الفهرس 
AIM OF THE WORKOnly 14 pages are availabe for public view
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Abstract
Oral and gastrointestinal mucositis is one of the most common adverse drug reactions of cancer chemotherapy which occurs in about 10–40% of patients receiving cancer chemotherapy. It usually induces severe ulceration and inflammation of the gastrointestinal tract, mainly in the small intestine. The pathophysiology of intestinal mucositis is complex involving several pathogenic elements, including direct toxicity, abnormal inflammation, oxidative stress, and cytokine-induced apoptosis. FU is an anti-metabolite fluorinated pyrimidine anticancer drug that is widely used for the treatment of many tumors. It mainly affects DNA synthesis by competitively inhibiting the TS.
Prevention of mucositis during chemotherapy is always difficult with limited treatment options due to the poorly understood underlying pathobiological mechanisms.(11) One of the proposed drugs for prevention of FU-induced mucositis is statins, with its pleiotropic beneficial effects, including upregulation of endothelial nitric oxide synthase (eNOS) improving endothelial functions, anti-platelet effects, plaque stabilization, macrophage proliferation, anti-inflammatory, anti-oxidant, and immunomodulatory properties.
ROSV is a fully synthetic lipid-lowering agent which is the most potent member of the statins’ family with high effectiveness in cardiovascular risk reduction. Like other family members, it has pleiotropic effects including anti-inflammatory, antioxidant, and anti-thrombotic proprieties with improvement in endothelial functions reducing atherosclerotic lesions. To our knowledge, there are no studies that assessed ROSV as a preventive agent for FU-induced mucositis.
In the present work, we aimed to investigate the possible protective effects of two doses of ROSV, with its pleiotropic effects, to prevent FU-induced intestinal mucositis on a rat model, using several clinical, biochemical, histopathological, and pharmacological assessment methods.
Fifty adult female albino rats weighing 205±21 grams were divided randomly into five groups, and each group consisted of ten rats. The experiment lasted for eight days and was divided into two phases of four days: phase (1) before FU administration and phase (2) after FU administration.
• group 1 (Control group): Rats were administered normal saline (1 ml) daily by oral gavage through an oro-gastric tube. In addition, they received normal saline (0.4 ml) intraperitoneally (i.p.) from day 5 to the end of the experiment.
• group 2 (ROSV group): Rats were administered ROSV with a dose of 20 mg/kg/day by oral gavage through an oro-gastric tube for 8 days.
• group 3 (FU group): Mucositis was induced by administration of FU with a dose of 50 mg/kg/day i.p. for 4 days.
• group 4 (FU+ROSV 10 group): Rats received ROSV with a dose of 10 mg/kg/day by oral gavage through an oro-gastric tube daily for 8 days. FU i.p. (50 mg/kg/day) was added from day 5 to the end of the experiment to induce mucositis.
• group 5 (FU+ROSV 20 group): Rats received ROSV with a dose of 20 mg/kg/day by oral gavage through an oro-gastric tube daily for 8 days. FU i.p. (50 mg/kg/day) was added from day 5 to day 8 to induce mucositis.