Pro‐ und Antioxydantien auf dem Fettgebiet II: Über natürlich vorkommende Antioxydantien, 1. Mitteilung

Kaufmann, Christoph; Garloff, H.

doi:10.1002/lipi.19610630406

Cited by 23 publications

(3 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bilirubin is often regarded as cytotoxic because it is associated with neonatal jaundice, and it may cause brain damage at high concentrations. However, such damaging effects are unusual 1a and BR has beneficial effects due to its antioxidant properties which were recognized some 50 years ago . The bile pigments are of particular significance as antioxidants because they provide a continuous natural source of protection against free-radical oxidation in human blood .…”

Section: Introductionmentioning

confidence: 99%

Polypyrroles as Antioxidants: Kinetic Studies on Reactions of Bilirubin and Biliverdin Dimethyl Esters and Synthetic Model Compounds with Peroxyl Radicals in Solution. Chemical Calculations on Selected Typical Structures

et al. 2005

View full text Add to dashboard Cite

[reaction: see text] Rate constants for hydrogen-atom transfer (HAT) from bilirubin dimethyl ester (BRDE) and biliverdin dimethyl ester (BVDE) to peroxyl radicals during inhibited autoxidation of styrene initiated by azo-bisisobutyronitrile (AIBN) were k(inh)(BRDE) = 22.5 x 10(4) and k(inh)(BVDE) = 10.2 x 10(4) M(-1) s(-1), and the stoichiometric factors (n) were 2.0 and 2.7, respectively. A synthetic tetrapyrrole (bis(dipyrromethene)) containing the alpha-central (2,2') CH2 linkage gave k(inh) = 39.9 x 10(4) M(-1) s(-1) and n = 2.3, whereas the beta-linked (3,3') isomer was not an active antioxidant. Several dipyrrinones were synthesized as mimics of the two outer heterocyclic rings of bilirubin and biliverdin. The dipyrrinones containing N-H groups in each ring were active antioxidants, whereas those lacking two such "free" N-H groups, such as N-CH3 dipyrrinones and dipyrromethenes, did not exhibit antioxidant activity. Overall, the relative k(inh) values compared to those of phenolic antioxidants, 2,6-di-tert-butyl-4-methoxyphenol (DBHA) and 2,6-di-tert-butyl-4-methylphenol (BHT), were 2,2'-bis(dipyrromethene) > BRDE > DBHA > dipyrrinones > BVDE > BHT. This general trend in antioxidant activities was also observed for the inhibited autoxidation of cumene initiated by AIBN. Chemical calculations of the N-H bond dissociation enthalpies (BDEs) of the typical structures support a HAT mechanism from N-H groups to trap peroxyl radicals. Intramolecular hydrogen bonding of intermediate nitrogen radicals has a major influence on the antioxidant activities of all compounds studied. Indeed, chemical calculations showed that the initial nitrogen radical from a dipyrrinone is stabilized by 9.0 kcal/mol because of H-bonding between the N-H remaining on one ring and the ground-state pyrrolyl radical of the adjacent ring in the natural zusammen structure. The calculated minimum structure of bilirubin shows strong intramolecular H-bonding of the N-H groups with carbonyl groups resulting in the known "ridge-tile" structure which is not an active HAT antioxidant. The calculated minimum structure of biliverdin is planar. BRDE is readily converted into BVDE by reaction with the electron-deficient DPPH* radical under argon in chlorobenzene. An electron-transfer mechanism is proposed for the initiating step in this reaction, and this is supported by the relatively low ionizing potential of a model dipyrrole representing the two central rings of bilirubin.

show abstract

Section: Introductionmentioning

confidence: 99%

Polypyrroles as Antioxidants: Kinetic Studies on Reactions of Bilirubin and Biliverdin Dimethyl Esters and Synthetic Model Compounds with Peroxyl Radicals in Solution. Chemical Calculations on Selected Typical Structures

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Abnormally high plasma concentrations are associated with the risk of developing neurologic dysfunction due to preferential deposition of bilirubin in brain and its toxic effects on cell functions. In fact for many years, biliverdin and bilirubin were generally regarded as waste products of heme metabolism in higher animals, although earlier work suggested that these bile pigments might play a role as natural antioxidants, since small quantities of the pigment stabilize vitamin A and ␤-carotene during intestinal uptake, and animals with low plasma bilirubin showed early signs of vitamin E deficiency (4,5).…”

mentioning

confidence: 99%

Limited Role for the Bilirubin-Biliverdin Redox Amplification Cycle in the Cellular Antioxidant Protection by Biliverdin Reductase

