TY - JOUR
T1 - Gastric injury induced by ethanol and Ischemia-Reperfusion in the rat
T2 - Differing roles for lipid peroxidation and oxygen radicals
AU - Smith, Gregory S.
AU - Mercer, David W.
AU - Cross, James M.
AU - Barreto, Jose C.
AU - Miller, Thomas A.
PY - 1996
Y1 - 1996
N2 - This study determined the role that oxygen-derived free radicals played in the production of gastric injury in rats challenged orally with concentrated ethanol or subjected to vascular compromise. In the ethanol study, rats were pretreated with a variety of free radical scavengers or enzyme inhibitors prior to exposing the stomach to 100% ethanol. At sacrifice, the degree of macroscopic damage to the glandular gastric mucosa was quantified. In separate studies, the effects of ethanol on gastric mucosal levels of enaldehydes (malondialdehyde and 4-hydroxynonenal) were examined as an index of lipid peroxidation. Superoxide dismutase and catalase pretreatment were without benefit in reducing injury in our ethanol model, excluding potential contributory roles for the superoxide anion or hydrogen peroxide, respectively. Dimethyl sulfoxide and desferoxamine were likewise without protective capabilities, eliminating a role for the hydroxyl radical. Allopurinol, a xanthine oxidase inhibitor, provided no protection under-acute conditions, even though partial protection was noted when administered chronically. Further, enaldehyde levels were not increased over control levels in alcohol-exposed mucosa, indicating no enhanced lipid peroxide formation. In contrast, in animals in which ischemia to the stomach was induced followed by reperfusion, marked gastric injury was observed in combination with enhanced enaldehyde levels. Prevention of enaldehyde formation by a 21-aminosteroid concomitantly prevented injury induced by ischemia-reperfusion. These findings support the conclusion that ischemia-reperfusion injury to the stomach is an oxygen-derived free radical process whereas ethanol-induced injury clearly involved some other process. Although allopurinol was partially protective against ethanol damage when administered chronically, observations in other models of injury suggest that this action is independent of its inhibitory effect on xanthine oxidase.
AB - This study determined the role that oxygen-derived free radicals played in the production of gastric injury in rats challenged orally with concentrated ethanol or subjected to vascular compromise. In the ethanol study, rats were pretreated with a variety of free radical scavengers or enzyme inhibitors prior to exposing the stomach to 100% ethanol. At sacrifice, the degree of macroscopic damage to the glandular gastric mucosa was quantified. In separate studies, the effects of ethanol on gastric mucosal levels of enaldehydes (malondialdehyde and 4-hydroxynonenal) were examined as an index of lipid peroxidation. Superoxide dismutase and catalase pretreatment were without benefit in reducing injury in our ethanol model, excluding potential contributory roles for the superoxide anion or hydrogen peroxide, respectively. Dimethyl sulfoxide and desferoxamine were likewise without protective capabilities, eliminating a role for the hydroxyl radical. Allopurinol, a xanthine oxidase inhibitor, provided no protection under-acute conditions, even though partial protection was noted when administered chronically. Further, enaldehyde levels were not increased over control levels in alcohol-exposed mucosa, indicating no enhanced lipid peroxide formation. In contrast, in animals in which ischemia to the stomach was induced followed by reperfusion, marked gastric injury was observed in combination with enhanced enaldehyde levels. Prevention of enaldehyde formation by a 21-aminosteroid concomitantly prevented injury induced by ischemia-reperfusion. These findings support the conclusion that ischemia-reperfusion injury to the stomach is an oxygen-derived free radical process whereas ethanol-induced injury clearly involved some other process. Although allopurinol was partially protective against ethanol damage when administered chronically, observations in other models of injury suggest that this action is independent of its inhibitory effect on xanthine oxidase.
KW - Ethanol
KW - Gastric injury
KW - Ischemia-reperfusion
KW - Lipid peroxidation
KW - Oxygen-derived free radicals
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U2 - 10.1007/BF02088232
DO - 10.1007/BF02088232
M3 - Article
C2 - 8654147
AN - SCOPUS:0030013211
SN - 0163-2116
VL - 41
SP - 1157
EP - 1164
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 6
ER -