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From:
Kate Hallberg <[log in to unmask]>
Reply To:
Lactation Information and Discussion <[log in to unmask]>
Date:
Thu, 10 Oct 1996 13:06:42 -0600
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Date: Thu, 10 Oct 1996 13:02:57 -0600
To: Kate Hallberg <[log in to unmask]>
From: Kate Hallberg <[log in to unmask]>
Subject: bilirubin and free radical scavenging

Jaundice….

*****ARCHIVES INTERNATIONALES DE PHYSIOLOGIE ET DE BIOCHIMIE*****

(REFERENCE 1 OF 23)
74021242

Bonnett R  Stewart JC
On the photo-oxidation of bilirubin in methanol.

In: Arch Int Physiol Biochim (1972 Dec) 80(5):951-2

[No Abstract Available]

*****BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS*****

(REFERENCE 2 OF 23)
95398622

Yamaguchi T  Horio F  Hashizume T  Tanaka M  Ikeda S  Kakinuma A
  Nakajima H
Bilirubin is oxidized in rats treated with endotoxin and acts as a
  physiological antioxidant synergistically with ascorbic acid in vivo.

In: Biochem Biophys Res Commun (1995 Sep 5) 214(1):11-9

We examined the possibility that bilirubin physiologically acts as an
  antioxidant by using scurvy-prone ODS-od/od rats treated with
  endotoxin (lipopolysaccharide: LPS). Recently, bilirubin oxidative
  metabolites were isolated from human urine and named biotripyrrin-a
  and biotripyrrin-b. The LPS injection markedly increased bilirubin
  oxidative metabolites in urine of rats fed an ascorbic acid-free
  diet. This increase was supressed by feeding an adequate amount of
  ascorbic acid, a physiological antioxidant. the concentrations of
  biotripyrrin-a and -b in urine collected 6.5-10 h after the LPS
  injection were lower in rats fed an ascorbic acid-supplemented diet
  than in rats fed an ascorbic acid-free diet. Moreover, feeding with
  ascorbic acid suppressed the elevation of hepatic mRNA level of heme
  oxygenase-1, the rate-limiting enzyme of bilirubin biosynthesis, in
  rats injected with LPS. These findings suggest that bilirubin is
  oxidized in rats treated with LPS and acts as a physiological
  antioxidant synergistically with ascorbic acid in vivo.

Institutional address:
     Department of Biochemical Genetics
     Tokyo Medical and Dental University
     Japan.

*****BIOCHEMISTRY AND CELL BIOLOGY*****

(REFERENCE 3 OF 23)
92189753

Wu TW  Wu J  Li RK  Mickle D  Carey D
Albumin-bound bilirubins protect human ventricular myocytes against
  oxyradical damage.

In: Biochem Cell Biol (1991 Oct-Nov) 69(10-11):683-8

Synthetic delta-bilirubin (i.e., bilirubin that is covalently bonded
  to albumin) and, to a lesser extent, bilirubin that is physically
  adsorbed to albumin substantially prolonged the survival of human
  ventricular myocytes against in situ generated oxyradicals. This
  cytoprotection, manifested at micromolar concentrations of either
  form of bilirubin, surpasses those given by unconjugated bilirubin
  alone, by equimolar levels of albumin (which has some cytoprotective
  activity), by known antioxidants ascorbate, mannitol, or Trolox, and
  by oxyradical scavenging enzymes superoxide dismutase (24,200 IU/L)
  plus catalase (92,000 IU/L) on the same cells. Our human cell-based
  data provide the first direct evidence that albumin-bound bilirubins,
  especially delta bilirubin, are potent circulating cytoprotectors.
  The latter may be important in defending, among others, the
  myocardium, which is much less equipped in antioxidant defences than
  for example the liver or intestines.

Institutional address:
     Department of Clinical Biochemistry
     University of Toronto
     Ont.
     Canada.

*****BIOCHEMICAL PHARMACOLOGY*****

(REFERENCE 4 OF 23)
96182782

Wu TW  Fung KP  Wu J  Yang CC  Weisel RD
Antioxidation of human low density lipoprotein by unconjugated and
  conjugated bilirubins.

