Korean J Physiol Pharmacol.  2021 Nov;25(6):507-515. 10.4196/kjpp.2021.25.6.507.

Improved motility in the gastrointestinal tract of a postoperative ileus rat model with ilaprazole

• Kim GM
• Sohn HJ
• Choi WS
• Sohn UD

• KMID: 2521476
• DOI: http://doi.org/10.4196/kjpp.2021.25.6.507

Abstract

Postoperative ileus (POI), a symptom that occurs after abdominal surgery, reduces gastrointestinal motility. Although its mechanism is unclear, POI symptoms are known to be caused by inflammation 6 to 72 h after surgery. As proton pump inhibitors exhibit protective effect against acute inflammation, the purpose of this study was to determine the effect of ilaprazole on a POI rat model. POI was induced in rats by abdominal surgery. Rats were divided into six groups: control: normal rat + 0.5% CMC-Na, vehicle: POI rat + 0.5% CMC-Na, mosapride: POI rat + mosapride 2 mg/kg, ilaprazole 1 mg/kg: POI rat + ilaprazole 1 mg/kg, ilaprazole 3 mg/kg: POI rat + ilaprazole 3 mg/kg, and ilaprazole 10 mg/kg: POI rat + ilaprazole 10 mg/kg. Gastrointestinal motility was confirmed by measuring gastric emptying (GE) and gastrointestinal transit (GIT). In the small intestine, inflammation was confirmed by measuring TNF-α and IL-1β; oxidative stress was confirmed by SOD, GSH, and MDA levels; and histological changes were observed by H&E staining. Based on the findings, GE and GIT were decreased in the vehicle group and improved in the ilaprazole 10 mg/kg group. In the ilaprazole 10 mg/kg group, TNF-α and IL-1β levels were decreased, SOD and GSH levels were increased, and MDA levels were decreased. Histological damage was also reduced in the ilaprazole-treated groups. These findings suggest that ilaprazole prevents the decrease in gastrointestinal motility, a major symptom of postoperative ileus, and reduces inflammation and oxidative stress.

Keyword

Gastrointestinal tract; Ilaprazole; Inflammation; Postoperative ileus

Figure

• 

  Fig. 1 Effect of ilaprazole on gastric emptying (GE) in stomach of each group. The recovery effect of the ilaprazole on GE in postoperative ileus (POI) model of rats. The GE value was measured from the rat stomach and the absorbance at 590 nm was measured (n = 5–6). Control: not open the abdomen treated with 4 ml/kg 0.5 % CMC-Na; vehicle: POI rats treated with 4 ml/kg 0.5 % CMC-Na; ilaprazole 1 mg/kg: POI rats treated with ilaprazole 1 mg/kg; ilaprazole 3 mg/kg: POI rats treated with ilaprazole 3 mg/kg; ilaprazole 10 mg/kg: POI rats treated with ilaprazole 10 mg/kg; Data were expressed as means ± SEM. Dunnett’s test was performed post-hoc for the ANOVA. *p < 0.05 vs. control group, #p < 0.05 vs. vehicle group.

• 

  Fig. 2 Effect of ilaprazole on GIT in small intestine of each group. The MGC value was measured from the rat stomach and the absorbance at 590 nm was measured (n = 4–6). Control: not open the abdomen treated with 4 ml/kg 0.5 % CMC-Na; vehicle: POI rats treated with 4 ml/kg 0.5 % CMC-Na; ilaprazole 1 mg/kg: POI rats treated with ilaprazole 1 mg/kg; ilaprazole 3 mg/kg: POI rats treated with ilaprazole 3 mg/kg; ilaprazole 10 mg/kg: POI rats treated with ilaprazole 10 mg/kg; The data were expressed as means ± SEM. Dunnett’s test was performed post-hoc for the ANOVA. GIT, gastrointestinal transit; MGC, mean geometric center; POI, postoperative ileus. **p < 0.01 vs. control group, #p < 0.05 vs. vehicle group.

• 

  Fig. 3 Effect of ilaprazole on tumor necrosis factor (TNF)-α in terminal ileus of each group. Anti-inflammation effect of the ilaprazole at the terminal ileus of the postoperative ileus (POI)-induced rats. TNF-α concentration was detected absorbance in 450 nm (n = 5–6). Control: not open the abdomen treated with 4 ml/kg 0.5% CMC-Na; vehicle: POI rats treated with 4 ml/kg 0.5 % CMC-Na; ilaprazole 1 mg/kg: POI rats treated with ilaprazole 1 mg/kg; ilaprazole 3 mg/kg: POI rats treated with ilaprazole 3 mg/kg; ilaprazole 10 mg/kg: POI rats treated with ilaprazole 10 mg/kg; The data was expressed as means ± SEM. Dunnett’s test was performed post-hoc for the ANOVA. ***p < 0.001 vs. control group, ##p < 0.01 and ###p < 0.001 vs. vehicle group.

• 

  Fig. 4 Effect of ilaprazole on interleukin (IL)-1β in terminal ileus of each group. Anti-inflammation effect of the ilaprazole at the terminal ileus of the postoperative ileus (POI)-induced rats. IL-1β concentration was detected absorbance in 450 nm (n = 6). Control: not open the abdomen treated with 4 ml/kg 0.5 % CMC-Na; vehicle: POI rats treated with 4 ml/kg 0.5 % CMC-Na; ilaprazole 1 mg/kg: POI rats treated with ilaprazole 1 mg/kg; ilaprazole 3 mg/kg: POI rats treated with ilaprazole 3 mg/kg; ilaprazole 10 mg/kg: POI rats treated with ilaprazole 10 mg/kg; The data was expressed as means ± SEM. Dunnett’s test was performed post-hoc for the ANOVA. ***p < 0.001 vs. control group, ##p < 0.01, ###p < 0.001 vs. vehicle group.

• 

  Fig. 5 Effect of ilaprazole administration on structural damage of small intestine in each experimental group. Histology of terminal ileus of each group. The structural damage was identified histologically in terminal ileus of each group (black arrow: swelling, red arrow: structural damages). (A) Control group; (B) vehicle group; (C) mosa group; (D) ilaprazole 1 mg/kg group; (E) ilaprazole 3 mg/kg group; (F) ilaprazole 10 mg/kg group. Photomicrographs were taken at a magnification of ×200, H&E.

• 

  Fig. 6 Effect of ilaprazole on oxidative stress in terminal ileus of each group. Antioxidative effect of the ilaprazole at the terminal ileus of the POI-induced rats. (A) SOD, (B) GSH, and (C) MDA concentrations were detected absorbance in 450 nm (n = 5–6). Control: not open the abdomen treated with 4 ml/kg 0.5% CMC-Na; vehicle: POI rats treated with 4 ml/kg 0.5 % CMC-Na; ilaprazole 1 mg/kg: POI rats treated with ilaprazole 1 mg/kg; ilaprazole 3 mg/kg: POI rats treated with ilaprazole 3 mg/kg; ilaprazole 10 mg/kg: POI rats treated with ilaprazole 10 mg/kg; The data was expressed as means ± SEM. Dunnett’s test was performed post-hoc for the ANOVA. POI, postoperative ileus; SOD, superoxide dismutase; GSH, glutathione; MDA, malondialdehyde. **p < 0.01 and ***p < 0.001 vs. control group, #p < 0.05 and ##p < 0.01 vs. vehicle group.

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