Urinary mercapturic acid diastereoisomers in rats subchronically exposed to styrene and ethanol

Teresa Coccini, Luciano Maestri, Francesco S. Robustelli Della Cuna, Li Bin, Lucio G. Costa, Luigi Manzo

Research output: Contribution to journalArticle

Abstract

Styrene is stereoselectively oxidized by cytochrome P450 to its reactive metabolite, styrene oxide. The (R)- and (S)-enantiomers of styrene oxide can be conjugated with glutathione (GSH) to both (R)- and (S)-diastereoisomers of the specific mercapturic acids, N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2). Several investigations have indicated different toxic potential of the (R)- and (S)-configurations of styrene oxide and its GSH- and N-acetyl-conjugates. In this study the mercapturic acid diastereoisomers were measured in the urine of rats exposed to styrene in combination with ethanol, a good inducer of styrene metabolism. Male Sprague-Dawley rats were given an isocaloric liquid diet containing ethanol (5% w/v) for 3 weeks. Starting from the 2nd week, the animals were also exposed to styrene vapours (300 ppm, 6 h/day, 5 days/week) in a dynamic exposure chamber. Both the (R)- and (S)-diastereoisomers of the M1 and M2 as well as the conventional biomarkers, mandelic acid (MA) and phenylglyoxylic acid (PGA) were measured in urinary samples. Approximately 30 and 25% reduction of the levels of brain non-protein sulfhydryls (NPS) was observed in the animals given styrene and ethanol, respectively, while the combined ethanol and styrene treatment resulted in a 60% decrease. Ethanol consumption also resulted in higher urinary levels of the M1-R, M1-S and M2 metabolites associated with increased M1-R/S ratio and higher urinary MA excretion compared to animals treated with styrene. These results suggest that the urinary mercapturic acid diastereoisomers may be used as a noninvasive tool to examine stereoselective patterns of styrene metabolism in vivo, as well as their alterations caused by ethanol. These compound-specific mercapturic acids may also be valuable indicators of styrene-induced disorders of GSH homeostasis in nonaccessible organs.

Original languageEnglish
Pages (from-to)736-741
Number of pages6
JournalArchives of Toxicology
Volume70
Issue number11
DOIs
Publication statusPublished - 1996

Fingerprint

Styrene
Acetylcysteine
Rats
Ethanol
styrene oxide
Animals
Metabolites
Metabolism
Cysteine
Enantiomers
Poisons
Biomarkers
Nutrition
Cytochrome P-450 Enzyme System
Glutathione
Sprague Dawley Rats
Brain
Homeostasis
Vapors
Urine

Keywords

  • Biomarkers
  • Ethanol
  • Mercapturic acid diastereoisomers
  • Styrene

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Urinary mercapturic acid diastereoisomers in rats subchronically exposed to styrene and ethanol. / Coccini, Teresa; Maestri, Luciano; Robustelli Della Cuna, Francesco S.; Bin, Li; Costa, Lucio G.; Manzo, Luigi.

In: Archives of Toxicology, Vol. 70, No. 11, 1996, p. 736-741.

Research output: Contribution to journalArticle

Coccini, T, Maestri, L, Robustelli Della Cuna, FS, Bin, L, Costa, LG & Manzo, L 1996, 'Urinary mercapturic acid diastereoisomers in rats subchronically exposed to styrene and ethanol', Archives of Toxicology, vol. 70, no. 11, pp. 736-741. https://doi.org/10.1007/s002040050334
Coccini, Teresa ; Maestri, Luciano ; Robustelli Della Cuna, Francesco S. ; Bin, Li ; Costa, Lucio G. ; Manzo, Luigi. / Urinary mercapturic acid diastereoisomers in rats subchronically exposed to styrene and ethanol. In: Archives of Toxicology. 1996 ; Vol. 70, No. 11. pp. 736-741.
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