In: Biochem Pharmacol (1996 Mar 22) 51(6):859-62

We demonstrate here that both unconjugated bilirubin (Bu) and
  conjugated bilirubin (Bc) can protect human low density
  lipoprotein(LDL) against oxidation by oxyradicals generated by 2,2'-
  azo-bis (2 amidinopropane) dihydrochloride at 37 degrees. The
  oxidation was assessed by agarose gel electrophoresis and was further
  corroborated by assaying the malondialdehydes and lipid peroxides
  formed throughout oxidation. On a per mole basis, Bu and less so Bc
  was more effective than ascorbate in preventing LDL oxidation. Since
  oxidative modification of human LDL was implicated in plaque
  formation in blood vessels leading to atherogenesis, the data
  suggested that either bile pigment may help reduce the risk of
  atherogenesis.

Institutional address:
     Department of Clinical Biochemistry and Surgery
     University of Toronto
     Ontario
     Canada.

*****BIOCHIMICA ET BIOPHYSICA ACTA*****

(REFERENCE 5 OF 23)
91159454

Kwak JY  Takeshige K  Cheung BS  Minakami S
Bilirubin inhibits the activation of superoxide-producing NADPH
  oxidase in a neutrophil cell-free system.

In: Biochim Biophys Acta (1991 Feb 15) 1076(3):369-73

We studied the effect of bilirubin on the NADPH-dependent superoxide
  production induced by sodium dodecyl sulfate in a cell-free system
  consisting of the membrane and cytosolic fractions of pig
  neutrophils. Preincubation of the cytosolic fraction with bilirubin
  before the addition of sodium dodecyl sulfate resulted in the time-
  and dose-dependent inhibition of the superoxide production while the
  preincubation of the membrane fraction with the tetrapyrrole did not
  result in the inhibition. When the pigment was added after the
  initiation of the reaction, the ongoing production was not affected
  by the addition. Other tetrapyrroles, such as hemin, protoporphyrin
  and biliverdin, also inhibited the production. The results indicate
  that bilirubin inhibits the activation process of the superoxide
  producing NADPH oxidase by decreasing the potency of the cytosolic
  fraction and its inhibitory effect seems to be due to the hydrophobic
  nature of the tetrapyrrole.

Institutional address:
     Department of Biochemistry
     Kyushu University School of Medicine
     Fukuoka
     Japan.

(REFERENCE 6 OF 23)
96085104

Hulea SA  Wasowicz E  Kummerow FA
Inhibition of metal-catalyzed oxidation of low-density lipoprotein by
  free and albumin-bound bilirubin.

In: Biochim Biophys Acta (1995 Oct 26) 1259(1):29-38

Both free and albumin-bound bilirubin are known to scavenge peroxyl
  radicals in vitro. In the present work we showed that free and
  albumin-bound bilirubin at the physiological concentration of the
  bile pigment in blood plasma could greatly inhibit the metal-
  catalyzed oxidation of low density lipoprotein (LDL) as shown by the
  reduced thiobarbituric acid reactivity, smaller or no shifts in
  electrophoretic mobility, less apo B fragmentation and a decreased
  amount of cholesterol oxidation products as detected by gas
  chromatography. Free bilirubin (BR) was more effective in inhibiting
  the production of thiobarbituric acid reactive substances in iron-
  catalyzed LDL peroxidation as compared to the copper-catalyzed
  reaction up to a BR to metal molar ratio of 4:1. Above this ratio the
  same degree of inhibition was observed for both metal ions. It was
  found that serum albumin provided full protection against Cu(2+)-
  dependent oxidative stress only at very high protein to metal molar
  ratio, i.e., 30:1, that is similar to that in human plasma.
  Complexation of BR to albumin brought about a marked increase in the
  capacity of the complex to bind metal ions, particularly iron, as
  opposed to albumin alone. At a molar ratio of metal ion to albumin-BR
  of 1:1 the inhibition of lipid peroxidation was about 96% and it was
  almost complete at a molar ratio of 1:2. The ability of albumin-BR
  complex to inhibit effectively the transition metals-dependent
  oxidative stress could be important in the extravascular space where
  local concentrations of metal ions may exceed the protein binding
  capacity. In addition, the strong binding of iron to the albumin-BRcomplex
may be clinically important, especially in iron loaded sera
  of hemochromatosis patients, where the transferrin is fully saturated
  with this ion and the free iron could catalyze lipid peroxidation
  unless bound by a metal trapping device such as the albumin-BR
  complex.

