Acrylonitrile-induced gastrointestinal hemorrhage and the effects of metabolism modulation in rats.
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.
D000181:Acrylonitrile / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D007279:Injections, Subcutaneous; D008297:Male; D009570:Nitriles / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D009570:Nitriles; D003577:Cytochrome P-450 Enzyme System; D000181:Acrylonitrile