Noninvasive monitoring of bilirubin photoisomer excretion during phototherapy
Abstract Lumirubin is the most prevalently excreted hydrophilic bilirubin photoisomer in phototherapy for neonatal jaundice caused by excess hydrophobic unconjugated bilirubin (ZZ-bilirubin). We developed a simple method to estimate the amount of lumirubin by monitoring the reverse photoisomerizatio...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-16180-9 |
| _version_ | 1818198674797232128 |
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| author | Yumiko Uchida Yukihiro Takahashi Yukihiro Morimoto Peter Greimel Asako Tosaki Akiko Kumagai Toshiya Nishikubo Atsushi Miyawaki |
| author_facet | Yumiko Uchida Yukihiro Takahashi Yukihiro Morimoto Peter Greimel Asako Tosaki Akiko Kumagai Toshiya Nishikubo Atsushi Miyawaki |
| author_sort | Yumiko Uchida |
| collection | DOAJ |
| description | Abstract Lumirubin is the most prevalently excreted hydrophilic bilirubin photoisomer in phototherapy for neonatal jaundice caused by excess hydrophobic unconjugated bilirubin (ZZ-bilirubin). We developed a simple method to estimate the amount of lumirubin by monitoring the reverse photoisomerization of lumirubin to ZZ-bilirubin. Although lumirubin formation was long considered irreversible, exposure to blue light in the presence of the fluorescent protein UnaG, which binds specifically and tightly to ZZ-bilirubin, enables the reverse photoisomerization of lumirubin. This reaction was first detected using a fluorescence assay of neonatal urine sampled during phototherapy and purified lumirubin. The phenomenon of reverse photoisomerization of lumirubin was validated using liquid chromatography–mass spectrometry, which confirmed that lumirubin is reconverted to ZZ-bilirubin in the presence of UnaG. Analyses of 20 urine samples from 17 neonates revealed a significant correlation (correlation coefficient [r] = 0.978; 95% confidence interval 0.867–0.979; P < .001) between lumirubin and ZZ-bilirubin concentration before and after reverse photoisomerization. In general, the rate of photo-reconversion of lumirubin to ZZ-bilirubin is approximately 40%. In conclusion, we demonstrate here that lumirubin can be photo-reconverted to ZZ-bilirubin via exposure to blue light in the presence of UnaG. Utilizing this approach, urinary lumirubin levels can be estimated using an easy-to-perform fluorescence assay. |
| first_indexed | 2024-12-12T02:09:38Z |
| format | Article |
| id | doaj.art-7138e2d6069a45848503ae995c4fefbb |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-12T02:09:38Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7138e2d6069a45848503ae995c4fefbb2022-12-22T00:41:56ZengNature PortfolioScientific Reports2045-23222022-07-011211910.1038/s41598-022-16180-9Noninvasive monitoring of bilirubin photoisomer excretion during phototherapyYumiko Uchida0Yukihiro Takahashi1Yukihiro Morimoto2Peter Greimel3Asako Tosaki4Akiko Kumagai5Toshiya Nishikubo6Atsushi Miyawaki7Division of Neonatal Intensive Care, Maternal, Fetal and Neonatal Medical Center, Nara Medical University HospitalDivision of Neonatal Intensive Care, Maternal, Fetal and Neonatal Medical Center, Nara Medical University HospitalR&D Division, Ushio Inc.Cell Function Dynamics, Brain Science Institute, RIKENCell Function Dynamics, Brain Science Institute, RIKENCell Function Dynamics, Brain Science Institute, RIKENDivision of Neonatal Intensive Care, Maternal, Fetal and Neonatal Medical Center, Nara Medical University HospitalCell Function Dynamics, Brain Science Institute, RIKENAbstract Lumirubin is the most prevalently excreted hydrophilic bilirubin photoisomer in phototherapy for neonatal jaundice caused by excess hydrophobic unconjugated bilirubin (ZZ-bilirubin). We developed a simple method to estimate the amount of lumirubin by monitoring the reverse photoisomerization of lumirubin to ZZ-bilirubin. Although lumirubin formation was long considered irreversible, exposure to blue light in the presence of the fluorescent protein UnaG, which binds specifically and tightly to ZZ-bilirubin, enables the reverse photoisomerization of lumirubin. This reaction was first detected using a fluorescence assay of neonatal urine sampled during phototherapy and purified lumirubin. The phenomenon of reverse photoisomerization of lumirubin was validated using liquid chromatography–mass spectrometry, which confirmed that lumirubin is reconverted to ZZ-bilirubin in the presence of UnaG. Analyses of 20 urine samples from 17 neonates revealed a significant correlation (correlation coefficient [r] = 0.978; 95% confidence interval 0.867–0.979; P < .001) between lumirubin and ZZ-bilirubin concentration before and after reverse photoisomerization. In general, the rate of photo-reconversion of lumirubin to ZZ-bilirubin is approximately 40%. In conclusion, we demonstrate here that lumirubin can be photo-reconverted to ZZ-bilirubin via exposure to blue light in the presence of UnaG. Utilizing this approach, urinary lumirubin levels can be estimated using an easy-to-perform fluorescence assay.https://doi.org/10.1038/s41598-022-16180-9 |
| spellingShingle | Yumiko Uchida Yukihiro Takahashi Yukihiro Morimoto Peter Greimel Asako Tosaki Akiko Kumagai Toshiya Nishikubo Atsushi Miyawaki Noninvasive monitoring of bilirubin photoisomer excretion during phototherapy Scientific Reports |
| title | Noninvasive monitoring of bilirubin photoisomer excretion during phototherapy |
| title_full | Noninvasive monitoring of bilirubin photoisomer excretion during phototherapy |
| title_fullStr | Noninvasive monitoring of bilirubin photoisomer excretion during phototherapy |
| title_full_unstemmed | Noninvasive monitoring of bilirubin photoisomer excretion during phototherapy |
| title_short | Noninvasive monitoring of bilirubin photoisomer excretion during phototherapy |
| title_sort | noninvasive monitoring of bilirubin photoisomer excretion during phototherapy |
| url | https://doi.org/10.1038/s41598-022-16180-9 |
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