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BI Ghanayem, PJ Boor and AE Ahmed
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.
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