Pathogenesis of Gastric Lesions Induced by Aspirin in the Pylorus-Ligated Rat

Abstract

Abstract-A standard method for the production of gastric lesions by aspirin in rats was elaborated, and the mechanisms of the deleterious effects of aspirin were inter preted. The method consisted of pylorus ligation of the rat immediately before as pirin dosing, resulting in severe and consistent gastric lesions in the glandular por tion of the rat stomach 7 hr later. Sodium bicarbonate and L-glutamine showed a strong inhibitory effect on the development of aspirin-induced lesions, at almost the same dose level. Aspirin itself reduced the gastric acidity in pylorus-ligated rats. Sodium bicarbonate with or without aspirin markedly lowered the gastric acidity, whereas L-glutamine with or without aspirin restored the reduced acidity by aspirin or increased the acidity more than the normal level. These findings suggest that L glutamine may inhibit the back diffusion of HCl into the gastric mucosa caused by aspirin. Amylopectine sulfate and sulfated glyptide, in a dose sufficient to suppress the peptic activity of gastric contents, slightly inhibited the aspirin-induced lesions. Atropine sulfate, which strongly reduced gastric juice volume but not acidity, did not exert a marked influence on aspirin-induced lesions.It is well known that aspirin is capable of damaging the gastric mucosa in humans and experimental animals, and that this can be detected by a variety of techniques (1, 2). In animals, however, the incidence and severity of gastric lesions induced by aspirin was re portedly rather weak at the time of autopsy. This fact renders the quantitative measure ment of each lesion in the glandular stomach quite difficult, and thus observations of the damage have been performed grossly, frequently employing "all or none" criteria.In a recent review, Cooke (2) concluded that the basis of aspirin damage to the gastric mucosa is the presence of acid in the lumen of the stomach. Thus, an attempt was made to aggravate the aspirin-induced lesions in the rat, by means of ligation of the pylorus im nmediately prior to aspirin dosing, allowing for an easier quantitation of the lesions and in crease in sensitivity of test procedure. By this method hypersecreted gastric juice is accu mulated in the stomach and at the same time the emptying of aspirin into the duodenum is completely prevented. Quite recently, Johnson (3) reported that salicylic acid signifi cantly increased the pepsin output in dogs as a result of accelerated back diffusion of HCI.Several pharmacologic agents, including antipeptic agents, were thus examined for their effects on "standardized" gastric lesions, as well as on gastric secretion in order to test the concept of aspirin-induced damage.

Nitric oxide, afferent sensory nerves, and antioxidative enzymes in the mechanism of protection mediated by tricarbonyldichlororuthenium(II) dimer and sodium hydrosulfide against aspirin-induced gastric damage

“…Previous studies have documented that the mechanism of aspirin-induced gastric damage involves an inhibition of cytoprotective prostaglandin E 2 production via COX-1/ COX-2 enzymatic activity and the prominent fall in GBF leading to the formation of severe hemorrhagic lesions of gastric mucosa [5,[29][30][31][32][33]. On the other hand, recent studies reported that the endogenous gaseous mediators H 2 S, CO, and NO contribute to the maintenance of gastric mucosal integrity and prevent the formation of gastric mucosal lesions induced by various noxious stimuli, such as exposure to stress or administration of ethanol, bisphosphonates, and NSAIDs, including aspirin [5,17,19,21,22,26,34].…”

“…Reverse transcription to complementary DNA was performed with a high-capacity complementary DNA reverse transcription kit (Thermo Fisher Scientific, Life Technologies, MA, USA). Expression of b-actin, heme oxygenase 1 (HO-1), cyclooxygenase (COX)-2, inducible NOS (iNOS), interleukin-1b (IL-1b), GPx-1, and SOD-2 was determined by real-time PCR using specific primers [17,22], SG qPCR master mix (29) including SYBR Green (EURx, Gdansk, Poland), and Quant Studio 12K Flex thermal cycler (Thermo Fisher Scientific, MA, USA). To determine a-CGRP mRNA expression, 5 0 -GCTCACCAGGGAGG-CATCAT-3 0 forward primer and 5 0 -ATGCCTGGTA-CAGGAGCAAGA-3 0 reverse primer were used.…”

Effects of Cl-1700 and Its Constituents on Acute or Chronic Gastric Lesions and Gastric Secretion in Rats

“…As new findings, we found that the constituents of CL-1700, i.e., L-carnosine, N-acetyl-L-carnosine, and Al(OH)3 or the combination of N-acetyl-L-carnosine and Al(OH) 3 at the doses contained in the effective doses of CL-1700 had little or no effects on Shay ulcers, indomethacin induced erosions (p.o. ), or water-immersion stress induced erosions (i.p.).…”

“…raised the pH value and significantly reduced the acid output, respectively. Shay ulcers or gastric lesions induced by water immersion stress, aspirin, indomethacin, or histamine are inhibited by potent antisecretory agents such as anticholinergic agents or histamine H2-receptor antagonists (3)(4)(5). Thus, the anti-lesion activity of CL-1700 might be partly caused by its antisecretory properties.…”

Pharmacological Profile of Gastric Mucosal Protection by Marmin and Nobiletin from a Traditional Herbal Medicine, Aurantii Fructus Immaturus

“…The mechanism by which ethanol induces gastric damage is thought to be due to the disruption of the defensive factors such as the gastric mucosal barrier, gastric mucus and mucosal circu lation (14,15). On the contrary, gastric acid plays a cru cial role in the development of the aspirin-induced gastric lesions (16). The gastric lesion induced by ethanol was markedly prevented by drugs increasing the defensive fac tors, while the lesion induced by aspirin was prevented by drugs inhibiting the aggressive factors such as gastric acid (17,18).…”