Institutional address:
     University of Illinois
     Department of Food Science
     Burnsides Research Laboratory
     Urbana 61801
     USA.


*****CELL BIOLOGY INTERNATIONAL REPORTS*****

(REFERENCE 7 OF 23)
93008294

Chen LX  Lu JF  Wang K
The influence of bilirubin on fluidity and rotational correlation
  times of human erythrocyte membrane.

In: Cell Biol Int Rep (1992 Jun) 16(6):567-73

The effects of bilirubin on the membrane motion parameters of human
  erythrocyte membrane were determined by the spin labelled ESR method.
  It causes a decrease in the order parameter and an increase in the
  corresponding fluidity of the lipid molecules. Bovine serum albumin
  was found to inhibit effectively the effects due to bilirubin. The
  disturbance to the organization of membrane molecules by bilirubin as
  well as the protective effects of serum albumin are discussed on the
  basis of the experimental results.

Institutional address:
     National Laboratory of Natural and Biomimetic Drugs
     Beijing Medical University
     China.

*****EXPERIENTIA*****

(REFERENCE 8 OF 23)
90127285

Ribo JM  Farrera JA  Claret J
Proton-induced dismutation of superoxide in aprotic media by bile
  pigments.

In: Experientia (1990 Jan 15) 46(1):63-7

Cyclic voltammetry of molecular oxygen in aprotic media
  (dimethylformamide) and in the presence of bilirubin and other bile
  pigments shows that superoxide anion (O2-.) undergoes proton-induced
  dismutation. Lactam hydrogens of bile pigments are sufficiently acid
  to induce (O2-.) disproportionation to O2 and H2O2. Because of its
  characteristic lipophilic behavior, a biological role for natural
  bilirubin similar to that of other non-enzymatic lipophilic
  scavengers of (O2-.) is suggested.

Institutional address:
     Departament de Quimica Organica
     Universitat de Barcelona
     Spain.

*****FEBS LETTERS*****

(REFERENCE 9 OF 23)
93387484

Neuzil J  Stocker R
Bilirubin attenuates radical-mediated damage to serum albumin.

In: FEBS Lett (1993 Oct 4) 331(3):281-4

Oxidative damage to biological macromolecules has been implicated in
  a number of diseases. Much interest has focused on how non-
  proteinaceous, low-molecular weight antioxidants prevent oxidative
  damage to lipids, while comparatively little is known about protein
  antioxidation. Here we show that bilirubin (BR), the end-product of
  heme catabolism, when bound to bovine serum albumin (BSA), is
  oxidised by hydroxyl (.OH), hydroperoxyl (HO2.), and superoxide anion
  (O2-.) radicals to so far mostly uncharacterised products. The
  initial oxidation rates of BSA-bound BR decreased in the order OH >
  HO2. > O2-.. BR protected its carrier protein from oxidative damage
  inflicted by .OH radicals. This protective action included a
  reduction in the .OH-mediated cleavage of BSA, conversion of Trp into
  kynurenine and formation of 'bityrosine-specific' fluorescence. BR
  also strongly inhibited .OH-mediated formation of protein carbonyls,
  whereas ascorbate and Trolox (a water-soluble analogue of vitamin E)
  were much less effective. These results support an antioxidant-
  protective function of BR and point towards significant differences
  in the efficacies of various antioxidants in the prevention of
  oxidative damage to lipids and proteins.

Institutional address:
     Biochemistry Group
     Heart Research Institute
     Sydney
     NSW

*****FREE RADICAL BIOLOGY AND MEDICINE*****

(REFERENCE 10 OF 23)
93093494

Kazui M  Andreoni KA  Norris EJ  Klein AS  Burdick JF  Beattie C
  Sehnert SS  Bell WR  Bulkley GB  Risby TH
Breath ethane: a specific indicator of free-radical-mediated lipid
  peroxidation following reperfusion of the ischemic liver.

