Decreased gastric tone and delayed gastric emptying precede neutrophil infiltration and mucosal lesion formation in indomethacin-induced gastric damage in rats

Abstract

Gastric antral dysmotility has been implicated in the pathogenesis of indomethacin-induced gastric damage, but the relationship between gastric motor abnormalities and mucosal lesions has not been extensively studied. We investigated whether changes in gastric tone and gastric retention correlate with mucosal lesions and neutrophil migration in indomethacin-induced gastric damage in rats. Indomethacin, either 5 or 20 mg/kg , was instilled into the stomach, and then gastric damage, neutrophil migration, gastric tone and gastric retention were assessed 1 or 3 h later. Gastric damage was calculated as the sum of the lengths of all mucosal lesions, and neutrophil migration was measured by assaying myeloperoxidase activity. Gastric tone was determined by a plethysmometric method, and gastric retention of either saline or Sustacal ® was evaluated by a scintigraphic method. Gastric damage was detectable 3 h after either INDO-5 or INDO-20, but not after 1 h. Neutrophil migration was significantly higher 3 h after INDO-20 as compared with INDO-5 or control group, but not after 1 h. Values of gastric tone 1 and 3 h after either INDO-5 (1 h = 1.73 ± 0.07 ml; 3 h = 1.87 ± 0.03 ml) or (1 h = 1.70 ± 0.02 ml; 3 h = 1.79 ± 0.03 ml) were significantly lower than in controls (1 h = 1.48 ± 0.05 ml; 3 h = 1.60 ± 0.06 ml). Gastric retention of saline was higher 1 h after INDO-5 (58.9 ± 3.3%) or INDO-20 (56.1 ± 3.1%) compared to control (45.5 ± 1.7%), but not after 3 h. There were no differences concerning gastric retention of Sustacal ® between the various groups. Indomethacin induced decreased gastric tone and delayed gastric emptying, which precede mucosal lesion and neutrophil infiltration. These results indicate that there is no relationship between these gastric motor abnormalities and mucosal lesion in indomethacin-induced gastropathy.

Effect of Novel A2AAdenosine Receptor Agonist ATL 313 onClostridium difficileToxin A-Induced Murine Ileal Enteritis

“…However, there is evidence that MPO release can contribute to tissue damage during inflammation, and thus promote disease (20). MPO activity within tissues has been used to indicate neutrophil infiltration (44). The important role of neutrophils in the pathogenesis of colitis caused by infection with C. difficile and the abundant presence of neutrophils within TxA-induced pseudomembranes are well known (6,27).…”

“…The extent of neutrophil accumulation in ileal tissue was estimated by measuring MPO activity assay as previously described (44). Briefly, 50 to 100 mg of ileal tissue was homogenized in 1 ml of hexadecyltrimethylammonium bromide (HTAB) buffer for each 50 mg of tissue.…”

“…MPO is an enzyme present in the azurophil granules of neutrophils, and its presence in tissues has been used as an index of neutrophil infiltration (44). TxA (5 g/loop) caused a statistically significant increase (P Ͻ 0.05) in MPO activity in ileal tissue compared to the loops from the control group, injected with only PBS (TxA ϭ 12.6 Ϯ 2.6 versus PBS ϭ 1.6 Ϯ 0.6 U/mg).…”

Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats

“…This set of symptoms is often considered as cancer-associated dyspepsia syndrome (CADS), but its pathophysiological mechanisms are not established yet (12) . The literature shows that other types of dyspepsia, such as functional dyspepsia (23) and NSAID-induced dyspepsia (20) , could be secondary to gastrointestinal dysmotility. In the present study, we evaluated the effect of MTX-induced intestinal mucositis on gastric emptying and gastrointestinal transit of a liquid test meal in awake rats.…”

Effect of antipyrine on the gastric emptying of liquid in rats

“…Among the effects of these medications, changes in GE have been reported to be induced by aspirin, acetaminophen and indomethacin (2)(3)(4)(5)(6). Dipyrone (Dp), a phenylpyrazolone derivative mainly used for its antipyretic and analgesic properties, causes delayed GE in rats when administered at high doses (7).…”