Rapid clearance of a structural isomer of bilirubin during phototherapy.

Ennever, John F.; Costarino, Andrew T.; Polin, Richard A.; Speck, William T.

doi:10.1172/jci113006

Cited by 65 publications

(45 citation statements)

References 24 publications

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“…The more important effect would be enhanced biliary and bowel function. 17,18 Oral supplementation of feeds that accompanied and followed the initial IV supplementation possibly helped decrease enterophepatic circulation and reabsorption of bilirubin from the gut.…”

Section: Discussionmentioning

confidence: 99%

Fluid supplementation in term neonates with severe hyperbilirubinemia: a randomized controlled trial study

Bandyopadhyay

Maiti

2017

Int J Contemp Pediatr

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Background: Severe neonatal jaundice can cause fatality and serious permanent effect, called kernicterus, in which the brain stem nuclei and basal ganglia are damaged. We are encouraged to work on efficacy of fluid supplementation in addition to photo therapy as a measure to reduce bilirubin level more efficiently.Methods: A randomized control trial study was conducted in Department of Paediatric Medicine, Neonatal Unit, R.G. Kar Medical College & Hospital, Kolkata, from April 2011 to March 2012. A total 100 term neonates presenting with severe non-hemolytic hyperbilirubinemia (>18 mg/dl to <25 mg/dl) were enrolled as study population. The study subjects were divided into two equal groups, study group and control group by randomization. The study group was given IV fluid supplementation in addition to photo therapy. Total serum bilirubin (TSB) level assessed periodically and results compared with control group.Results: The study results reveal a statistically significant association between the percent fall in TSB at 12 (Chi2= 7.18, p=0.000) and 24 hours (Chi2=10.69, p=0.000) in the intervention arm compared to the control group.Conclusions: Fluid supplementation along with double surface phototherapy in term neonates presenting with severe hyperbilirubinemia decreases the rate of exchange transfusion and duration of phototherapy.

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Section: Discussionmentioning

confidence: 99%

Fluid supplementation in term neonates with severe hyperbilirubinemia: a randomized controlled trial study

Bandyopadhyay

Maiti

2017

Int J Contemp Pediatr

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“…A striking example is in phototherapy of neonatal jaundice (Maisels and McDonagh, 2008), where photochemically induced isomerization and disruption of the hydrogen bonding in bilirubin facilitates excretion of the pigment in bile in unconjugated form (Lightner and McDonagh, 1984). The same general process occurs in jaundiced rats (Gunn rats) on exposure to light, but, because of differences in protein binding, the excretion kinetics of the photoisomers are different in rats and humans (Lightner and McDonagh, 1984;Ennever et al, 1985Ennever et al, , 1987.…”

Section: Compoundmentioning

confidence: 99%

Slipping Past UGT1A1 and Multidrug Resistance-Associated Protein 2 in the Liver: Effects of Steric Compression and Hydrogen Bonding on the Hepatobiliary Elimination of Synthetic Bilirubins

McDonagh

Boiadjiev²,

Lightner³

2008

Drug Metab Dispos

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ABSTRACT:The hepatobiliary metabolism and excretion of three isomeric bilirubin analogs with propanoic replaced by benzoic acid side-chains were studied in the rat. Despite their isomeric relationship and similar constitutions, the three analogs were metabolized quite differently from each other and from bilirubin. In the di-o-benzoic compound, steric hindrance involving the phenyl groups reinforces intramolecular hydrogen bonding of the two carboxyl groups. This compound is considerably less polar than bilirubin on reversephase high-performance liquid chromatography and, like bilirubin, was not excreted in bile in UGT1-deficient (Gunn) rats. But, quite unlike bilirubin, it was not glucuronidated or excreted in bile in normal rats. In contrast to both bilirubin and the di-o-benzoic isomer, the more polar m-and p-isomers, in which intramolecular hydrogen bonding of carboxyl groups is sterically difficult, were excreted rapidly in bile in unchanged form in both normal and Gunn rats. However, only one of them, the di-m-isomer, was excreted rapidly and unchanged in bile in rats (TR ؊ rats) congenitally deficient in the canalicular ATP-binding cassette transporter Mrp2. The marked differences in hepatobiliary metabolism of the three isomers studied can be rationalized on the basis of their computed three-dimensional structures and minimum-energy conformations and the remote effects of steric compression on intramolecular hydrogen bonding.Bilirubin (1) (Fig. 1) is formed in mammals by reduction of biliverdin (2), end product of most heme catabolism. It is insoluble in water, lipophilic, extensively protein-bound in plasma, and, unlike biliverdin, requires phase-2 metabolism, mainly to mono-and diglucuronides, for elimination. Once used as a liver function test (Harrop and Barron, 1931;Kornberg, 1942), bilirubin is a constituent of several Asian traditional medicines (McDonagh, 1990), and its antioxidant/anti-inflammatory properties are currently attracting attention (Stocker et al., 1987;Stocker, 2004; Ollinger et al., 2007a,b). Historically, bilirubins have been useful for investigating mechanisms of acyl glucuronidation, membrane transport, and hepatobiliary excretion. Bilirubin and its two monoglucuronides are isozyme-specific substrates for the glucuronosyl transferase UGT1A1 (Owens et al., 2005), and its three acyl glucuronides are classic examples of compounds that depend wholly on the ATP-binding cassette transporter MRP2 (ABCC2) for elimination in bile (Nies and Keppler, 2007). Deficiencies of UGT1A1 cause neonatal jaundice, Gilbert's and CriglerNajjar syndromes (Kaplan and Hammerman, 2005), and congenital deficiency of MRP2 underlies the rare Dubin-Johnson syndrome (Nies and Keppler, 2007). Studies on bilirubin glucuronides led to the discovery that acyl glucuronides of many drugs are reactive, potentially toxic, metabolites (Smith et al., 1986), and studies on bilirubin analogs have revealed how subtle changes in molecular conformation can profoundly influence hepatic metabolism (McDonagh and Lightner, 1991;...

