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Ghanayem BI, Ahmed AE: Acrylonitrile-induced gastrointestinal hemorrhage and the effects of metabolism modulation in rats. Toxicol Appl Pharmacol. 1983 Apr;68(2):290-6.
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. |
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