Thioctic acid protection against ethanol-induced gastric mucosal lesions involves sulfhydryl and prostaglandin...

Thioctic acid, a sulfhydryl agent, given orally macroscopically protected the gastric mucosa from 96% ethanol-induced lesions in a dose-and time dependent fashion. The inhibition of the lesions was 56.0 and 90.3% at doses of 25 and 50 mg/kg, respectively. The duration of its protective effect was approximately 120 minutes. Histopathologically, the oral administration of thioctic acid prevented necrotic mucosal lesions in the deeper part of the mucosa but did not protect the surface epithelial cells against ethanol challenge. Gastric motility measured by a balloon method, was dose-dependently inhibited by the oral administration of thioctic acid. Thioctic acid protection was suppressed by pretreatment with indomethacin (30 mg/kg), a cyclooxygenase inhibitor, and iodoacetamide (100 mg/kg), a sulfhydryl blocker. The gastric motility inhibited by oral thioctic acid was not reversed by indomethacin or iodoacetamide. These doses of indomethacin or iodomethamide were administered because previously they had been used to suppress endogenous prostaglandins, and nonprotein sulfhydryls of the gastric mucosa, respectively. There was an increase in the fluid volume retained in the gastric lumen for thioctic acid (50 mg/kg) at 30, 60, 90, and 120 minutes after administration. There was an increase in the mucus volume retained in the gastric lumen for thioctic acid (50, 25 mg/kg) at 120 minutes after administration. The lesion area in the rats treated with 70 microliters of vehicle and in the rats treated with 250 microliters of vehicle were significantly higher than in the rats treated with 450 microliters of vehicle. The present study suggests that thioctic acid administered orally, offered protection to the rat gastric mucosa against 96% ethanol-induced lesions. This protective effect appears to be dependent on prostaglandin-and sulfhydryl-sensitive mechanisms, together with an increase in both the fluid volume and the mucus volume retained in the gastric lumen, and is not associated with the inhibition of gastric motor activity.