In: Free Radic Biol Med (1992 Nov) 13(5):509-15

A major component of the organ injury mediated by toxic oxidants,
  such as seen following reperfusion of the ischemic liver, is due to
  the peroxidation of polyunsaturated fatty acids, especially of cell
  membranes. We utilized the measurement of exhaled breath ethane, a
  metabolic product unique to oxidant-mediated lipid peroxidation, as a
  noninvasive indicator of this process in swine liver subjected to
  warm ischemia/reperfusion. Under rigorously controlled anesthesia
  conditions, pig livers were subjected to 2 h of warm total ischemia,
  followed by reperfusion in situ. Expired air was collected and its
  ethane content quantitated by a novel gas chromatographic technique.
  The time course of breath ethane generation correlated closely with
  the appearance of hepatocellular injury as measured by impairment of
  Factor VII generation and other measures of liver integrity.
  Moreover, the administration of the specific superoxide free radical
  scavenger, superoxide dismutase (SOD), significantly attenuated both
  the elaboration of ethane and the hepatocellular injury. These
  findings not only provide confirmation of the previously reported
  link between hepatocellular injury by free radicals generated at
  reperfusion, but also establish the use of expired breath ethane
  analysis as a sensitive, specific, and noninvasive indicator of the
  injury process in real time.
Institutional address:
     Department of Surgery
     Johns Hopkins Medical Institutions
     Baltimore
     MD 21287.

*****JOURNAL OF BIOLOGICAL CHEMISTRY*****

(REFERENCE 11 OF 23)
95197595

Bowry VW  Mohr D  Cleary J  Stocker R
Prevention of tocopherol-mediated peroxidation in ubiquinol-10-free
  human low density lipoprotein.

In: J Biol Chem (1995 Mar 17) 270(11):5756-63

Oxidation of low density lipoprotein (LDL) may be involved in the
  development of atherosclerosis. It has recently been shown that alpha-
  tocopherol (alpha-TOH) can act either as an antioxidant or prooxidant
  for isolated low density lipoprotein (LDL). In the absence of an
  effective co-antioxidant, alpha-TOH is a prooxidant and this activity
  is evidently due to reaction of the alpha-tocopheroxyl radical (alpha-
  TO.) with the LDL's polyunsaturated lipids (Bowry, V. B., and
  Stocker, R. (1993) J. Am. Chem. Soc. 115, 6029-6045). Herein we
  examined the effectiveness of selected natural and synthetic radical
  scavengers as co-antioxidants for inhibiting peroxyl radical-induced
  peroxidation in LDL that is devoid of ubiquinol-10 (an effective
  endogenous co-antioxidant) but still contains most of its natural
  complement of alpha-TOH. Various quinols, catechols, and
  aminophenols, as well as ascorbate, 6-palmityl ascorbate, and
  bilirubin, were very effective co-antioxidants under our test
  conditions, whereas ordinary phenolic antioxidants, including short-
  tailed alpha-TOH homologues, were less effective. Reduced
  glutathione, urate, and Probucol were ineffective. These findings
  confirm that the prooxidant activity of alpha-TOH in LDL relies
  heavily on the segregation of water-insoluble radicals (particularly
  alpha-TO.) into individual LDL particles, since it was those
  compounds that are expected to either irreversibly reduce alpha-TO. or
accelerate the diffusion of radicals between particles which most
  effectively inhibited the tocopherol-mediated phase of peroxidation.
  Theoretical and practical implications of these findings are
  discussed, as is their relevance to the "LDL oxidation" hypothesis of
  atherogenesis.

Institutional address:
     Biochemistry Group
     Heart Research Institute
     Sydney
     New South Wales
     Australia.

(REFERENCE 12 OF 23)
94266886

Neuzil J  Stocker R
Free and albumin-bound bilirubin are efficient co-antioxidants for
  alpha-tocopherol, inhibiting plasma and low density lipoprotein lipid
  peroxidation.

