Anti-ulcerative, Anti-oxidative, and Anti-inflammatory Effects of Rosuvastatin and Isosorbide Dinitrate on Cysteamine-Induced Chronic Duodenal Ulcer in Rats

Although many drugs are available for treatment of duodenal ulcer (DU), there is a growing concern in alternative therapies with reduced adverse effects in refractory patients. Oxidative stress, decreased generation and bioavailability of nitric oxide (NO), and various inflammatory pathways are widely implicated in the pathogenesis of DU. Statins display different gastroprotective effects through their antioxidant and anti-inflammatory roles with less well studied anti-ulcerative effects on DU diseases. Accordingly, this study was evaluated the possible anti-ulcerative effects of rosuvastatin and isosorbid dinitrate (ISDN) each alone and in combination versus omeprazole on cysteamine-induced chronic DU in rats. Cysteamine-HCl induced chronic DU models were done in 72 adult male albino Wistar rats. Rosuvastatin (20 mg/kg), ISDN (5 mg/kg), and omeprazole (20 mg/kg) were given orally. The anti-ulcerative activities were assessed through measuring the ulcer area, ulcer histopathological score, ulcer index, duodenal NO, tumor necrosis factors-α (TNF-α), interleukin (IL)-1β, malondialdehyde (MDA), and reduced glutathione (GSH) levels and duodenal superoxide dismutase (SOD) and catalase (CAT) activities. Rosuvastatin and/or ISDN significantly improved cysteamine-induced DU as evidenced by significant decreases in ulcer index, lipid peroxidation, TNF-α, and IL-1β levels, and increase in NO and GSH levels as well as increased antioxidant enzymes activities; SOD and CAT. Moreover, the combined treatment showed better results compared to rosuvastatin or omeprazole monotherapies. Finally, rosuvastatin and ISDN have anti-ulcerative, antioxidant and anti-inflammatory activities against cysteamine-induced DU in rats. Combined treatment is advantageous. Further studies for the combined-long term effects should be done especially in cases with co-morbidity