Configurational isomerization of bilirubin and the mechanism of jaundice phototherapy

Lightner, David A.; Wooldridge, Timothy A.; McDonagh, Antony F.

doi:10.1016/0006-291x(79)90857-x

Cited by 80 publications

(44 citation statements)

References 15 publications

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“…The properties of these photobilirubins suggested that they were bilirubin isomers, and that they corresponded to the major bilirubin derivatives formed during phototherapy of jaundice in vitro. Possibly related in vitro photoproducts have been reported by Lightner et al (12)(13)(14), though direct comparisons are not possible since they were unable to isolate and purify their derivatives (16). This paper supports the role of the photobilirubins in the catabolism of bilirubin during phototherapy of the Gunn rat by showing that they are excreted rapidly in bile when given intravenously to the Gunn rat, and by showing that they appear endogenously in bile collected during phototherapy of these jaundiced animals.…”

Section: Introductionsupporting

confidence: 63%

Excretion of administered and endogenous photobilirubins in the bile of the jaundice gunn rat.

Stoll¹,

Zenone²,

Ostrow³

1981

J. Clin. Invest.

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A B S T R A C T Radiolabeled photobilirubins, prepared in vitro by anaerobic illumination of [14C]bilirubin, were injected intravenously into homozygous jaundiced Gunn rats with an external bile fistula. With the animals kept in darkness, the labeled photobilirubins were excreted rapidly in bile. Photobilirubins IA and IB were excreted primarily as unconjugated bilirubin, whereas photobilirubin II was excreted primarily as photobilirubin II and not converted into bilirubin. Bile of Gunn rats given no exogenous pigments, but undergoing phototherapy, contained a large proportion of photobilirubin II and, ifcollected in liquid nitrogen, traces of photobilirubins I; neither was found in bile when these rats were kept in the dark. Because there is prior evidence that these photobilirubins are isomers of bilirubin, these experiments indicate that the major mechanism of phototherapy is photoisomerization of bilirubin. Photobilirubin II. is the unidentified major photoderivative described previously, whereas formation of photobilirubins IA and IB, and their reversion to bilirubin-IXa, account for the remarkably increased output of the parent pigment during phototherapy.

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Section: Introductionsupporting

confidence: 63%

Excretion of administered and endogenous photobilirubins in the bile of the jaundice gunn rat.

Stoll¹,

Zenone²,

Ostrow³

1981

J. Clin. Invest.

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“…4Z,15 Z-Bilirubin-IX a, obtained from Sigma Chemical Company, was purified by washing a chloroform solution of it with aqueous NaHCO, according to Lightner et al [6]. Defatted human serum albumin was prepared from fresh blood plasma as described previously [7].…”

Section: Methodsmentioning

confidence: 99%

Binding of Photobilkirubin to Human Serum Albumin

Lamola¹,

Flores²,

Blumberg³

1983

European Journal of Biochemistry

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Results of experiments based upon circular dichroic spectra suggest that configurationally (Z -+ E ) isomerized bilirubin (photobilirubin) binds to human serum albumin at the primary bilirubin binding site with an affinity only 2-3-times lower than that of bilirubin. The high affinity of photobilirubin for albumin, comparable to that of bilirubin, supports the roles of albumin in the stabilization and transport of the isomerized pigment in vivo and strongly suggests that albumin also functions to sequester photobilirubin effectively, reducing its toxic potential. The high affinity of photobilirubin for albumin predicts that the isomerized pigment, formed in large amounts during phototherapy for neonatal hyperbilirubinemia, should not appear in the fast-diazo-reacting ('direct') bilirubin pool nor should it interfere with nonspectroscopic bilirubin binding tests. These predictions were confirmed for the Evelyn and Malloy diazo assay for 'direct' bilirubin and a Sephadex chromatography method for assessing 'loosely bound' plasma bilirubin.

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“…It clearly appears from Figures 2 and 3 that the photopigment formed in our experiments can be partitioned from chloroform into water at pH as low as 7.2-7.4. On the other hand, previous reports indicate that photobilirubin can be extracted by pH 8.5-9.0 tris buffer, but not by 0.1 M phosphate buffer at pH 7.4 (10). The discrepancy in solvent partitioning of the bilirubin photoderivatives between us and other authors (10) could be explained taking into account the higher efficacy of the our continuous extraction, or assuming that, in addition to E-isomers, significant amounts of other photoproducts are formed that are soluble even in water with pH at near neutral values.…”

Section: Methodsmentioning

confidence: 69%

“…Their formation precedes or accompanies other photoreactions of bilirubin, such as photo-oxidation (8), photo-addition of nucleophilic molecules to the 18-vinyl group (4,12,13), photoscrambling to IIIa and XIIa isomers (I), and production of certain poorly characterized yellow products, e.g., photobilirubin I1 (27), "430 pigment" (6), "41 5 pigment" (21), and "peak 1" (5). The configurational photoisomers of bilirubin, commonly known as photobilirubin (9), appear to be more polar, less lipophilic, and probably more acidic than the natural pigment (10). These properties are a consequence of the reduction in the number of intramolecular hydrogen bonds involving the carboxy groups of bilirubin (14) (Fig.…”

mentioning

confidence: 99%

pH Dependence of the Water Solubility of Bilirubin Photo-Derivatives and its Relevance to Phototherapy

1984

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Configurational isomerization of bilirubin and the mechanism of jaundice phototherapy

Cited by 80 publications

References 15 publications

Excretion of administered and endogenous photobilirubins in the bile of the jaundice gunn rat.

Excretion of administered and endogenous photobilirubins in the bile of the jaundice gunn rat.

Binding of Photobilkirubin to Human Serum Albumin

pH Dependence of the Water Solubility of Bilirubin Photo-Derivatives and its Relevance to Phototherapy

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