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Title: Studies on the therapeutic potential of amoxycillin on acetic acid–induced colitis in rats
Authors: Al Shehri, Abdullah Sahib Saeed
Keywords: Pharmacology
Acetic acid–induced colitis
Ulcerative colitis
Chronic inflammatory disease
Biochemical parameters
تاريخ النشر: 2006
Abstract: Ulcerative Colitis is a chronic inflammatory disease characterized by an acute phase of inflammation of the colonic mucosa with inflammatory changes followed by an inactive and quiescent periods. The mechanism of tissue damage in Ulcerative Colitis is unknown. However, recent evidence suggests that the reactive oxygen species are critical mediator of inflammation and tissue damage in ulcerative colitis. Various experimental models of colitis mimicking the acute phase of the disease have been developed to test the potential therapeutic effects of various drugs. Therefore, the present study was designed to investigate the probable beneficial effects and to elucidate the mechanism of action of amoxycillin, a potential antioxidant, on acetic acid-induced colitis in rats. Acetic acid-induced colitis was produced in rats and assessment of macroscopic lesions was performed by the modification of the method described by Millar et al., 1996. Haematoxylin and eosin staining performed the histopathological evaluation. Biochemical parameters such as reduced glutathione levels, myeloperoxidase activity and extravasations of Evans blue (vascular permeability) were measured following standard assay procedures. Characteristic acute colonic lesions were developed 24 h after intra rectal administration of 3% acetic acid . These lesions were associated with depletion of reduced glutathione, increased in both myeloperoxidase activity and extravasations of Evans blue (vascular permeability). Furthermore, microscopically there were loss of epithelial cells, submucosal oedema, haemorrhage and increased infiltration of inflammatory cells in the mucosa. These acute lesions along with associated changes in biochemical parameters and microscopic findings were altered gradually with time but still very much evident on day 6 following acetic-acid induced colitis. Administration of twice daily doses of amoxycillin (25, 50 and 100 mg / kg ) orally or rectally 48, 24 or 2 hr before induction or for five consecutive days starting 6 h after induction of colitis by acetic acid, dose dependently inhibited colonic lesions. Furthermore, the biochemical and histological changes were reversed and brought towards the control levels by both regimes. On the other hand, administration of a fixed dose (400 mg / kg) of sulphasalazine following similar protocols as described above also reduced the severity of colitis and reversed the biochemical and microscopic changes caused by acetic acid. No significant difference was found between the values obtained at each dose level after oral or rectal administration of amoxycillin or sulphasalazine. The results of this study suggest that the mechanisms of the beneficial effects of amoxycillin against acetic acid-induced colitis may include prevention of depletion of reduced glutathione, reduction of myeloperoxidase activity, decreased vascular permeability and inhibition of infiltration of inflammatory cells in the mucosa. These findings indicate that the effectiveness of amoxycillin may be partly due to its antioxidant property. Further experimental and clinical investigations are warranted to determine its therapeutic potential and mechanism (s) of action in ulcerative colitis.
Description: This study has been conducted & Submitted in partial fulfillment of the requirements for the Master’s Degree in Pharmacology at the Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia, 1427H – 2006G
URI: http://hdl.handle.net/123456789/8834
يظهر في المجموعات:College of Medicine

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