الفهرس 
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Abstract
The present investigation was an attempt to study the effects of pretreatment with aspirin (as an example of non-selective COX-inhibitor) and rofecoxib (as an example of selective COX-2 inhibitors) as well as nitric oxide releasing aspirin on cold-restraint stress-induced ulcer model. Also, the effects of oral and intraperitoneal administration of sodium salicylate were investigated. In addition, the possible involvement of some chemical mediators, namely, lipid peroxides, nitric oxide and prostaglandin E2 as targets for the ulcer-protective action of those agents, were investigated.
In the present study, male albino rats weighing 150-250 gm were fasted for 24 hours prior to experimentation. Pyloric ligation was performed under light ether anesthesia before induction of ulcer by cold restraint stress. After pyloric ligation, the animals were restrained by fixing the four limbs to a wooden board and they were placed in a refrigerator at 4 °c for 3 hours. The study involved the following experimental groups: Control (non-stressed) group; in which animals were left freely wandering in their cages for 3 hours after being subjected to pyloric ligation, cold-restraint-stressed group; in which rats received carboxymethylcellulose only, aspirin-pretreated group (30 mg/kg; oral), rofecoxib-pretreated group (5 mg/kg; oral), nitric oxide releasingpretreated group (55 mg/kg; oral), oral sodium salicylate-pretreated group (50 mg/kg) and intraperitoneal sodium salicylate-pretreated group (50 mg/kg). All the drugs were given in 1 % carboxymethylcellulose thirty minutes prior to initiation of cold-restraint stress.
After completion of the 3 hours of stress, rats were sacrificed using an overdose of ether. Their stomachs were removed and opened along the
greater curvature and gastric content of each stomach was collected for analysis of gastric juice volume, pH, total and free acid concentrations and outputs, mucin and pepsin concentration and output concentration.
The stomachs were washed with ice-cold saline and scored for gross mucosal lesions, washed with indomethacin (1 O~g/ml) and immediately stored at -80Ge for assessment of mucosal content of lipid peroxide, nitric oxide and PGE2. A representative stomach from each group was immersed in 10% formalin for histopathologic examination.
q Ulcerative lesions were observed in cold restraint stressed rats; the ulcer index mounted to 5.50 ± 0.67.
q Pretreatment of cold restraint stressed rats with aspirin, in a dose of 30 mg/kg, significantly increased the severity of mucosal lesions with an ulcer index reaching 7.83 ± 0.17. The aspirin pretreated group showed increased volume of gastric juice, pepsin concentration and output, and pH while lowering free and total acid concentrations and outputs and gastric juice mucin concentration. Pretreatment with aspirin caused a significant elevation in the level of mucosal lipid peroxidation as well as mucosal total nitrites with a reduction in mucosal PGE2 level.
q Pretreatment of cold restraint stressed rats with rofecoxib (5mg/Kg), in a dose of 30 mg/kg, did not increase mucosal ulcerogenic response induced by hypothermic stress. It, in the contrary, reduced the stresssinduced ulcer fOffi1ation achieving an ulcer index of 2.17 ± 0.40 and a preventive index of 62%. Rofecoxib showed lower gastric juice volume free and total acid concentrations and outputs and pepsin
.