Phototherapy for neonatal jaundice. Stereospecific and regioselective photoisomerization of bilirubin bound to human serum albumin and NMR characterization of intramolecularly cyclized photoproducts

McDonagh, Antony F.; Palma, Lucita A.; Lightner, David A.

doi:10.1021/ja00388a104

Cited by 126 publications

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“…The second fastest photoehemical reaction of bilirubin is structural isomerization to lumirubin (6). During phototherapy the serum concentration of lumirubin is lower than the concentration of the configurational isomers: 2 to 6 versus 15 to 20% of the total serum bilirubin.…”

Section: Discussionmentioning

confidence: 99%

“…However, serial sampling at 15-20 min intervals for 180 min from 14 individual fetuses (91-139 days) showed that TSH was secreted in a markedly exaggerated pulsatile manner compared to that observed after birth. The mean amplitude of TSH pulses fell (p < 0.005) from 5.9 2 8.1 pU/ml in the fetuses to 2.1 + 1.1 pU/ml in five neonatal lambs (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) days) and to 1.5 f 0.4 pU/ml in three adult nonpregnant ewes. The mean pulse frequency for the 14 fetuses was 0.7 + 0.3 pulses/h and was reduced (p < 0.001) to 0.3 + 0.1 pulseslh in lambs and to 0.3 f 0.1 pulses/h in the ewes.…”

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confidence: 94%

“…All of these reactions yield photoproducts which are more polar and therefore presumably more easily excreted than native bilirubin. The fastest photochemical reaction is a Z to E isomerization reaction (5,8) which in human infants yields primarily the 4Z,15E-bilirubin isomer (6). This reaction is readily reversible and up to 20% of the total bilirubin can be converted to this isomer during phototherapy (9)(10)(11)(12).…”

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Phototherapy for Neonatal Jaundice: in Vivo Clearance of Bilirubin Photoproducts

et al. 1985

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ABSTRACT. Phototherapy results in the conversion of native bilirubin to more water-soluble configurational and structural isomers. The serum half-life for the configurational isomer, the principal photoproduct in vivo, was determined by high pressure liquid chromatography in six premature infants following cessation of phototherapy. The mean half-life for this isomer was 15 h. The excretion of this isomer, calculated from the measured half-life, is less than half of daily bilirubin production, and therefore cannot account for the total bilirubin elimination observed during phototherapy. The serum concentration of the structural isomer, lumirubin, is lower than that of the configurational isomer; however, excretion is more rapid (serum half-life < 2 h). Because of its rapid excretion, lumirubin may be an important pathway for bilirubin elimination during phototherapy. (Pediatr Res 19: 205-208, 1985) Abbreviation HPLC, high pressure liquid chromatography Despite the widespread use of phototherapy in the treatment of neonatal hyperbilirubinemia (l), the detailed mechanism by which visible light affects bilirubin metabolism in jaundiced newborns is not known. The purpose of this study was to measure the rate of elimination of the principal bilirubin photoproduct, 4Z,15E-bilirubin, and to determine whether this is sufficient to Received June 22, 1984; accepted October 3, 1984. Address account for the decline in plasma bilirubin observed during phototherapy.Bilirubin, derived from the degradation of heme, is a potentially toxic, highly lipophylic molecule. In mammals this pigment is ravidlv cleared from the circulation and excreted as a ducuronide~onju~ate, primarily in the bile (2). Newborn i n f a k commonly develop hyperbilirubinemia due in part to a decreased ability to conjugate bilirubin and an increased pigment load. During vhototheravy, the most commonlv used treatment for unconj~~ated&~~dilirubinemia, bilirubin undergoes several reactions (3-7). All of these reactions yield photoproducts which are more polar and therefore presumably more easily excreted than native bilirubin. The fastest photochemical reaction is a Z to E isomerization reaction (5, 8) which in human infants yields primarily the 4Z,15E-bilirubin isomer (6). This reaction is readily reversible and up to 20% of the total bilirubin can be converted to this isomer during phototherapy (9-12).Since the quantum yield of the configurational isomerization reaction is at least 40 times greater than that for any other photochemical reaction of bilirubin (8), it has been assumed that the elimination of bilirubin during phototherapy is the result of formation and excretion of this photoproduct. We have used a rapid, quantitative HPLC method (5) to measure the half-life of the configurational isomer in serum of preterm infants undergoing phototherapy. We have found that the rate of elimination of the 4Z,15E-bilirubin isomer is much slower than previously reported (13) and cannot account for the decline in serum bilirubin observed in infants treated wit...

