Biological fate of styrene oxide adducts with globin: Elimination of cleavage products in the rat urine. (2nd November 2016)

• Record Type: Journal Article
• Authors: Mráz, Jaroslav; Hanzlíková, Iveta; Dušková, Šárka; Dabrowská, Ludmila; Chrástecká, Hana; Vajtrová, Radka; Linhart, Igor
• Is Part Of: Toxicology letters. Volume 261(2016)
• Page Start: 26
• Page End: 31
• Publication Date: 2016-11-02
• Subjects: Styrene oxide -- Globin adducts -- Urinary adducts -- Hydroxy(phenyl)ethyl mercapturic acids -- Biological monitoring; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2016.08.022
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Styrene oxide produces covalent adducts at some amino acids in rat globin in vivo . On hydrolytic cleavage of globin these amino acid adducts are eliminated in urine. Excretion kinetics of the urinary adducts reflects the erythrocyte life span. Abstract: 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, Nα -acetylated products of hydrolytic cleavage of the HPE adducts with Cys, Lys and His were determined. On the first day post-exposure, abundant Nα -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 Nα -acetyl-HPE-Cys via cleavage of the adducted globin was observed. A two-phase elimination occurred also in urinary Nα -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.