Maghzal

Leck

Collinson

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

In mammalian cells, heme is degraded by heme oxygenase to biliverdin, which is then reduced to bilirubin by biliverdin reductase (BVR). Both bile pigments have reducing properties, and bilirubin is now generally considered to be a potent antioxidant, yet it remains unclear how it protects cells against oxidative damage. A presently popular explanation for the antioxidant function of bilirubin is a redox cycle in which bilirubin is oxidized to biliverdin and then recycled by BVR. Here, we reexamined this putative BVR-mediated redox cycle. We observed that lipid peroxidation-mediated oxidation of bilirubin in chloroform, a model of cell membrane-bound bilirubin, did not yield biliverdin, a prerequisite for the putative redox cycle. Similarly, H 2 O 2 did not oxidize albumin-bound bilirubin to biliverdin, and in vitro oxidation of albumin or ligandin-bound bilirubin by peroxyl radicals gave modest yields of biliverdin. In addition, decreasing cellular BVR protein and activity in HeLa cells using RNA interference did not alter H 2 O 2 -mediated cell death, just as BVR overexpression failed to enhance protection of these cells against H 2 O 2 -mediated damage, irrespective of whether bilirubin or biliverdin were added to the cells as substrate for the putative redox cycle. Similarly, transformation of human BVR into hmx1 (heme oxygenase) mutant yeast did not provide protection against H 2 O 2 toxicity above that seen in hmx1 mutant yeast expressing human heme oxygenase-1. Together, these results argue against the BVR-mediated redox cycle playing a general or important role as cellular antioxidant defense mechanism.

show abstract

“…Some earlier and neglected work has also suggested that bilirubin might play a role as an antioxidant (9)(10)(11). Indeed, reactions of bilirubin involving free radicals (12,13) or toxic oxygen reduction products are well documented in the literature: unconjugated bilirubin scavenges singlet oxygen with high efficiency (14), reacts with superoxide anion (15) and peroxyl radicals (7), and serves as a reducing substrate for peroxidases in the presence of hydrogen peroxide or organic hydroperoxides (16,17).…”

mentioning

confidence: 99%

Potential role of conjugated bilirubin and copper in the metabolism of lipid peroxides in bile.

Stocker

Ames

1987

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

125

View full text Add to dashboard Cite

Conjugated bilirubin and copper ions at their physiological concentrations in bile may play an important role in hydroperoxide and other detoxification. Conjugated bilirubin may also be an important chain-breaking antioxidant preventing lipid peroxidation. Bilirubin ditaurine (BR-DT), a water-soluble model compound of conjugated bilirubin, completely prevents the peroxyl radical-induced oxidation of phosphatidylcholine in either multilamellar liposomes or micelles. This antioxidant activity is associated with the bilirubin moiety of BR-DT, since taurine alone is inefficient in scavenging peroxyl radicals. The number of peroxyl radicals trapped per molecule of BR-DT is 1.9, compared to 4.7 trapped per molecule of biliverdin, the water-soluble physiological precursor of bilirubin. Peroxyl radical-induced oxidation of BR-DT results in a spectral shift in maximal absorbance toward shorter wavelengths; biliverdin is not formed as a major oxidation product. BR-DT, but neither taurine nor biliverdin, greatly accelerates the cupric ion-catalyzed decomposition of linoleic acid hydroperoxide. In the presence of ferric ion, BR-DT shows no lipid hydroperoxide-degrading activity. Addition of cupric ion to BR-DT results in formation of a complex with spectral features similar to that of a biliverdin-cupric ion complex, indicating that BR-DT and cupric ion undergo redox reactions.

show abstract

Pro‐ und Antioxydantien auf dem Fettgebiet II: Über natürlich vorkommende Antioxydantien, 1. Mitteilung

Cited by 23 publications

References 59 publications

Polypyrroles as Antioxidants: Kinetic Studies on Reactions of Bilirubin and Biliverdin Dimethyl Esters and Synthetic Model Compounds with Peroxyl Radicals in Solution. Chemical Calculations on Selected Typical Structures

Polypyrroles as Antioxidants: Kinetic Studies on Reactions of Bilirubin and Biliverdin Dimethyl Esters and Synthetic Model Compounds with Peroxyl Radicals in Solution. Chemical Calculations on Selected Typical Structures

Limited Role for the Bilirubin-Biliverdin Redox Amplification Cycle in the Cellular Antioxidant Protection by Biliverdin Reductase

Potential role of conjugated bilirubin and copper in the metabolism of lipid peroxides in bile.

Contact Info

Product

Resources

About