Oxygen radicals mediate the final exacerbation of endothelin-1-induced gastric ulcer in rat.
We investigated the role of xanthine oxidase-derived oxygen radicals in the development of endothelin-1-induced gastric ulcer. Mucosal lipid peroxidation showed a peak 24 h after injection, while gastric mucosal haemodynamics were fully restored 26 h after endothelin-1 injection. Allopurinol and oxypurinol, but not superoxide dismutase or catalase, protected the gastric mucosa 24 h after endothelin-1 injection. Oxypurinol antagonized both the vasoconstrictor effect of endothelin-1 and the decrease in gastric ATP. All treatments on the second day after endothelin-1 injection significantly reduced gastric mucosal damage. Xanthine oxidase-derived oxygen radicals contributed largely to the exacerbation but they did not mediate the onset of endothelin-1-induced gastric ulcer. Pretreatment with probucol (500 mg/kg, p.o.) also protected the gastric mucosa from endothelin-1-induced mucosal injury by its antioxidant activity. Oxypurinol was gastroprotective through its vasoactive and energy saving actions. The haemodynamic background of endothelin-1-induced gastric ulcer consists of long lasting ischaemia and subsequent "reperfusion" which may be responsible for the late burst of oxygen radicals.
Lazaratos
S
S
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan
Irukayama-Tomobe
Y
Y
Miyauchi
T
T
Goto
K
K
Nakahara
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D018450:Disease Progression; D019332:Endothelin-1 / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010117:Oxypurinol / Q000494:pharmacology; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D011341:Probucol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000447:Aldehydes; D019332:Endothelin-1; D013481:Superoxides; D008315:Malondialdehyde; D000493:Allopurinol; D000255:Adenosine Triphosphate; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D010117:Oxypurinol; D003676:Deferoxamine; C027576:4-hydroxy-2-nonenal; D011341:Probucol