In: J Biol Chem (1994 Jun 17) 269(24):16712-9

Peroxidation of the lipid moieties of low density lipoproteins (LDL)
  is regarded as an early event in atherogenesis. Because bilirubin is
  a physiological reductant with antioxidant activities, we
  investigated its inhibitory action on the radical-mediated oxidation
  of LDL and plasma lipids. Exposing fresh human blood plasma to
  lipophilic peroxyl radicals generated from 2,2'-azobis(2,4-
  dimethylvaleronitrile) (AMVN) resulted in rapid oxidation of
  ubiquinol-10, followed by that of ascorbate and bilirubin. Plasma
  lipids were well protected from peroxidation as long as these three
  antioxidants were present, as assessed by the amounts of
  cholesterylester hydroperoxides formed during this period. Following
  consumption of these antioxidants, and in the presence of alpha-
  tocopherol, the rate of hydroperoxide formation increased sharply
  with roughly 2 molecules of cholesterylester hydroperoxides being
  formed for each peroxidation initiating event. Supplementation of
  AMVN-oxidizing plasma with exogenous bilirubin at the onset of rapid
  lipid peroxidation, i.e. after depletion of endogenous ubiquinol-10,
  ascorbate, and bilirubin, led to a halt in both hydroperoxide
  formation and consumption of alpha-tocopherol. When isolated LDL was
  incubated with AMVN, approximately 9 molecules of cholesterylester
  hydroperoxides were formed per peroxidation initiating event and
  while alpha-tocopherol was consumed. Addition of free or albumin-
  bound bilirubin to isolated LDL at the onset of oxidation resulted in
  a strong inhibition of hydroperoxide formation and alpha-tocopherol
consumption, the effect being more pronounced with the free pigment.
  Addition of the corresponding amounts of albumin alone was without
  effect. In the presence of albumin-bound bilirubin, some 30% of the
  pigment was initially converted into biliverdin, whereas formation of
  this oxidation product was not observed with the free pigment. Also,
  the presence of bilirubin oxidase partially reversed the inhibitory
  activity of bilirubin on AMVN-induced LDL oxidation in the absence
  but not presence of albumin. An attenuation of hydroperoxide
  formation and a temporary increase in LDL's alpha-tocopherol
  concentration were observed when free- or albumin-bound bilirubin
  were added to AMVN-oxidizing, alpha-tocopherol-containing LDL. In
  contrast, hydroperoxide formation was not inhibited significantly
  when the albumin-bound pigment was added to oxidizing LDL after
  complete consumption of its alpha-tocopherol. Our results show that
  bilirubin inhibits oxidation of LDL lipids initiated within the
  lipoprotein core and indicate that this activity is mediated by
  interaction of the pigment with LDL's alpha-tocopherol.

Institutional address:
     Biochemistry Group
     Heart Research Institute
     Sydney
     New South Wales
     Australia.

*****LANCET*****

(REFERENCE 13 OF 23)
91287428

Benaron DA  Bowen FW
Variation of initial serum bilirubin rise in newborn infants with
  type of illness [see comments]

In: Lancet (1991 Jul 13) 338(8759):78-81

Hyperbilirubinaemia in newborn infants is generally regarded as a
  problem, and bilirubin itself as toxic metabolic waste, but the high
  frequency in newborn infants suggests that the excess of neonatal
  bilirubin may have a positive function. To investigate the hypothesis
  that bilirubin has a role as a free-radical scavenger, the rate of
  rise in serum bilirubin in the first few days of life was measured in
  44 infants with five illnesses thought to enhance free-radical
  production and in 58 control infants. The infants were selected from
  2700 consecutive births by exclusion of those with factors known to
  affect bilirubin metabolism, including enteral feeding. The control
  infants were those who seemed to be ill and received treatment,
  including restriction of enteral feeds, but in whom no illness, or
  disorders not related to free-radical production, were found. The
  mean serum bilirubin rise was significantly lower in the combined
  illness group than in the control group (36.1 [95% Cl 26.9-45.3] vs
  66.7 [55.9-77.5] mumol.l-1.day-1; p less than 0.0001). In subgroup
  analyses the mean rises in infants with circulatory failure, neonatal
  depression/asphyxia, aspiration syndromes, and proven sepsis were
  significantly lower than in controls matched for gestational age and
  birthweight, but rises in infants with respiratory distress and their
  matched controls did not differ. These findings are consistent with
  the hypothesis that bilirubin is consumed in vivo as an antioxidant. Such
consumption may operate in vivo in addition to the standard
  pathways for bilirubin metabolism (productio   isomerisation, and
  excretion).

