Protection of cultured rat gastric cells against oxidant stress by iron chelation. Role of lipid peroxidation.
Reactive oxygen metabolites may be involved in the pathogenesis of ethanol-, nonsteroidal antiinflammatory drug-, Helicobacter pylori-, or ischemia/reoxygenation-induced gastric mucosal injury in vivo. Iron plays a critical role in mediating oxidant injury in vitro. The present study examined a possible role of lipid peroxidation in inducing oxidant damage by determining the effect of iron chelation on cytotoxicity and on lipid peroxidation in cultured rat gastric cells. Cytotoxicity was quantified by 51Cr release from prelabeled cells that were exposed to tert-butyl hydroperoxide (tBHP) so as to overwhelm the glutathione redox cycle. Lipid peroxidation was assessed by measuring malondialdehyde (MDA) production. tBHP caused a time-related and dose-dependent increase of 51Cr release. The presence of phenanthroline (a chelator of Fe2+) during tBHP exposure and pretreatment with deferoxamine (a chelator of Fe3+) reduced tBHP-induced 51Cr release dose dependently. The generation of MDA increased as the concentrations of tBHP increased, but in a time course study, such generation preceded cytolysis. Both iron chelators attenuated MDA production in a dose-dependent fashion. Oxidant stress causes lipid peroxidation in cultured gastric cells, which is then followed by cytolysis. Iron plays a critical role in inducing lipid peroxidation as well as in mediating cytolysis. Iron chelation protects these cells from oxidant stress presumably through inhibition of lipid peroxidation.
Yajima
N
N
Second Department of Internal Medicine, Dokkyo University School of Medicine, Tochigi, Japan.
Hiraishi
H
H
Harada
T
T
D000818:Animals; D002478:Cells, Cultured; D002860:Chromium Radioisotopes; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D010545:Peroxides / Q000494:pharmacology; D010618:Phenanthrolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020122:tert-Butylhydroperoxide
D002860:Chromium Radioisotopes; D007502:Iron Chelating Agents; D010545:Peroxides; D010618:Phenanthrolines; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D020122:tert-Butylhydroperoxide; D003676:Deferoxamine; C025205:1,10-phenanthroline