TEMPOL, a membrane-permeable radical scavenger, attenuates gastric mucosal damage induced by ischemia/reperfusion: a key role for superoxide anion.
The pathogenesis of gastric mucosal injury is a multifaceted process involving reactive oxygen and nitrogen species, both of which play a crucial role in the ischemia/reperfusion model of gastric damage. Hence, several studies have evaluated the anti-ulcerogenic effect of metal chelators, antioxidative enzymes, and low-molecular-weight antioxidants. Low molecular weight superoxide dismutase (SOD) mimetics have been shown to play a protective role against oxidative damage. Therefore, the aim of the current study was to investigate the modulatory effect of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl [TEMPOL (50 mg/kg)], a SOD mimetic, and the SOD inhibitor, diethyldithiocarbamate [DETCA (100 mg/kg)] on gastric lesions induced by ischemia/reperfusion. This insult produced typical gastric lesions, a significant fall in the gastric mucosal glutathione (GSH) and nitric oxide (NO) levels, accompanied by an increase in malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. TEMPOL markedly minimized gastric ulceration and restored MDA, NO, and MPO levels, but did not alter GSH level, which dropped drastically in DETCA treated group, an effect that was not reflected on gross lesions induced by ischemia/reperfusion. In conclusion, TEMPOL can confer protection from gastric ischemia/reperfusion injury possibly by reducing the level of superoxide anion (O(2)(*-)), replenishing NO, and minimizing neutrophil infiltration. Therefore, specific SOD mimetics could be beneficial as complementary agents in the management of gastric ulceration.
Abdallah
Dalaal M
DM
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Mohamed.alaa@bms.com
El-Abhar
Hanan S
HS
Abdel-Aziz
Dalia H
DH
D000818:Animals; D002463:Cell Membrane Permeability; D003497:Cyclic N-Oxides / Q000378:metabolism* / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000378:metabolism / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D013113:Spin Labels; D013481:Superoxides; D004958:Estradiol; C073106:3,17-diacetoxyestra-1,3,5(10)-trien-2-carboxylic acid; D009195:Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; C001803:tempol