The Extent of Intracellular Accumulation of Bilirubin Determines Its Anti- or Pro-Oxidant Effect

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F20%3A10418127" target="_blank" >RIV/00216208:11110/20:10418127 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/20:10418127

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=lG_8VoOECJ" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=lG_8VoOECJ</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms21218101" target="_blank" >10.3390/ijms21218101</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The Extent of Intracellular Accumulation of Bilirubin Determines Its Anti- or Pro-Oxidant Effect

Popis výsledku v původním jazyce

Background: Severe hyperbilirubinemia can cause permanent neurological damage in particular in neonates, whereas mildly elevated serum bilirubin protects from various oxidative stress-mediated diseases. The present work aimed to establish the intracellular unconjugated bilirubin concentrations (iUCB) thresholds differentiating between anti- and pro-oxidant effects. Methods: Hepatic (HepG2), heart endothelial (H5V), kidney tubular (HK2) and neuronal (SH-SY5Y) cell lines were exposed to increasing concentration of bilirubin. iUCB, cytotoxicity, intracellular reactive oxygen species (ROS) concentrations, and antioxidant capacity (50% efficacy concentration (EC50)) were determined. Results: Exposure of SH-SY5Y to UCB concentration &gt; 3.6 mu M (iUCB of 25 ng/mg) and &gt;15 mu M in H5V and HK2 cells (iUCB of 40 ng/mg) increased intracellular ROS production (p &lt; 0.05). EC50 of the antioxidant activity was 21 mu M (iUCB between 5.4 and 21 ng/mg) in HepG2 cells, 0.68 mu M (iUCB between 3.3 and 7.5 ng/mg) in SH-SY5Y cells, 2.4 mu M (iUCB between 3 and 6.7 ng/mg) in HK2 cells, and 4 mu M (iUCB between 4.7 and 7.5 ng/mg) in H5V cells. Conclusions: In all the cell lines studied, iUCB of around 7 ng/mg protein had antioxidant activities, while iUCB &gt; 25 ng/mg protein resulted in a prooxidant and cytotoxic effects. UCB metabolism was found to be cell-specific resulting in different iUCB.

Název v anglickém jazyce

The Extent of Intracellular Accumulation of Bilirubin Determines Its Anti- or Pro-Oxidant Effect

Popis výsledku anglicky

Background: Severe hyperbilirubinemia can cause permanent neurological damage in particular in neonates, whereas mildly elevated serum bilirubin protects from various oxidative stress-mediated diseases. The present work aimed to establish the intracellular unconjugated bilirubin concentrations (iUCB) thresholds differentiating between anti- and pro-oxidant effects. Methods: Hepatic (HepG2), heart endothelial (H5V), kidney tubular (HK2) and neuronal (SH-SY5Y) cell lines were exposed to increasing concentration of bilirubin. iUCB, cytotoxicity, intracellular reactive oxygen species (ROS) concentrations, and antioxidant capacity (50% efficacy concentration (EC50)) were determined. Results: Exposure of SH-SY5Y to UCB concentration &gt; 3.6 mu M (iUCB of 25 ng/mg) and &gt;15 mu M in H5V and HK2 cells (iUCB of 40 ng/mg) increased intracellular ROS production (p &lt; 0.05). EC50 of the antioxidant activity was 21 mu M (iUCB between 5.4 and 21 ng/mg) in HepG2 cells, 0.68 mu M (iUCB between 3.3 and 7.5 ng/mg) in SH-SY5Y cells, 2.4 mu M (iUCB between 3 and 6.7 ng/mg) in HK2 cells, and 4 mu M (iUCB between 4.7 and 7.5 ng/mg) in H5V cells. Conclusions: In all the cell lines studied, iUCB of around 7 ng/mg protein had antioxidant activities, while iUCB &gt; 25 ng/mg protein resulted in a prooxidant and cytotoxic effects. UCB metabolism was found to be cell-specific resulting in different iUCB.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/NV18-07-00342" target="_blank" >NV18-07-00342: Studium degradačních produktů bilirubinu vznikajících při fototerapii novorozenecké žloutenky</a><br>

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

International Journal of Molecular Sciences [online]

ISSN

1422-0067

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

21

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

17

Strana od-do

8101

Kód UT WoS článku

000589039400001

EID výsledku v databázi Scopus

2-s2.0-85095578945