Acrylonitrile-induced gastrointestinal hemorrhage and the effects of metabolism modulation in rats.

Abstract

Acrylonitrile (VCN) is a heavily used monomer in plastic and fiber industries. Quantitatively, VCN-induced gastrointestinal hemorrhage is time and dose dependent and is not the result of a direct irritating action of VCN on gastric tissues. The effect of cytochrome P-450 enzymes inducers was studied. Pretreatment with phenobarbital decreased the VCN-induced GI blood loss (55%), while Aroclor 1254 drastically increased it (240%). VCN administration to rats treated with cobalt chloride or SKF 525A (cytochrome P-450 enzymes inhibitors) resulted in a significant protection against GI bleeding (10 and 40%, respectively). Treatment with diethylmaleate (a known depletor of reduced glutathione) prior to VCN administration, produced no significant change in the VCN-induced GI bleeding. Potassium cyanide (KCN) administration to rats failed to produce significant GI bleeding. These results indicate that metabolic activation of the VCN molecule, to a metabolite(s) other than cyanide by the cytochrome P-450 enzymes, is a prerequisite for VCN to induce gastric hemorrhage.

• Authors: B I Ghanayem, A E Ahmed
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 68 Issue 2 Pg. 290-6 (Apr 1983) ISSN: 0041-008X [Print] United States
• PMID: 6602400 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Nitriles
• Cytochrome P-450 Enzyme System
• Acrylonitrile

Topics

• Acrylonitrile (toxicity)
• Administration, Oral
• Animals
• Cytochrome P-450 Enzyme System (biosynthesis)
• Enzyme Induction (drug effects)
• Gastrointestinal Hemorrhage (chemically induced)
• Injections, Subcutaneous
• Male
• Nitriles (toxicity)
• Rats
• Rats, Inbred Strains