الفهرس 
Introduction
Chapter 1: Etiology and experimental induction of gastric ulcersOnly 14 pages are availabe for public view
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Abstract
The present study was conducted to investigate the different therapeutic effects of omeprazole, melatonin and melatonin loaded-niosomes on ethanol induced gastric lesions by studying the gross, microscopic and biochemical changes associated with each drug.
To fulfill our goals, ninety five female albino rats were used for this study. The rats were apparently healthy, weighting about 200-250gms and randomly assigned to five groups according to the experimental design.
In the first group (induction group), 10 rats were given 1ml of ethanol (70%) and sacrificed after 1 hour. The effect of ethanol was assessed grossly, histopathologically and biochemically. Gastric mucosa was examined grossly for the presence of various lesions and were scored. The ulcer index for this group was calculated. Samples form prominent gastric lesions were preserved in neutral buffered formaline for histopathological examination and in the ice-cold 0.9% saline (pH 7.0) for biochemical analysis of tissue homogenate of LP and TA.
The gross findings were expressed by the presence of frank ulcers and necrotic masses in addition to hyperemia and hemorrhages. The histopathological results revealed the presence of mucosal ulcerative lesions which demonstrated by diffuse coagulative hemorrhagic necrosis and focal deep ulcers affecting almost the whole thickness of the mucosal layer, in addition to submucosal and serosal angiopathic changes represented by oedema, hyperemia, endothelial damage and vacuolation of tunica media as well as heavy inflammatory cellular infiltration. The observed changes were attributed to the direct effect of ethanol on the gastric mucosa and the angiopathic effect of ethanol on the gastric vasculature.
The biochemical results revealed extremely significant decrease in tissue homogenate level of LP and extremely significant increase in tissue homogenate TA level. These results proved that ethanol administration promoted oxidative stress and development of ROS.
In the second group (omeprazole-treated group), 25 rats were administrated 4mg/rat omeprazole daily by oral intubation after successful induction of ulcer by ethanol. Five rats were sacrificed after 3,7.14,21,28 days post-treatment. Gross lesions were assessed and ulcer index were calculated for each subgroup. Also the histopathological examinations of the selected lesions and biochemical analysis of tissue homogenates were performed.
Gross findings revealed hemorrhagic ulceration of gastric mucosa at 3 and 7 days post omeprazole treatment with ulcer index 2.6,1.8 respectively. After 14 and 21 days post treatment, gastric mucosa showed diffuse superficial necrosis with ulcer index 1.6 for both subgroups. In the last subgroup, gastric mucosa showed only foci of superficial necrosis with ulcer index 0.8.
Histopathologically, gastric mucosa showed frank ulcers at 3 days post omeprazole therapy. Evidence of regenerating ulcer with granulation tissue formation and neoangiogenesis was seen at 7 days post-treatment. The necrosis and desquamation of mucosal epithelium became of lesser intensity and severity after 28 days post-treatment. The vascular damage was obvious at 3 days and persisted till the end of the experiment but of lesser intensity and severity especially at 21 and 28 days post-treatment. The inflammatory cellular infiltration was not significantly affected by omeprazole therapy.
Biochemically, there was a significant decrease in tissue homogenate LP and significant increase in tissue homogenate TA levels after 14 days of treatment. The effect of omeprazole was due to its antisecretory and antioxidant effect which helped in healing of ulcer.
In the third group (melatonin-treated group), 25 rats were administrated 2mg/rat melatonin by gastric tube daily after induction of ulcer by ethanol. Five rats were sacrificed after 3,7.14,21,28 days post-treatment. Gross lesions were carried out and ulcer index were calculated for each subgroup as well as histopathological examinations and biochemical analysis of tissue homogenate were performed.
Gross results revealed the presence of large necrotic masses and longitudinal ulcerative lesions at 3 and 7 days post-treatment with ulcer index 2.8,1.2 respectively, while after 14 and 21 days, the gastric mucosa showed only tiny superficial necrosis with ulcer index 0.8 and 0.6 respectively. Rats which sacrificed at the end of the experiment showed intact gastric mucosa without any gross lesions.
Histopathologically, ulcerative lesions were observed at 3 and 7 days post-treatment with early granulation and angiogenesis at ulcer base. After 14 days post-treatment, gastric mucosal changes gradually reduced till completely disappeared after 28 days. The angiopathic changes gradually improved till completely disappeared after 21 days post melatonin therapy. Also inflammatory cellular infiltration was significantly reduced particularly after 14 days post-treatment.
The biochemical results showed that melatonin caused extremely significant decrease in LP and extremely significant increase in TA tissue homogenate levels. The gastroprotective effect of melatonin was due to its potent antioxidative effect.
The fourth group (melatonin-loaded niosomes treated group) consisted of 25 rats which were given melatonin-loaded niosomes in the same dose and route as the third group. Five rats were sacrificed after 3,7.14,21,28 days post-treatment representing different subgroups. Gross lesions were recorded and ulcer index were calculated for each subgroup as well as histopathological examinations and biochemical analysis of tissue homogenate were performed to determine LP and TA levels.
Gross findings revealed the presence of necrotic mass in one rat while the rest showed only superficial erosions with ulcer index 1.4after 3 days post-treatment. After 7 days, two rats showed pinpoint superficial necrosis while others showed intact gastric mucosae with ulcer index 0.8. Rats which were sacrificed at 14, 21 and 28 days post-treatment didn’t show any gross lesions.
Histopathologically, after 3 days post-treatment only one rat showed coagulative necrosis of the gastric mucosa while the others showed only superficial necrosis and desquamation while after 7 days, the mucosal lesions included focal areas of necrosis and desquamation in only two rats while other rats showed superficial sloughed epithelium. Rats examined at 14. 21 days post–treatment showed minute sloughed epithelium and at the end of study, the gastric mucosa showed intact epithelium. The angiopathic changes gradually improved till completely disappeared after 14 days post melatonin-loaded niosomes therapy. In addition, the inflammatory cellular infiltration was markedly improved after 7 days post-treatment.
The biochemical results supported the forementioned findings and revealed that melatonin loaded niosomes-treated group showed extremely significant decrease in LP and extremely significant increase in TA in all its subgroups. This is due to the high accumulative effect of the drug in the targeted tissue and due to the ability of niosomes to improve the therapeutic efficacy of melatonin against oxidative damage in gastric tissue.