In Vivo Biotransformation and Biliary Excretion of 1-14C-acrylonitrile in Rats

Overview

Journal Arch Toxicol

Specialty Toxicology

Date 1982 Jul 1

PMID 7125911

Citations 2

Authors

B I Ghanayem

A E Ahmed

Affiliations

Soon will be listed here.

Abstract

1-14C-Acrylonitrile (VCN) was give orally to rats, 27% of the given dose was excreted in bile in 6 h. When 1-14C-VCN was given to overnight fasted or cobaltous chloride treated rats, a significant increase in the biliary excretion occurred. Pretreatment of rats with phenobarbital produced no change, while diethyl maleate pretreatment significantly decreased the portion of the dose excreted in bile in 6 h. Four metabolites of 1-14C-VCN have been isolated from the collected bile, and characterized. The two major biliary metabolites were found to be glutathione (GSH) conjugates of VCN, indicating the importance of GSH in VCN biotransformation.

Citing Articles

Modulation of acrylonitrile-induced embryotoxicity in vitro by glutathione depletion.

Saillenfait A, Payan J, Langonne I, Beydon D, Grandclaude M, Sabate J Arch Toxicol. 1993; 67(3):164-72.

PMID: 8494495 DOI: 10.1007/BF01973303.

Comparative metabolism and disposition of acrylonitrile and methacrylonitrile in rats.

Burka L, Sanchez I, Ahmed A, Ghanayem B Arch Toxicol. 1994; 68(10):611-8.

PMID: 7857200 DOI: 10.1007/BF03208340.

References

MALTONI C, Ciliberti A, Di Maio V . Carcinogenicity bioassays on rats of acrylonitrile administered by inhalation and by ingestion. Med Lav. 1977; 68(6):401-11. View

Abreu M, Ahmed A . Metabolism of acrylonitrile to cyanide. In vitro studies. Drug Metab Dispos. 1980; 8(6):376-9. View

Knight R, Young L . Biochemical studies of toxic agents. 11. The occurrence of premercapturic acids. Biochem J. 1958; 70(1):111-9. PMC: 1196634. DOI: 10.1042/bj0700111. View

Cantrell E, Marshall M, McLemore T, Ghanayem B, Busbee D . Secondary metabolism of benzo(a)pyrene in human cells. Proc West Pharmacol Soc. 1979; 22:273-6. View

Penke B, Ferenczi R, Kovacs K . A new acid hydrolysis method for determining tryptophan in peptides and proteins. Anal Biochem. 1974; 60(1):45-50. DOI: 10.1016/0003-2697(74)90129-8. View

Boyland E, Chasseaud L . Enzymes catalysing conjugations of glutathione with alpha-beta-unsaturated carbonyl compounds. Biochem J. 1968; 109(4):651-61. PMC: 1186951. DOI: 10.1042/bj1090651. View

Boyland E, Chasseaud L . Enzyme-catalysed conjugations of glutathione with unsaturated compounds. Biochem J. 1967; 104(1):95-102. PMC: 1270549. DOI: 10.1042/bj1040095. View

Murray F, Schwetz B, Nitschke K, John J, Norris J, GEHRING P . Teratogenicity of acrylonitrile given to rats by gavage or by inhalation. Food Cosmet Toxicol. 1978; 16(6):547-51. DOI: 10.1016/s0015-6264(78)80222-3. View

Langvardt P, Putzig C, Braun W, Young J . Identification of the major urinary metabolites of acrylonitrile in the rat. J Toxicol Environ Health. 1980; 6(2):273-82. DOI: 10.1080/15287398009529851. View

10.

Szabo S, Bailey K, Boor P, Jaeger R . Acrylonitrile and tissue glutathione: differential effect of acute and chronic interactions. Biochem Biophys Res Commun. 1977; 79(1):32-7. DOI: 10.1016/0006-291x(77)90056-0. View

11.

Vainio H, Makinen A . Styrene and acrylonitrile induced depression of hepatic nonprotein sulfhydryl content in various rodent species. Res Commun Chem Pathol Pharmacol. 1977; 17(1):115-24. View

12.

van Bladeren P, Delbressine L, Hoogeterp J, Beaumont A, Breimer D, van der Gen A . Formation of mercapturic acids from acrylonitrile, crotononitrile, and cinnamonitrile by direct conjugation and via an intermediate oxidation process. Drug Metab Dispos. 1981; 9(3):246-9. View

13.

Gut I, Nerudova J, Kopecky J, Holecek V . Acrylonitrile biotransformation in rats, mice, and chinese hamsters as influenced by the route of administration and by phenobarbital, SKF 525-A, cysteine, dimercaprol, or thiosulfate. Arch Toxicol. 1975; 33(2):151-61. DOI: 10.1007/BF00353240. View

14.

SASAME H, Boyd M . Paradoxical effects of cobaltous chloride and salts of other divalent metals on tissue levels of reduced glutathione and microsomal mixed-function oxidase components. J Pharmacol Exp Ther. 1978; 205(3):718-24. View

15.

Kopecky J, Gut I, Nerudova J, Zachardova D, Holecek V . Two routes of acrylonitrile metabolism. J Hyg Epidemiol Microbiol Immunol. 1980; 24(3):356-62. View

16.

OBerg M . Epidemiologic study of workers exposed to acrylonitrile. J Occup Med. 1980; 22(4):245-52. View