Acrylonitrile-induced gastric mucosal necrosis: role of gastric glutathione.
Acrylonitrile [vinyl cyanide (VCN)] induces acute hemorrhagic focal superficial gastric mucosal necrosis or gastric erosions. In this report the authors have studied the mechanism of the VCN-induced gastric erosions. VCN-induced gastric lesions are coupled with a marked decrease of gastric reduced glutathione (GSH) concentration. Pretreatment of rats with various metabolic modulators (cytochrome P-450 monooxygenase and GSH) before VCN demonstrated that there is an inverse and highly significant correlation between gastric GSH concentration and the VCN-induced gastric erosions. Pretreatment of rats with sulfhydryl-containing compounds protected against the VCN-induced gastric necrosis and blocked the VCN-induced gastric GSH depletion. Furthermore, pretreatment of rats with atropine, which blocks muscarinic receptors, protected rats against the VCN-induced gastric erosions. The working hypothesis is that depletion and/or inactivation of critical endogenous sulfhydryl groups causes configurational changes of cholinergic receptors and increases agonist binding affinity, which, among other actions, leads to the causation of gastric mucosal erosions.
D000181:Acrylonitrile / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D003543:Cysteamine / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism*; D008297:Male; D008298:Maleates / Q000494:pharmacology; D009336:Necrosis / Q000139:chemically induced / Q000378:metabolism; D009570:Nitriles / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D008298:Maleates; D009570:Nitriles; D003543:Cysteamine; D003577:Cytochrome P-450 Enzyme System; C014476:diethyl maleate; D005978:Glutathione; D000181:Acrylonitrile