urate, bilirubin and sulphydryls are present in signi®cantly higher concentrations in cord blood than in maternal blood. The increased levels of these antioxidants in cord plasma may contribute to the increased resistance of cord plasma to Cu 2 -induced lipid peroxidation.

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Section: Discussionmentioning

confidence: 96%

Low molecular weight plasma antioxidants and lipid peroxidation in maternal and cord blood

et al. 1999

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“…Conversely, at low concentrations (<1μM), bilirubin has potent anti-oxidant properties, as has been demonstrated in cells, animal models, and in clinical studies [25,47,140,144,[146][147][148]. The mechanism of its antioxidant effects involves effective scavenging of oxidant free radicals by bilirubin/biliverdin redox cycling.…”

Section: A Anti-oxidant and Anti-apoptotic Properties Of Bilirubinmentioning

confidence: 99%

Cerebroprotective Functions of HO-2

Parfenova¹,

Leffler²

2008

CPD

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The constitutive isoform of heme oxygenase, HO-2, is highly expressed in the brain and in cerebral vessels. HO-2 functions in the brain have been evaluated using pharmacological inhibitors of the enzyme and HO-2 gene deletion in in vivo animal models and in cultured cells (neurons, astrocytes, cerebral vascular endothelial cells). Rapid activation of HO-2 via posttranslational modifications without upregulation of HO-2 expression or HO-1 induction coincides with the increase in cerebral blood flow aimed at maintaining brain homeostasis and neuronal survival during seizures, hypoxia, and hypotension. Pharmacological inhibition or gene deletion of brain HO-2 exacerbates oxidative stress induced by seizures, glutamate, and inflammatory cytokines, and causes cerebral vascular injury. Carbon monoxide (CO) and bilirubin, the end products of HO-catalyzed heme degradation, have distinct cytoprotective functions. CO, by binding to a heme prosthetic group, regulates the key components of cell signaling, including BK Ca channels, guanylyl cyclase, NADPH oxidase, and the mitochondria respiratory chain. Cerebral vasodilator effects of CO are mediated via activation of BK Ca channels and guanylyl cyclase. CO, by inhibiting the major components of endogenous oxidantgenerating machinery, NADPH oxidase and the cytochrome C oxidase of the mitochondrial respiratory chain, blocks formation of reactive oxygen species. Bilirubin, via redox cycling with biliverdin, is a potent oxidant scavenger that removes preformed oxidants. Overall, HO-2 has dual housekeeping cerebroprotective functions by maintaining autoregulation of cerebral blood flow aimed at improving neuronal survival in a changing environment, and by providing an effective defense mechanism that blocks oxidant formation and prevents cell death caused by oxidative stress. KeywordsHeme oxygenase; cerebral protection; cerebrovascular disease; oxidative stress; seizures; carbon monoxide; bilirubin Vasodilator role of CO in cerebral circulation A. Vasoactive effects of exogenous CO in cerebral vesselsExperimental studies in newborn pigs conducted using in vivo and in vitro approaches demonstrate that exogenous CO is a potent vasodilator in cerebral circulation [1][2][3][4][5][6][7]. CO can be delivered to the brain as CO gas dissolved in a physiological buffer or as recently introduced CO-releasing molecules (CO-RMs) that release CO on illumination (dimanganese decacarbonyl, DMDC) or when dissolved in physiologically buffered solutions (sodium boranocarbonate, CO-RM-A1) [8,9]. In vivo, CO, DMDC and CORM-A1 applied directly to the brain surface under the cranial window at concentrations ≥10 −7 M causes dilation of pial arterioles, major resistance brain vessels that define the cerebral blood

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“…Bilirubin accounts for the bulk of plasma antioxidant activity (74,75,80). Preterm infants with elevated plasma bilirubin levels suffer from less oxidative-stress injuries (81).…”

Section: Pathophysiologymentioning

confidence: 99%

Neural roles for heme oxygenase: Contrasts to nitric oxide synthase

Barañano

Snyder

2001

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

277

204

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The heme oxygenase (HO) and nitric oxide (NO) synthase (NOS) systems display notable similarities as well as differences. HO and NOS are both oxidative enzymes using NADPH as an electron donor. The constitutive forms of the enzyme are differentially activated, with calcium entry stimulating NOS by binding to calmodulin, whereas calcium entry activates protein kinase C to phosphorylate and activate HO2. Although both NO and carbon monoxide (CO) stimulate soluble guanylyl cyclase to form cGMP, NO also S-nitrosylates selected protein targets. Both involve constitutive and inducible biosynthetic enzymes. However, functions of the inducible forms are virtual opposites. Macrophage-inducible NOS generates NO to kill other cells, whereas HO1 generates bilirubin to exert antioxidant cytoprotective effects and also provides cytoprotection by facilitating iron extrusion from cells. The neuronal form of HO, HO2, is also cytoprotective. Normally, neural NO in the brain seems to exert some sort of behavioral inhibition. However, excess release of NO in response to glutamate's Nmethyl-D-aspartate receptor activation leads to stroke damage. On the other hand, massive neuronal firing during a stroke presumably activates HO2, leading to neuroprotective actions of bilirubin. Loss of this neuroprotection after HO inhibition by mutant forms of amyloid precursor protein may mediate neurotoxicity in Familial Alzheimer's Disease. NO and CO both appear to be neurotransmitters in the brain and peripheral autonomic nervous system. They also are physiologic endothelial-derived relaxing factors for blood vessels. In the gastrointestinal pathway, NO and CO appear to function as coneurotransmitters, both stimulating soluble guanylyl cyclase to cause smooth muscle relaxation.

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Influence of Bilirubin on the Antioxidant Capacity of Plasma in Newborn Infants

Cited by 118 publications

References 17 publications

Low molecular weight plasma antioxidants and lipid peroxidation in maternal and cord blood

Low molecular weight plasma antioxidants and lipid peroxidation in maternal and cord blood

Cerebroprotective Functions of HO-2

Neural roles for heme oxygenase: Contrasts to nitric oxide synthase

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