Urinary metabolites of [1,2,3-13C]acrylonitrile in rats and mice detected by carbon-13 nuclear magnetic resonance spectroscopy

Fennell, Timothy R.; Kedderis, Gregory L.; Sumner, Susan

doi:10.1021/tx00024a013

Cited by 76 publications

(80 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…An increase in metabolism was not indicated for rats because the percentage of AM or AN dose excreted was not significantly different (p > 0.12, AN; p > 0.08, AM) following either 1 day (49% AN; 39% AM) or 5 days (60% AN, 48% AM) of coadministration. Previous investigations (15) in which 10 or 30 mg/ kg [1,2,3-13 C]AN was administered to mice or rats, respectively, resulted in the excretion of ∼55% of the total dose for either species within 24 h after administration, consistent with the percentage of AN dose excreted (48%) following a single coadministration of AM and AN. Rats and mice administered 50 mg/kg [1,2,3-13 C]AM excrete approximately 50% of the dose in the urine within 24 h (13), consistent with that determined for mice (55% of the AM dose) administered a single dose of AM and AN but higher than that determined for rats (39% of the AM dose).…”

Section: Resultssupporting

confidence: 71%

See 1 more Smart Citation

Urinary Metabolites from F344 Rats and B6C3F1 Mice Coadministered Acrylamide and Acrylonitrile for 1 or 5 Days

Sumner

Selvaraj

Nauhaus

et al. 1997

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

The purpose of this study was to examine the feasibility of using 13C NMR spectroscopy to analyze urinary metabolites produced following coadministration of two structurally similar carbon-13-labeled compounds to rodents. Acrylonitrile (AN) and acrylamide (AM) are used in the chemical industry to manufacture plastics and polymers. These compounds are known to produce carcinogenic, reproductive, or neurotoxic effects in laboratory animals. The potential for human exposure to AN and AM occurs in manufacturing facilities and environmentally. Male F344 rats and B6C3F1 mice were coadministered po [1,2,3-13C]AN (16-17 mg/kg) and [1,2,3-13C]AM (21-22 mg/kg) after 0 or 4 days of administration of unlabeled AN or AM. Urine was collected for 24 h following administration of the 13C-labeled compounds and analyzed by 13C NMR spectroscopy. Rats and mice excreted metabolites derived from glutathione (GSH) conjugation with AM or AN or derived from GSH conjugation with the epoxides cyanoethylene oxide (CEO) or glycidamide (GA). GA and its hydrolysis product were also detected in the urine of rats and mice. For mice, an increased urinary excretion of total AN- and total AM-derived metabolites (p < 0.05) on repeated coadministration suggested a possible increase in metabolism via oxidation. In addition, mice had an increased (p < 0.05) percentage of dose excreted as metabolites derived from GSH conjugation with AM, AN, CEO, or GA after five exposures as compared with one exposure that may be related to a significant increase in the synthesis of GSH or an increase in glutathione transferase activity. The only significant (p < 0.05) increase between one and five exposures for the rat was in the percentage of metabolites produced following conversion of AM to GA. The use of 13C NMR spectroscopy has provided a powerful methodology for elucidation of the metabolism of two 13C-labeled chemicals administered simultaneously.

show abstract

Section: Resultssupporting

confidence: 71%

“…The percentage of the administered dose produced from a Metabolites that give rise to signals with these chemical shifts were characterized in previous studies in which rodents were administered po [ 13 C]AN (15) …”

Section: Resultsmentioning

confidence: 99%

Urinary Metabolites from F344 Rats and B6C3F1 Mice Coadministered Acrylamide and Acrylonitrile for 1 or 5 Days

Sumner

Selvaraj

Nauhaus

et al. 1997

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Several studies have indicated the role of oxidative stress in the toxicity of ACN. For instance, the major pathway of ACN elimination is its conjugation with GSH to form mercapturic acid through the GST activity [7]. By depleting GSH, ACN may decrease the antioxidant levels of the cells leading to an overall increase in intracellular reactive oxygen species (ROS) and oxidative damage.…”

