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Abstract

The aim of the present work was to study in vivo COX-2-COX-1 selectivity of 16 nonsteroidal anti-inflammatory drugs (NSAIDs) in equipotent ulcerogenic doses in two in vivo experimental models. Indomethacin, ibuprofen, nimesulide, aceclofenac, aspirin, sodium diclofenac, meloxicam, naproxene, paracetamol, piroxicam, tenoxicam, nabumetone, ketoprofen, mefenamic acid, etodolac, and ketorolac were administered to female Wistar rats (N = 10 each group). In experiment I, solid food plus subcutaneous NSAIDs were given. In experiment II, NSAIDs were given by oral gavage and in bolus. Macroscopic gastric antral ulcer area (30%) and intestinal erosiva area (295 mm2) in experiment I and necrotic gastric fundus area (65%) and erosive intestinal area (182 mm2), "in vivo" the NSAIDs COX-1 was showed. Neutrofilia assessed in gastric intestinal mucosa where also ibuprofen and paracetamol not given neotrophilic infiltration. In conclusion, COX-2-COX-1 selectivity was demonstrated in vivo with the drugs aceclofenac, nabumetone, meloxicam, nimesulide, and paracetamol.

Ketogal Safety Profile in Human Primary Colonic Epithelial Cells and in Mice

“…Once it was established that ketogal did not induce oxidative stress in the lower GI tract, consistent with most clinical studies of NSAIDs, we demonstrated the safer profile of ketogal compared with ketorolac in the other organs as well, particularly in the upper GI tract [3,7] and in the liver [16,17]. Consistently, we examined histopathological changes after repeated oral treatment in mice with ketorolac and ketogal, under the conditions previously adopted for the stomach and kidneys in our past work [31].…”

“…It is known that long-term use of NSAIDs can damage the small and large intestines in healthy subjects, causing bleeding and perforation, erosion, ulcers, and bowel obstruction [7,8]. This can lead to reduced intestinal absorption capacity and increased permeability [9,10].…”

Effect of psychogenic stress on gastrointestinal function

“…However, serum levels are unchanged (40). Somatostatin exerts a weak protective effect on gastric damage, but only at low doses (68, 99,210). The mechanism has been attributed to decreased acid secretion (194) or antioxidative actions (110).…”

“…It does not influence neutrophilic infiltration or transmucosal fluid flux (29). An analysis of the data from several studies shows a significant correlation between constirutive NO synthase (eNOS) activity, inhibition of neutrophil infiltration, and mucus production (131,132), while inducible NO synthase (iNOS) is clearly detrimental (95,101,130). Further, two groups have independently demonstrated that eNOS is reduced and iNOS is induced in stress (131,132,185).…”

Synthesis and Evaluation of Antioxidant, Anti-inflammatory and Antiulcer Activity of Conjugates of Amino Acids with Nifedipine

“…[1][2][3] The role of free radicals in inflammation of gastric mucosa and use of antioxidants for protection against ulceration has been widely suggested. 4,5) Several amino acids 6) and their conjugates with curcumin, 7) pyrrole 8) and 5H-dibenzazepine 9) have been reported with significant antioxidant action. Inspired with antisecretory profiles of nifedipine and antioxidant properties of amino acids and in connection with our research on the design and synthesis of biologically active and pharmacologically important new heterocycles, it was thought worthwhile to synthesize the amino acid conjugates of nifedipine with a view to obtain certain new chemical entities with potential to reduce excess gastric acid secretion as well as protect gastric mucosa against inflammation and ulceration.…”