Lancet (1991 Jul 13) 338(8759):78-81
*********************************************
Institutional address:
     Section on Newborn Pediatrics
     Pennsylvania Hospital
     Philadelphia.

*****METHODS IN ENZYMOLOGY*****

(REFERENCE 14 OF 23)
91041806

Stocker R  McDonagh AF  Glazer AN  Ames BN
Antioxidant activities of bile pigments: biliverdin and bilirubin.

In: Methods Enzymol (1990) 186:301-9

[No Abstract Available]


*****PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE*****

(REFERENCE 15 OF 23)
92253589

Krinsky NI
Mechanism of action of biological antioxidants.

In: Proc Soc Exp Biol Med (1992 Jun) 200(2):248-54

More and more diseases have been proposed to have a radical or
  oxidant involvement. Although in most cases we do not know if this
  involvement is a cause or a result of the disease process, it is
  still valuable to learn about those compounds or enzymes that might
  block, inhibit, or prevent radical-initiated reactions. Therefore, it
  becomes increasingly important to understand which compounds can
  function as antioxidants, where they are located in the body, and
  what their mechanism of action might be. As we increase our knowledge
  in these areas, we will have a better opportunity to propose
  interventions that might suppress or even reverse some of the ravages
  of oxidant-based diseases in humans.

Institutional address:
     Department of Biochemistry
     Tufts University School of Medicine
     Boston
     Massachusetts 02111-1837.


*** <NOT IN University of Colorado Boulder> ***

*****ACTA PAEDIATRICA*****

(REFERENCE 16 OF 23)
95037113

Varsila E  Hallman M  Andersson S
Free-radical-induced lipid peroxidation during the early neonatal
  period.

In: Acta Paediatr (1994 Jul) 83(7):692-5

The effect of gestational age on postnatal free-radical-mediated
  lipid peroxidation was studied in 19 term (gestational age 37-42
  weeks) and 21 healthy preterm (gestational age 31-36 weeks) infants
  by measurement of expired ethane and pentane during the first 7 days
  of life. Ethane (11.9 versus 5.7 pmol/kg/min; p = 0.0001) and pentane
  (11.4 versus 7.5 pmol/kg/min; p = 0.01) were significantly higher in
  preterm than in term infants. Correlations were found between
  gestational age and ethane (r = 0.60, p = 0.0001) for days 1-7 and
  pentane (r = 0.54, p = 0.0003) for days 3-7; and between birth weight
  and ethane (r = 0.58, p = 0.0001) and pentane (r = 0.55, p = 0.0003).
  These results indicate that during the postnatal period, immaturity
  is a major factor determining the rate of free-radial-mediated lipid
  peroxidation.

Institutional address:
     Children's Hospital
     University of Helsinki
     Finland.

*****CLINICS IN PERINATOLOGY*****

(REFERENCE 17 OF 23)
90315758

McDonagh AF
Is bilirubin good for you?

In: Clin Perinatol (1990 Jun) 17(2):359-69

Bilirubin is generally considered to be a diagnostically useful,
  sometimes toxic, metabolic waste product--and nothing more. Many
  studies, however, summarized in this article, have shown that
  bilirubin is an effective lipid-soluble antioxidant in vitro, even at
  physiologic concentrations, vying with even vitamin E in its ability
  to intercept and inhibit free radical chain reactions that generate
  hazardous lipid peroxides. These studies suggest that bilirubin may
  have a biochemical function in vivo and belong to a group of low-
  molecular weight antioxidants that together provide protection from
  cellular damage by endogenous-organic free radicals. Dovetailing with
  the notion that bilirubin may have a protective function is the
  recent discovery that heme oxygenase, one of the enzymes responsible
  for bilirubin formation, is a heat-shock protein, one of a group of
  proteins that are thought to protect organisms from oxidative and
  other forms of biochemical stress. Thus, the biochemical path from
  red to green to yellow may defend as well as degrade, and modest
  levels of the end product may possibly be physiologically beneficial.

