Title: Effect of epidermal growth factor (EGF) and polyamines on the healing of gastric mucosal lesions induced by ischemia-reperfusion
- Michał W. Pawlik, Tomasz Brzozowski, Zbigniew ?liwowski, Stanisław J. Konturek
- Original articles
- Polish Gastroenterology
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- Final page:
- epidermal growth factor, polyamines spermine, ischaemia-reperfusion, ornithine decarboxylase, gastric blood flow, gastric ulcer
The gastric mucosal integrity depends upon the complex interaction between protective and aggressive factors but the mechanisms involved in the maintenance of gastric mucosal integrity and in the healing of gastric mucosal lesions are not completely understood. Polyamines such as spermine or putrescine resul-ting from increased activity of ornithine decarboxylase (ODC) were shown to exhibit gastroprotective and mucosal growth promoting effects but their role in acceleration ofthe healing of ischemia/reperfusion - induced gastric lesions by another potent mitogen such as EGF has been little studied. In this study, two series of Wistar rats (A and B) with ischemia/reperfusion-induced gastric lesions that progressed into the ulcers were used. In series A, the effect of EGF (25 ug/kg s.c, twice daily) and spermine (10 mg/kg-d i.g.), on the time-course of healing of ischemia/reperfusion lesions was determined. In series B, the effect of suppression of ODC activity by an irreversible inhibitor, a-difluoro methylornithine (DFMO 400 mg/kg-d) without or with EGF and spermine was examined. The gastric ischemia/reperfusion lesions were produced in rats by clamping the celiac artery for 0.5 h followed by 3 h of reperfusion and at 0, 3, 12 and 24 h or 3, 5 and 10 daysafterthe end of ischemiaand at each time intervalsthe animals were killed. The area of gastric lesions was determined planimetrically, the gastric blood flow (GBF) was measured by H2-gas clearance. Ischemia alone failed to induce gastric lesions but when it was followed by 3 h of reperfusion, gastric erosive lesions occurredthat were furthersignificantly increasedat 3 h to reach maximumat 12 h butthen progres-sed into ulcers starting from 24 h after ischemia/reperfusion. The GBF was completely inhibited during 30 min of ischemia and significantly reduced after ischemia/reperfusion but then the gradual rise in the GBF starting from 12 h after exposure to ischemia/reperfusion was observed. EGF and spermine significantly accelerated the healing of ischemia/reperfusion lesions progressing to ulcers and this was accompanied by the rise in the GBF. Treatment with DFMO delayed the healing of these lesions and produced a signifi-cant fali in the GBF at each time interval after the end of ischemia/reperfusion. DFMO attenuated significantly the enhancement in ulcer healing and the rise in the GBF evoked by EGF but failed to influence those provoked by exogenous spermine. We conclude that: 1) EGF and polyamines such as spermine accelera-te the healing of ischemia/reperfusion injury due to enhancement in gastric microcirculation; and 2) polyamines may mediate to EGF-induced acceleration of the ulcer healing and improvement of gastric blood flow during mucosal recoveryfrom lesions caused by ischemia/reperfusion.