Role of sulfhydryls and early vascular lesions in gastric mucosal injury.
This paper reviews the recently discovered role of sulfhydryls and early vascular injury in the pathogenesis of acute gastric mucosal injury. In the rat ethanol caused a dose-dependent decrease in nonprotein sulfhydryl concentration in the gastric mucosa within 1-5 min following an intragastric dose. These biochemical changes were accompanied by increased vascular permeability in the glandular stomach as revealed by the measurement of extravasated Evans blue injected i.v. prior to the administration of ethanol. Morphologic evidence of vascular injury was provided by labelling of damaged blood vessels in the stomach following the i.v. administration of colloidal particles in the form of india ink or monastral blue. The functional and structural damage to capillaries and venules in the glandular stomach was also maximal within 1-6 min after 1 ml of 75 or 100% ethanol given orally. Pretreatment with sulfhydryl (SH) containing drugs (e.g., L-cysteine, N-acetyl-L-cysteine, cysteamine, dimercaprol) or prostaglandin (PG) F2 beta prevented the ethanol-induced increase in vascular permeability, the labelling of blood vessels with vascular tracers, and the subsequent haemorrhagic erosions. The desquamation of superficial epithelial cells, however, was not markedly modified by either SH or PG compounds. This organoprotective effect of SH and PG drugs was virtually counteracted in adrenalectomized rats that exhibited "vascular fragility". Glucocorticoid treatment restored the response of adrenalectomized animals. Thus, a SH- and glucocorticoid-sensitive early vascular injury seems to be of major significance in the pathogenesis of haemorrhagic gastric erosions and SH-containing compounds represent a new group of cytoprotective or organoprotective agents.
D000818:Animals; D002198:Capillary Fragility / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D010438:Peptic Ulcer Hemorrhage / Q000378:metabolism / Q000517:prevention & control; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000378:metabolism / Q000517:prevention & control*; D013438:Sulfhydryl Compounds / Q000378:metabolism / Q000494:pharmacology*; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; D000431:Ethanol