Institutional address:
     Department of Medicine
     University of California
     San Francisco.

*****FORTSCHRITTE DER MEDIZIN*****

(REFERENCE 18 OF 23)
94292066

Bervoets K  Schlenzig JS  Bohles H
[Bilirubin in the early neonatal period. Is there a positive aspect
  of hyperbilirubinemia?--A medical hypothesis]

Bilirubin in der fruhen Neugeborenenperiode. Gibt es positive Aspekte
  einer Hyperbilirubinamie?--Eine medizinische Hypothese.

In: Fortschr Med (1994 May 10) 112(13):192-4  (Published in German)

The fact that almost all neonates exhibit a "physiological" jaundice,
  prompts the question whether bilirubin, usually exclusively
  considered a potentially toxic endproduct of the metabolism of heme,
  might not also have a positive task in the first days of life. A
  recently discovered property of bilirubin under in vitro conditions
  is its ability to combine with free oxygen radicals such as are
  produced in the oxidative metabolic processes of the neonate
  immediately following birth. In the present article, the concept of
  the anti-oxidative effect of bilirubin, and its translation to the
  early neonatal period is presented and discussed on the basis of a
  number of examples.

Institutional address:
     Zentrum der Kinderheilkunde
     Allgemeine Padiatrie I
     Universitat Frankfurt/M.

*****FREE RADICAL RESEARCH COMMUNICATIONS*****

(REFERENCE 19 OF 23)
89253034

Stocker R  Peterhans E
Antioxidant properties of conjugated bilirubin and biliverdin:
  biologically relevant scavenging of hypochlorous acid.

In: Free Radic Res Commun (1989) 6(1):57-66

Conjugated bilirubin at low micromolar concentrations strongly
  inhibits the luminol-enhanced chemiluminescence response of
  stimulated human polymorphonuclear leukocytes. In contrast, it does
  not inhibit either reduction of ferricytochrome c or lucigenin-
  mediated chemiluminescence of stimulated cells. Also, conjugated
  bilirubin and its metabolic precursor, biliverdin, do not inhibit the
  enzyme myeloperoxidase (MPO) since (i) the MPO-dependent oxidation of
  guaiacol is not affected by biliverdin and (ii) the spectral changes
  observed when conjugated bilirubin is oxidized by a MPO-H2O2-Cl(-)-
  system are very similar to those obtained with reagent HOCl. As
  judged from these spectroscopic studies, each molecule of conjugated
  bilirubin can scavenge one molecule of HOCl giving rise to an
  oxidation product that itself is capable of scavenging further
  molecules of HOCl. Importantly, at physiological pH, both bile
  pigments can efficiently protect the elastase-inhibitory capacity of
  alpha 1-antiprotease against inactivation by reagent HOCl.

Institutional address:
     Institute of Veterinary Virology
     University of Berne
     Switzerland.


*****ITALIAN JOURNAL OF GASTROENTEROLOGY*****

(REFERENCE 20 OF 23)
92199250

Lang I  Nekam K  Deak G  Muzes G  Gonzales-Cabello R  Gergely P
  Csomos G  Feher J
Immunomodulatory and hepatoprotective effects of in vivo treatment
  with free radical scavengers.

In: Ital J Gastroenterol (1990 Oct) 22(5):283-7

The hepatoprotective and immunomodulatory effects of silymarin and
  amino-imidazol-carboxamid-phosphate were studied in 60 patients with
  compensated alcoholic cirrhosis of the liver in a one month double
  blind clinical trial. Treatment with both drugs normalized the
  elevated levels of aspartate aminotransferase, alanine
  aminotransferase and serum bilirubin, markedly reduced the high level
  of gamma-glutamyl transferase, increased lectin-induced
  lymphoblasttransformation, decreased the percentage of CD8+ cells and
  suppressed lymphocytotoxicity. None of these changes occurred in the
  placebo-treated group. Thus the hepato-protective effects of
  silymarin and amino-imidazol-carboxamid-phosphate are accompanied by
  changes in parameters of cellular immunoreactivity of the treated
  patients.

Institutional address:
     Second Department of Medicine
     Semmelweis University Medical School
     Budapest
     Hungary.

