Influence of Cyclodextrin Complexation with NSAIDs on NSAID/Cold Stress-Induced Gastric Ulceration in Rats
نویسندگان
چکیده
The aim of this work was to study the ability of beta-cyclodextrin (beta-CD) or hydroxypropyl beta-cyclodextrin (HP-beta-CD) to ameliorate the induction of gastric ulcers by a nonsteroidal anti-inflammatory drug, indomethacin or piroxicam, in rats exposed to restraint and hypothermic stress at 4 degrees C. Using oral gavage, rats fasted for 72 h were administered the equivalent of a 100 mg/kg dose of the assigned drug, alone or with the designated cyclodextrin (CD). The rats were placed in suitable rodent restrainers and then placed inside a ventilated refrigerator maintained at a temperature of 4 degrees C. Six hours later, each animal was removed, anaesthetized with ether, and the abdomen opened. Each stomach was removed, opened along the greater curvature and gently rinsed with isotonic saline solution. The induced gastric ulcers were examined and assessed with the help of a 10x binocular magnifier. Pronounced and marked gastric ulceration with complete loss of the mucosa, extensive deposition of fibrin and dense neutrophilic infiltrate were observed in rats treated with each of the drugs alone. Treatment with indomethacin or piroxicam alone induced ulcer indices of 26 +/- 2.3 or 14 +/- 1.8, respectively. However, beta-CD and HP-beta-CD each significantly suppressed ulceration due to restraint and cold stress. Rats treated with indomethacin or piroxicam in the presence of either beta-CD or HP-beta-CD exhibited normal tissues. Therefore, beta-CD and HP-beta-CD act as protective agents against gastrointestinal disorders produced by restraint and cold stress, even with the added stress from administration of either indomethacin or piroxicam.
منابع مشابه
Gastroprotective role of bioflavonoid silymarin in animal model of acute cold-restraint stress induced gastric ulceration
Introduction: Imbalance between the aggressive and defensive factors and presence of acidpepsin is supposed to play a major role in aetiopathogenesis of peptic ulcer disease. Recently, role of oxidative free radicals have been implicated in mediating cold-restraint stress, H.pylori, NSAID induced gastric injury. Objective: The present study was undertaken to evaluate the possible role of antiox...
متن کاملHydroxyproline, a Serum Biomarker Candidate for Gastric Ulcer in Rats: A Comparison Study of Metabolic Analysis of Gastric Ulcer Models Induced by Ethanol, Stress, and Aspirin
Gastrointestinal symptoms are a common manifestation of adverse drug effects. Non-steroid anti-inflammatory drugs (NSAIDs) are widely prescribed drugs that induce the serious side effect of gastric mucosal ulceration. Biomarkers for these side effects have not been identified and ulcers are now only detectable by endoscopy. We previously identified five metabolites as biomarker candidates for N...
متن کاملDiazoxide, a KATP Channel Opener, Prevented Ethanol-Induced Gastric Ulceration in Rats
Ethanol-induced acute gastric ulceration (EIGU) is widely studied. ATP dependent potassium channel (KATP) modulators are thought to interfere with some physiologic functions of the stomach. We have studied the effects of different doses of KATP modulators (diazoxide as agonist and glibenclamide as antagonist) on EIGU in rats. Gastric lesions were quantified. Fasting blood glucose (FBS) levels w...
متن کاملThe Protective Effect of Nortriptyline Against Gastric Lesions Induced by Indomethacin and Cold-shock Stress in Rats
Background: Gastric ulcer is among the most serious stomach disorder universally. Several effective drugs are employed in the management of this disease, although there have been adverse effects in some cases. The aim of this study was to investigate the effect of nortriptyline to protect against gastric lesions, induced by indomethacin or cold-stress in rats. Methods: Gastric lesions were ind...
متن کاملHow do NSAIDs cause ulcer disease?
Gastroduodenal ulceration and bleeding are the major limitations to the use of non-steroidal anti-inflammatory drugs (NSAIDs). The development of safer NSAIDs or of effective therapies for the prevention of the adverse effects of existing NSAIDs requires a better understanding of the pathogenesis of NSAID-induced ulcer disease. NSAIDs can cause damage to the gastroduodenal mucosa via several me...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 7 شماره
صفحات -
تاریخ انتشار 2010