Role of prostaglandins in the formation of aspirin-induced gastric ulcers

Lipoxins, The Novel Mediators of Gastroprotection and Gastric Adaptation to Ulcerogenic action of Aspirin

“…In most cases, the reduction of gastric blood flow by itself is not sufficient to produce gastric lesions but it renders the mucosa more susceptible to damage induced by stress, ischemia-reperfusion, corrosive substances (ethanol, 25% NaCl, bile salts) and topically active compounds (ASA) [13]. By blocking the activity of COX-1 by NSAIDs in intact or inflamed gastric tissue, an increase in the gastric acid was observed suggesting that gastric acid plays an important role in the NSAID-induced gastropathy [10,25]. This enhancement in gastric secretion induced by NSAIDs might be more complicated issue, since classic NSAID, indomethacin increased basal but not pentagastrin-stimulated acid secretion in humans while in rats it was capable of increasing both basal-and secretagogue-stimulated gastric acid secretion mainly in inflamed tissue [26,27].…”

“…Epithelial cells is known to trap of charged NSAIDs resulting in enhanced apoptosis subsequent to uncoupling of oxidative phosphorylation. In addition particular lines of gastric defense system including two major ones, namely, mucus and bicarbonate secretion and gastric mucosal blood flow are markedly inhibited [10,13]. This results in decreasing the effectiveness of juxtamucosal pH gradient in protecting gastric epithelium and limits the blood flow to the organ such as stomach rendering it more vulnerable to the damaging action of gastric acid [14].…”

“…This pathogenic action limits the clinical efficacy of ASA known to induce serious side-effects such as induction of acute hemorrhagic erosions, potentiation of gastric ulcerogenic response to various stimuli, exaggeration of colitis and impairment of healing of preexisting ulcers [5][6][7][8]. NSAIDs show even higher rate of gastric damage when concurrently taken with anticoagulants, low dose of ASA taken prophylactically, glucocorticoids or in case of other damaging stimuli such as stress or ischemia-reperfusion or when ASA and other NSAIDs are administered in elderly [9][10][11]. More recently, the ability of NSAIDs to adversely affect renal function has also become recognized.…”

“…Interestingly, topical irritant properties of NSAID do not appear to make a major contribution to their ability to produce acute gastric erosions and chronic ulcerations because untoward effects such as mucosal damage associated with fall in gastroduodenal microcirculation can be observed after the parenteral administration of these drugs [9,10]. One of the most recognized effects of NSAIDs such as ASA on the gastric mucosa is their ability to reduce the mucosal blood flow which functionally belongs to first line of the gastric mucosal defense system [23].…”

“…These approaches have included chiral NSAIDs and enteric coating of the drug to prevent absorption in the stomach, formulation as a pro-drug, to prevent contact between the active drug and the gastric mucosa, and formulation of the drugs for parenteral administration [21]. The basis for each of these approaches was the observation that some NSAIDs, particularly those which are soluble in acidic milieu of the stomach, can directly damage gastric epithelial cells [10]. Suppression of gastric acid appears to be a rationale approach to prevent gastrointestinal damage induced by NSAIDs [22].…”