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“…The formation of this structural isomer is currently considered the main mechanism behind the phototherapy action on the decrease in serum bilirubin levels. 2 Unlike the geometric isomer, the formation of lumirubin is influenced by the intensity of the light (irradiance) emitted by the phototherapy, increasing proportionally to the increase in irradiance. 3 It may also be speculated that newborns treated with Super LED phototherapy produced larger quantities of structural photoisomers and consequently exhibited a greater decrease in serum bilirubin levels.…”

Section: Referencesmentioning

confidence: 99%

Avaliação da eficácia clínica de uma nova modalidade de fototerapia utilizando diodos emissores de luz

Facchini¹

2007

J. Pediatr. (Rio J.)

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which two types of phototherapy using different light sources were evaluated. We believe that this is the first published Brazilian study testing equipment in which LEDs were used that employ LEDs. We really like the detailed description of the radiation monitor, information on its wavelength range and on the spectrum of the light sources used. We consider that mention of these data and standardization of the measurements are essential for understanding and evaluating results in phototherapy. We would like to address some comments we consider pertinent to the discussion.In the results, the authors refer to the mean irradiance expressing values in µW/cm 2 /nm. We believe that they probably refer to the mean of irradiance measurements at the point of peak intensity. Spectral irradiance is quantified 2 as µW/cm 2 /nm whereas irradiance values are expressed in Watts/m 2 . Mean irradiance may more suitably designate the weighted assessment of irradiance at the surface area exposed to light. If weighted irradiance were measured at the area illuminated, a considerable difference would be observed in the irradiance emitted by the two phototherapy devices, since the center to periphery decrease in spectral irradiance of the halogen phototherapy unit is significantly greater than that of the device equipped with LEDs. 3-5Another aspect regarding the results refers to the authors' report on the patients on Super LED phototherapy, who relapsed with elevated total bilirubin when withdrawn from treatment and needed to go back on phototherapy. To avoid controversy over efficacy of this type of treatment, the authors could have elaborated this in their discussion. This phototherapy system actually has a greater capacity of rapidly reduce bilirubinemia, which caused the withdrawal levels (not informed on the study) to occur before the patient had had a better glucuronidation capacity so he could have been able to suppress new increases..Finally, we believe that the wider emission spectrum of the halogen lamp, unlike the explanation provided on the study, did not interfere in the results of the phototherapy. Of the light spectrum of 380 nm to 600 nm, only the range between 400and 500 nm will be absorbed by bilirubin, thus determining its conversion into an isomer and a product of photooxidation. The decrease in values is actually attributed to the difference in the intensity rather than in the quality of irradiance.We appreciate the authors' article and we do hope that we have contributed toward a better understanding of the data reported. References

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Rapid clearance of a structural isomer of bilirubin during phototherapy.

Cited by 65 publications

References 24 publications

Fluid supplementation in term neonates with severe hyperbilirubinemia: a randomized controlled trial study

Fluid supplementation in term neonates with severe hyperbilirubinemia: a randomized controlled trial study

Slipping Past UGT1A1 and Multidrug Resistance-Associated Protein 2 in the Liver: Effects of Steric Compression and Hydrogen Bonding on the Hepatobiliary Elimination of Synthetic Bilirubins

Avaliação da eficácia clínica de uma nova modalidade de fototerapia utilizando diodos emissores de luz

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