Biological fate of styrene oxide adducts with globin: Elimination of cleavage products in the rat urine

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F16%3A43902182" target="_blank" >RIV/60461373:22310/16:43902182 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/75010330:_____/16:00011494

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.toxlet.2016.08.022" target="_blank" >http://dx.doi.org/10.1016/j.toxlet.2016.08.022</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.toxlet.2016.08.022" target="_blank" >10.1016/j.toxlet.2016.08.022</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Biological fate of styrene oxide adducts with globin: Elimination of cleavage products in the rat urine

Popis výsledku v původním jazyce

The in vivo fate of globin adducts with styrene 7,8-oxide (SO), an electrophilic metabolic intermediate of styrene, was studied in male Wistar rats dosed intraperitoneally with racemic SO, 100 mg/kg b.w. Regioisomeric hydroxy(phenyl)ethyl (HPE) adducts at Cys, N-terminal Val, Lys and His in globin were determined and their elimination from blood was followed during 60 days, corresponding to life span of rat erythrocytes. In the rat urine, N?-acetylated products of hydrolytic cleavage of the HPE adducts with Cys, Lys and His were determined. On the first day post-exposure, abundant N?-acetyl-HPE-Cys adducts (mercapturic acids) formed via direct conjugation of SO with hepatic glutathione were excreted rapidly, but then a much slower phase of elimination reflecting formation of N?-acetyl-HPE-Cys via cleavage of the adducted globin was observed. A two-phase elimination occurred also in urinary N?-acetyl-HPE adducts with His and Lys. While a decline by 75?85% during the first 7 days post-exposure most likely reflected elimination of adducted albumin, the subsequent slow decline until day 60 corresponded to elimination kinetics of the adducted globin. Thus, the study not only provided original data on the fate of SO-globin adducts but also allowed to reveal general toxicokinetics properties of the urinary cleavage products as a novel type of chemical exposure biomarkers. ? 2016 Elsevier Ireland Ltd

Název v anglickém jazyce

Biological fate of styrene oxide adducts with globin: Elimination of cleavage products in the rat urine

Popis výsledku anglicky

The in vivo fate of globin adducts with styrene 7,8-oxide (SO), an electrophilic metabolic intermediate of styrene, was studied in male Wistar rats dosed intraperitoneally with racemic SO, 100 mg/kg b.w. Regioisomeric hydroxy(phenyl)ethyl (HPE) adducts at Cys, N-terminal Val, Lys and His in globin were determined and their elimination from blood was followed during 60 days, corresponding to life span of rat erythrocytes. In the rat urine, N?-acetylated products of hydrolytic cleavage of the HPE adducts with Cys, Lys and His were determined. On the first day post-exposure, abundant N?-acetyl-HPE-Cys adducts (mercapturic acids) formed via direct conjugation of SO with hepatic glutathione were excreted rapidly, but then a much slower phase of elimination reflecting formation of N?-acetyl-HPE-Cys via cleavage of the adducted globin was observed. A two-phase elimination occurred also in urinary N?-acetyl-HPE adducts with His and Lys. While a decline by 75?85% during the first 7 days post-exposure most likely reflected elimination of adducted albumin, the subsequent slow decline until day 60 corresponded to elimination kinetics of the adducted globin. Thus, the study not only provided original data on the fate of SO-globin adducts but also allowed to reveal general toxicokinetics properties of the urinary cleavage products as a novel type of chemical exposure biomarkers. ? 2016 Elsevier Ireland Ltd

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FP - Ostatní lékařské obory

OECD FORD obor

—

Projekt

<a href="/cs/project/NT13401" target="_blank" >NT13401: Degradační produkty proteinových aduktů v moči jako nový typ biomarkerů v toxikologii</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Toxicology Letters

ISSN

0378-4274

e-ISSN

—

Svazek periodika

261

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

6

Strana od-do

26-31

Kód UT WoS článku

000385529600003

EID výsledku v databázi Scopus

2-s2.0-84988700510