The role of non-protein sulphydryls in the protective effects of antioxidants against ethanol-induced vascular permeability changes in the rat stomach

Abstract

Increased vascular permeability has been reported to preceed the development of ethanol-induced gastric lesions. Both generation of oxygen-derived free radicals and depletion of non-protein sulphydryls may be involved in the ethanol-induced vascular permeability. Thus, this study aimed to examine the effect of antioxidants, allopurinol and dimethylsulphoxide, and a sulphydryl blocker, N-ethylmaleimide, on ethanol-induced vascular permeability changes and to evaluate the possible interactions between antioxidants and endogenous sulphydryls. Extravasation of intravenously administered Evans blue into the stomach of rats following 30 min exposure to ethanol was used as an indicator of vascular permeability. The glandular non-protein sulphydryl and extravasated Evans blue were determined spectrophotometrically. Increased vascular permeability and a significant depletion of non-protein sulphydryl contents of the gastric mucosa were observed following 30 min exposure to 50% ethanol. Treatment with N-ethylmaleimide (50 mg/kg subcutaneously) caused enhancement of ethanol-induced vascular permeability and further depletion of non-protein sulphydryls. Intraperitoneal pretreatment with either allopurinol (12.5-50 mg/kg) or dimethylsulphoxide (20-40 mg/kg) attenuated ethanol-induced vascular permeability changes and restored the non-protein sulphydryl levels towards control. In contrast, treatment with N-ethylmaleimide before allopurinol (50 mg/kg) or dimethylsulphoxide (40 mg/kg) reduced the protective effect of both and are also associated with corresponding depletion of non-protein sulphydryl contents. These results suggest that oxygen-derived free radicals may be involved in the pathogenesis of ethanol-induced vascular permeability changes and endogenous sulphydryls may facilitate and mediate beneficial effects of antioxidants.