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dc.contributor.authorONWUCHEKWA, CHINEDU-
dc.date.accessioned2019-03-25T16:01:33Z-
dc.date.available2019-03-25T16:01:33Z-
dc.date.issued2015-02-
dc.identifier.urihttp://adhlui.com.ui.edu.ng/jspui/handle/123456789/864-
dc.descriptionA Thesis in the Department of Physiology submitted to the Faculty of Basic Medical Sciences, College of Medicine, in partial fulfillment of the requirements for the award of the Degree of Doctor of Philosophy of the University of Ibadan, Nigeria.en_US
dc.description.abstractGastric ulcer and its treatment is a global problem, thus the search for a novel drug becomes a continuous one. Risperidone, though, anti-psychotic has been found to exhibit anti-ulcer activity, however, its mechanisms of action are yet to be fully elucidated. The study was designed to investigate the mechanisms underlying its anti-ulcer activity in rats. Three hundred and thirty-six male Wistar rats (180-210 g) were divided into 5 groups of 96, 48, 96, 64 and 32 rats respectively and treated orally for 21 days. Ninety-six of them were divided into 3 sub-groups to be induced with ulcer using indomethacin, starvation and Water Immersion Restraint Stress (WIRS) methods. Each sub-group was pre-treated with distilled water (control) and risperidone (0.1, 0.3, 0.5 mg/kg). Forty-eight rats were further divided Into 6 groups; risperidone (0.5 mg/kg), indomethacin (40mg/kg), cyclooxygenase-1 inhibitor (SC-560, 40mg/kg), cyclooxygenase-2 inhibitor (celecoxib, 15 mg/kg), celecoxib + SC-560 and celecoxib + SC-560 risperidone. Gastric ulcers were scored using standard techniques. Ninety-six rats were divided into 3 sub-groups, with each group treated with distilled water and risperidone (1.1, 0.3, 0.5 mg/kg) and were assessed for Gastric Acid Secretion (GAS) induced by histamine, pentagastrin and carbachol using continuous perfusion techniques. Sixty-four rats were divided into 2 sub-groups and treated with distilled water and risperidone (0.1, 0.3, 0.5 mg/kg) for the assessment of Gastric Mucus Secretion (GMS) and Gastric Mucus Cell Counts (GMCC) using spectrophotometry and calibrated microscopy respectively. Thirty two rats divided into four treatment groups; distilled water and risperidone (0.1, 0.3, 0.5 mg/kg) were used for determination of malondialdehyde level by spectrophotometry. Histological studies on stomach tissues were done after staining with H&E and PAS stains using light microscope. Data were analysed using Student's t-test and ANOVA at p= 0.05. Risperidone caused a significant dose-dependent reduction in gastric ulcer scores [0.1mg/kg (3.5±4.2), 0.3mg/kg (1.9±0.3), 0.5mg/kg (1.2±0.2)] compared with control (5.6±0.3) in WIRS., [0.1 mg/kg (4.0 ±0.3), 0.3mg/kg (2.3±0.2), 0.5mg/kg (1.8.±0.2)] compared with control (6.1 ± 0.3) in starvation and [0.1 mg/kg (4.9±0.3), 0.3 mg/kg (2.0±0.2), 0.5 mg/kg (1.3±0.2)] compared with control (6.4±0.4) in indomethacin-induced ulcer models. Celecoxib in combination with SC-560 caused significant gastric damage with gastric ulcer score of 4.3±0.4, which was significantly reduced by risperidone (0.5 mg/kg; 1.6±0.2). Risperidone significantly inhibited GAS induced by histamine and pentagastrin but not GAS produced by carbachol. The GMS (mg/g tissue 10⁻²) increased significantly in the 0.1 mg/kg (1.1±0.1), 0.3mg/kg (1.3±0.1) and 0.5mg/kg (1.4±0.2) compared with the control (0.6±0.03). There was a dose-dependent increase in the GMCC (mm²) in risperidone-treated groups [0.1 mg/kg, 121.2±5.0), 0.3mg/kg (129±2.5) and 0.5mg/kg (129±3.8)] relative to the control (103.3±4.2). Malondialdehyde (nmonl/L 10⁹) level was significantly decreased by risperidone [0.1mg/kg (194.0±0.01), 0.3mg/kg (183.0± 0.01) and 0.5mg/kg (106.0± 0.01) compared to control group (257.0± 0.01). Histology revealed reduced mucosal epithelial and lamina propria damage in risperidone-treated groups compared with control. Risperidone reduced gastric ulceration via mechanisms related to inhibition of gastric acid secretion mediated through histamine H₂ and gastrin receptors. Its anti-ulcer property may also be related to its antioxidant, gastroprotective and cyclooxygenase modulating activities.en_US
dc.language.isoenen_US
dc.subjectRisperidoneen_US
dc.subjectStarvation-induced gastric ulceren_US
dc.subjectGastroprotectionen_US
dc.subjectCyclooxygenase modulationen_US
dc.titleMECHANISMS OF THE ANTI-GASTRIC ULCER ACTIVITY OF RISPERIDONE IN MALE RATSen_US
dc.typeThesisen_US
Appears in Collections:Theses in Physiology

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