Sulphydryl blocker induced gastric damage is ameliorated by scavenging of free radicals.
BACKGROUND
Sulphydryl compounds and nitric oxide are essential in maintaining gastric mucosal integrity.


OBJECTIVE
To characterise the gastric damage induced by a sulphydryl blocker, to evaluate the role of nitric oxide in its pathogenesis, and to reveal its possible prevention by scavenging of free radicals.


METHODS
Gastritis was induced in rats by addition of iodoacetamide (0.1%) to the drinking water, with and without daily intragastric administration of TEMPOL. After death, the stomach was resected, washed, lesion area assessed, and mucosal inflammatory mediators, myeloperoxidase and nitric oxide synthase activities were determined.


RESULTS
Administration of iodoacetamide induced gastric mucosal erosions present for up to two weeks. Myeloperoxidase activity was increased for up to seven days and nitric oxide synthase activity was significantly decreased for up to 14 days. Treatment for seven days with the free radical scavenger, TEMPOL, decreased by 68% the damage induced by iodoacetamide.


CONCLUSIONS
Gastric damage induced by iodoacetamide, a sulphydryl alkylator, accompanied by inhibition of nitric oxide synthase activity shows the important contribution of sulphydryl compounds and nitric oxide to the maintenance of gastric mucosal integrity. Nitric oxide donation and scavenging of free radicals may be a novel approach to prevent gastric damage.
Karmeli
F
F
Department of Medicine, Hadassah University Hospital, Mount Scopus, Israel.
Okon
E
E
Rachmilewitz
D
D
D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D015232:Dinoprostone / Q000032:analysis; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D005756:Gastritis / Q000139:chemically induced / Q000378:metabolism*; D007460:Iodoacetamide / Q000008:administration & dosage*; D015289:Leukotrienes / Q000032:analysis; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009195:Peroxidase / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013439:Sulfhydryl Reagents / Q000008:administration & dosage*
D003497:Cyclic N-Oxides; D015289:Leukotrienes; D013113:Spin Labels; D013439:Sulfhydryl Reagents; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; C001803:tempol; D007460:Iodoacetamide