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Phototherapy for Neonatal Jaundice: in Vivo Clearance of Bilirubin Photoproducts

et al. 1985

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“…Photooxidation may also occur (5,6). Due to increased polarity, these isomers can be excreted in bile and urine, bypassing the need for conjugation.…”

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Early formation of bilirubin isomers during phototherapy for neonatal jaundice: effects of single vs. double fluorescent lamps vs. photodiodes

et al. 2015

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Background:In neonatal jaundice, phototherapy converts bilirubin to more polar photoisomers which can be excreted without conjugation. We measured changes in the concentration of bilirubin Z,E-photoisomer during the first 4 h of intensive phototherapy using single fluorescent lights as a reference, compared to double fluorescent lights, and a single unit of photodiodes. Methods: Neonates (N = 42; birth weight: 1,200-4,690 g; gestational age: 28-42 wk) were studied during phototherapy. Infants were randomized to: (i) single, or (ii) double fluorescent phototherapy; or (iii) single unit photodiodes. Irradiance was measured. Serum bilirubin (by cooximetry) and Z,E bilirubin (by high-pressure liquid chromatography) were measured at 0,15, 30, 60, 120, and 240 min after the start of phototherapy. Data were analyzed with a linear mixed model. results: There was a highly significant increase of Z,E-bilirubin over time (P < 0.0001), starting at 15 min. Photoisomers reached ~25% of total bilirubin concentration after 4 h. However, there were no significant differences between the three randomized groups in spite of significantly higher irradiance using double fluorescent lights vs. single fluorescent or photodiodes. conclusion: Formation of bilirubin photoisomers is rapid, and occurs early during intensive phototherapy for neonatal jaundice. The rate and level of photoisomerization was not influenced by irradiance and light source. P hototherapy is the standard treatment for hyperbilirubinemia in newborns, and is administered to prevent kernicterus and other sequelae of bilirubin neurotoxicity (1).It is effective and considered safe. However, a recent report suggests that "aggressive" phototherapy in the smallest infants of birth weight 501-750 g may be associated with increased risk of death (2).When native bilirubin IXα (Z,Z) in neonates is exposed to light, a rapid photochemical reaction produces water-soluble configurational (4Z,15E; 4E,15Z; 4E,15E) and structural (Z-lumirubin; E-lumirubin) isomers (3,4). Photooxidation may also occur (5,6). Due to increased polarity, these isomers can be excreted in bile and urine, bypassing the need for conjugation. It has recently been suggested that these isomers, because of their polarity, should be less able to cross the bloodbrain barrier (1,7). If this is correct, photoisomer formation might be directly neuroprotective, irrespective of the effect on excretion. Experimental data suggest that bilirubin photoisomers are less toxic than the native IX α (Z,Z), but there are methodological weaknesses in these studies (1). Thus, experimental proof of the hypothesized direct neuroprotective effects of photoisomerization is still needed. Both different light qualities and variable light irradiance are commonly employed in practical phototherapy. Herein we have investigated whether such factors may impact on photoisomer formation.The common light sources used in phototherapy are either fluorescent, or tungsten-halogen lamps with wide emission spectrum, or light-emitting diodes (LEDs) wi...

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“…Other bilirubin isomers, including bilirubin-III α and bilirubin-XIII α, were eliminated because their 1 H NMR spectra are substantially different (McDonagh et al, 1982).…”

Section: Proposed Researchmentioning

confidence: 99%

Bilirubin: an Animal Pigment in the Zingiberales and Diverse Angiosperm Orders

Pirone¹

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Phototherapy for neonatal jaundice. Stereospecific and regioselective photoisomerization of bilirubin bound to human serum albumin and NMR characterization of intramolecularly cyclized photoproducts

Abstract: Anders als bei der Bindung von (Z,Z)‐ Bilirubin IXa an tierischen Serum‐Albumin (SA) weist die an menschliches SA gebundene Titelverbindung bei ihrer Photoisomerisierung nur eines der beiden möglichen Diastereomeren auf.

Cited by 126 publications

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Phototherapy for Neonatal Jaundice: in Vivo Clearance of Bilirubin Photoproducts

Phototherapy for Neonatal Jaundice: in Vivo Clearance of Bilirubin Photoproducts

Early formation of bilirubin isomers during phototherapy for neonatal jaundice: effects of single vs. double fluorescent lamps vs. photodiodes

Bilirubin: an Animal Pigment in the Zingiberales and Diverse Angiosperm Orders

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