Section: Discussionmentioning

confidence: 99%

“…It was hypothesized that CEO metabolism via epoxide hydrolase is the primary pathway for cyanide formation [2]. Glutathione (GSH) conjugation has been shown to be depleted following ACN treatment in vivo and may decrease the antioxidant capacity of the cells resulting in an overall increase in intracellular reactive oxygen species (ROS) and oxidative damage [7][8][9]. Cyanide has been shown to induce oxidative stress (lipid peroxidation) in the brain of acutely treated mice and in cell lines [10,11].…”

Section: Introductionmentioning

confidence: 99%

Hesperidin, an antioxidant flavonoid, prevents acrylonitrile‐induced oxidative stress in rat brain

El-Sayed

Abo-Salem

Abd-Ellah

et al. 2008

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Acrylonitrile (ACN) is a volatile, toxic liquid used as a monomer in the manufacture of synthetic rubber, styrene plastics, acrylic fiber, and adhesives. ACN is a potent neurotoxin. A role for free radical mediated lipid peroxidation in the toxicity of ACN has been suggested. We examined the ability of hesperidin, an antioxidant flavonoid, to attenuate ACN-induced alterations in lipid peroxidation in rat brains. The daily oral administration of ACN to male albino rats in a dose of 50 mg/kg bwt for a period of 28 days produced a significant elevation in brain lipid peroxides measured as malondialdehyde (MDA) amounting to 107%, accompanied by a marked decrease in brain-reduced glutathione (GSH) content reaching 63%. In addition, ACN administration resulted in significant reductions in the enzymatic antioxidant parameters of brain; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione-S-transferase (GST) recording 43%, 64%, 52%, and 43%, respectively. On the other hand, pretreatment with hesperidin and its coadministration with ACN once daily in a dose of 200 mg/kg bwt i.p. for 28 days ameliorated ACN-induced alterations in brain lipid peroxidation. These results suggest that hesperidin may have a beneficial role against ACN-induced oxidative stress in the brain; an effect that is mainly attributed to the antioxidant property of hesperidin.

show abstract

“…AN is initially metabolized by two pathways (Fig. 1): (1) conjugation with glutathione, either through catalysis with a cytosolic glutathione-S-transferase (GST) or nonenzymatically and (2) epoxidation by microsomal cytochrome P450 (particularly CYP2E1) forming 2-cyanoethylene oxide (CEO) (Burka et al, 1994;Dahl and Waruszewski, 1989;Fennell et al, 1991;Gargas et al, 1995;Sumner et al, 1999). The primary metabolites from both pathways are subject to further metabolism.…”

Section: Data From Mechanistic Studiesmentioning

confidence: 99%

Cancer dose–response assessment for acrylonitrile based upon rodent brain tumor incidence: Use of epidemiologic, mechanistic, and pharmacokinetic support for nonlinearity

Kirman

Gargas

Marsh

et al. 2005

Regulatory Toxicology and Pharmacology

View full text Add to dashboard Cite

Urinary metabolites of [1,2,3-13C]acrylonitrile in rats and mice detected by carbon-13 nuclear magnetic resonance spectroscopy

Cited by 76 publications

References 28 publications

Urinary Metabolites from F344 Rats and B6C3F1 Mice Coadministered Acrylamide and Acrylonitrile for 1 or 5 Days

Urinary Metabolites from F344 Rats and B6C3F1 Mice Coadministered Acrylamide and Acrylonitrile for 1 or 5 Days

Hesperidin, an antioxidant flavonoid, prevents acrylonitrile‐induced oxidative stress in rat brain

Cancer dose–response assessment for acrylonitrile based upon rodent brain tumor incidence: Use of epidemiologic, mechanistic, and pharmacokinetic support for nonlinearity

Contact Info

Product

Resources

About