Bilirubin-induced cell death during continuous and intermittent phototherapy and in the dark

Roll, Ellen

doi:10.1080/08035250510032646

Cited by 11 publications

(5 citation statements)

References 19 publications

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“…It is generally believed that bilirubin photoisomers are non-toxic; however, no clear evidence for this viewpoint exists, and insufficient data about bilirubin PI's biological effects have thus far been provided. [ 16 – 23 ]. Of note is the fact that in none of these studies were the pure forms of the bilirubin photoderivatives used, most likely because of their complicated isolation and handling.…”

Section: Discussionmentioning

confidence: 99%

“…Nothing is known about whether bilirubin PI may affect the bilirubin-albumin interaction. Previous studies on the biological effects of bilirubin photoproducts [ 16 – 23 ] suffered from a major limitation (insufficient purity of the bilirubin photoproducts), as well as inconsistent study designs. Thus, there is still uncertainty on the potential toxicity of bilirubin breakdown products not only for the central nervous system, but also other organs.…”

Section: Introductionmentioning

confidence: 99%

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The Biological Effects of Bilirubin Photoisomers

et al. 2016

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Although phototherapy was introduced as early as 1950’s, the potential biological effects of bilirubin photoisomers (PI) generated during phototherapy remain unclear. The aim of our study was to isolate bilirubin PI in their pure forms and to assess their biological effects in vitro. The three major bilirubin PI (ZE- and EZ-bilirubin and Z-lumirubin) were prepared by photo-irradiation of unconjugated bilirubin. The individual photoproducts were chromatographically separated (TLC, HPLC), and their identities verified by mass spectrometry. The role of Z-lumirubin (the principle bilirubin PI) on the dissociation of bilirubin from albumin was tested by several methods: peroxidase, fluorescence quenching, and circular dichroism. The biological effects of major bilirubin PI (cell viability, expression of selected genes, cell cycle progression) were tested on the SH-SY5Y human neuroblastoma cell line. Lumirubin was found to have a binding site on human serum albumin, in the subdomain IB (or at a close distance to it); and thus, different from that of bilirubin. Its binding constant to albumin was much lower when compared with bilirubin, and lumirubin did not affect the level of unbound bilirubin (Bf). Compared to unconjugated bilirubin, bilirubin PI did not have any effect on either SH-SY5Y cell viability, the expression of genes involved in bilirubin metabolism or cell cycle progression, nor in modulation of the cell cycle phase. The principle bilirubin PI do not interfere with bilirubin albumin binding, and do not exert any toxic effect on human neuroblastoma cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Biological Effects of Bilirubin Photoisomers

et al. 2016

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“…In this study, the proportion of the apoptotic cells in the epithelium of the small intestine was 1.7% in the control group, and grew to 3.1 and 6.2% in the LED group and the conventional group, respectively. Phototherapy increases apoptosis due to cell damage depending on wavelength [11,12]. The two lamps, a turquoise (green) fluorescent phototherapy lamp (490 nm) and a conventional blue phototherapy lamp (450 nm), were similar in the formation of therapeutically relevant photoproducts, but the blue lamp showed potential in forming more severe cellular damage by the difference of wavelength [12].…”

Section: Discussionmentioning

confidence: 99%

“…Roll and Christensen measured apoptotic or necrotic cells induced by phototherapy using a mouse lymphoma cell line, and concluded that the emitted light increased apoptosis and necrosis due to photo-oxidation and cell damage in vitro [11,12].…”

Section: Introductionmentioning

confidence: 99%

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Apoptosis in the small intestine of neonatal rat using blue light-emitting diode devices and conventional halogen-quartz devices in phototherapy

et al. 2008

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Phototherapy is the most frequently used treatment for the neonatal jaundice. However, recent papers report that phototherapy increased apoptosis in peripheral mononuclear leukocytes in vivo and in mouse lymphoma cell line in vitro. We have investigated the cytotoxicity of phototherapy on the small intestine of neonatal rat using conventional halogen-quartz device (conventional device) and blue light-emitting device (LED device) by measuring apoptotic cells. Four-day-old male Wistar rats were divided into three groups as follows: group 1, exposure to conventional device for 72 h; group 2, exposure to LED device for 72 h; and group 3, control (without phototherapy). After light exposure, the small intestine was examined for apoptosis. Apoptotic cells were detected by the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay, by immunohistochemistry for caspase-3 and by transmission electron microscopy. The proportion of positive cells by the TUNEL method in the epithelium of the small intestine was 6.2, 3.1 and 1.7% in the conventional device group, the LED device group and the control group, respectively. The apoptotic cells of the conventional device group is significantly higher than the LED device group (P < 0.01) and that of the LED device group was higher than that of the control group (P < 0.05). We suspected that phototherapy induced apoptosis in neonatal small intestine and the conventional device introduces more apoptosis than the LED device.

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