*****JOURNAL OF PERINATOLOGY*****

(REFERENCE 21 OF 23)
95054551

Hegyi T  Goldie E  Hiatt M
The protective role of bilirubin in oxygen-radical diseases of the
  preterm infant.

In: J Perinatol (1994 Jul-Aug) 14(4):296-300

We hypothesized that because bilirubin is a potent free-radical
  quencher, infants without disorders that have oxygen-radical disease
  (ORD)-mediated mechanisms may have higher bilirubin levels than
  infants suffering from conditions possibly associated with ORD-
  mediated mechanisms (e.g., necrotizing enterocolitis, broncopulmonary
  dysplasia, intraventricular hemorrhage, and retinopathy of
  prematurity). We identified 25 infants (birth weight 912 +/- 208 gm,
  gestational age 27 +/- 3 weeks) who comprised the ORD group and
  compared them with 57 controls (birth weight 1242 +/- 248 gm,
  gestational age 31 +/- 3 weeks). Infants with ORD had lower peak
  serum bilirubin concentrations, later ages at peak, and lower
  incidence of peak bilirubin concentrations exceeding 10 or 15 mg/dl.
  In addition, these infants exhibited a slower rate of bilirubin rise
  and a smaller area under the bilirubin-time curve measure compared
  with controls. To control for different birth weights, we analyzed
  subgroups weighing < 1000 gm. Significant differences were again
  identified in peak bilirubin concentrations, age at peak,
  phototherapy duration, and area under the curve. In this population
  of preterm infants, higher bilirubin levels were associated with a
  lower incidence of oxygen radical-mediated injury.
Institutional address:
     Department of Pediatrics
     UMDNJ-Robert Wood Johnson Medical School
     St. Peter's Medical Center
     New Brunswick 08903.

*****SEIKAGAKU.  JOURNAL OF JAPANESE BIOCHEMICAL SOCIETY*****

(REFERENCE 22 OF 23)
95279840

Yamaguchi T
[Bilirubin production and its physiological significance]

In: Seikagaku (1995 Feb) 67(2):148-51  (Published in Japanese)

[No Abstract Available]

Institutional address:
     Department of Biochemical Genetics
     Tokyo Medical and Dental University.


*****TANPAKUSHITSU KAKUSAN KOSO. PROTEIN, NUCLEIC ACID, ENZYME*****

(REFERENCE 23 OF 23)
89283236

Onishi S  Itoh S  Isobe K  Ochi M  Kondoh M
[Pathophysiological significance of bilirubin in neonatal jaundice as
  a defence mechanism against active oxygen during perinatal period]

In: Tanpakushitsu Kakusan Koso (1988 Dec) 33(16):3005-16
  (Published in Japanese)

[No Abstract Available]


Kate



At 07:01 AM 5/19/96 GMT, midasgold wrote:
>>some level of jaundice is desireable due to the free radical 
>>scavenging effect of bilirubin 
> 
>Kate - 
> 
>I would be very interested in the studies on this to which you referred. 
>My second baby (born in '83) had jaundice, which I now believe was
>prolonged due to my following the doctor's recommendation to give him H20
>(instead of colostrum).  I was furthermore told that this was "breastmilk
>jaundice" - even though it occurred shortly after his birth - and I should
>stop BFing for 24-48 hours...this advice I did not follow.  In addition to
>the aforementioned studies, what is the latest information that you and/or
>anyone else on Lactnet have to share on "breastmilk jaundice?" 
> 
>Deanna Goldberg, BS, AAHCC 
>Certified Childbirth Educator 
>Labor-Support Doula 
>West Hempstead, NY
>
>
Kate

In the United States, breastfeeding legislation has been enacted in ten
states over the past two years, and many more states have pending bills. The
legislation typically clarifies the fact that breastfeeding is not indecent
exposure, and thus not criminal behavior. Most of the states have gone
further than this, making it perfectly clear that a woman has a right to
breastfeed any place she has the right to be. --
http://www.prairienet.org/llli/LawBills.html

http://www.cs.colorado.edu/~kolina/Home.html (my home page)
http://www.cs.colorado.edu/~grunwald/House.html   Buy our House!

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