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1 Journal of Physiology and Pharmacology

1 2002

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Effects of reactive oxygen species action on gastric mucosa in various models of mucosal injury

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Kwiecien S. , Brzozowski T. , Konturek S. J.

nr 1

The exposure of gastric mucosa to damaging factors,such as ethanol,water restraint stress,or ischemia followed by reperfusion,produces pathological changes: inflammatory process,hemorrhagic erosions,even acute ulcers.The base of these changes is a disturbance of protective mechanisms and disrupture of gastric mucosal barrier.Previous studies pointed out the role of disturbances of gastric blood flow,mucus secretion and involvement of prostaglandins and nitric oxide formation in the pathomechanism of gastric mucosa lesions.The role of reactive oxygen species (ROS)in these processes has been little studied.Aim:The purpose of our present investigations is to explain the participation of ROS in acute gastric mucosal damage by various irritants.Material and methods:Experiments were carrying out on 80 male Wistar rats.To assess gastric blood flow (GBF)laser Doppler flowmeter was used.The area of gastric lesions was established by planimetry.The levels of proinflammatory cytokines were measured by ELISA technique.The colorimetric assays were used to determine of malondialdehyde (MDA)and 4-hydroxynonenal (4-HNE)as well as superoxide dismutase (SOD)activity.Results:We demonstrated that 3.5 h of water immersion and restraint stress (WRS),30 min of gastric ischemia followed by 60 min of reperfusion or intragastric administration of 100%ethanol,all resulted in appearance of acute gastric mucosal lesions accompanied by a significant decrease of gastric blood flow. These lesions are also accompanied by the significant increase of proinflammatory cytokines including interleukin –1 beta (IL-1 ß )and tumor necrosis factor alpha (TNF alpha )plasma level. Biological effects of ROS were estimated by measuring tissue level of MDA and 4-HNE, the products of lipid peroxydation by ROS,as well as the activity of SOD,the scavanger of ROS.It was established that 3.5 h of WRS,ischemia-reperfusion and 100%ethanol lead to significant increase of MDA and 4-HNE mucosal level,accompanied by a decrease of SOD activity (significant in WRS and ethanol application).Conclusions:The pathogenesis of experimental mucosal damage in rat stomach includes the generation of ROS that seem to play an important role,namely due to generation of lipid peroxides,accompanied by impairment of antioxidative enzyme activity of cells.