Browse > Article
http://dx.doi.org/10.4196/kjpp.2021.25.6.507

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

Kim, Geon Min (Department of Pharmacology, College of Pharmacy, Chung-Ang University)
Sohn, Hee Ju (Department of Surgery, Chung-Ang University Hospital, Chung-Ang University)
Choi, Won Seok (Department of Pharmacology, College of Pharmacy, Chung-Ang University)
Sohn, Uy Dong (Department of Pharmacology, College of Pharmacy, Chung-Ang University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.25, no.6, 2021 , pp. 507-515 More about this Journal
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.
Keywords
Gastrointestinal tract; Ilaprazole; Inflammation; Postoperative ileus;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Luszczak J, Ziaja-Soltys M, Rzymowska J. Anti-oxidant activity of superoxide dismutase and glutathione peroxidase enzymes in skeletal muscles from slaughter cattle infected with Taenia saginata. Exp Parasitol. 2011;128:163-165.   DOI
2 Wang Y, Branicky R, Noe A, Hekimi S. Superoxide dismutases: dual roles in controlling ROS damage and regulating ROS signaling. J Cell Biol. 2018;217:1915-1928.   DOI
3 Qin S, McLaughlin AP, De Vries GW. Protection of RPE cells from oxidative injury by 15-deoxy-delta12,14-prostaglandin J2 by augmenting GSH and activating MAPK. Invest Ophthalmol Vis Sci. 2006;47:5098-5105.   DOI
4 Lawrence L, Menon S, Vincent S, Sivaram VP, Padikkala J. Radical scavenging and gastroprotective activity of methanolic extract of Gmelina arborea stem bark. J Ayurveda Integr Med. 2016;7:78-82.   DOI
5 Akinrinmade FJ, Akinrinde AS, Soyemi OO, Oyagbemi AA. Antioxidant potential of the methanol extract of Parquetina nigrescens mediates protection against intestinal ischemia-reperfusion injury in rats. J Diet Suppl. 2016;13:420-432.   DOI
6 Sanger GJ. 5-Hydroxytryptamine and the gastrointestinal tract: where next? Trends Pharmacol Sci. 2008;29:465-471.   DOI
7 Tevis SE, Carchman EH, Foley EF, Harms BA, Heise CP, Kennedy GD. Postoperative ileus--more than just prolonged length of stay? J Gastrointest Surg. 2015;19:1684-1690.   DOI
8 Li YY, Cao MH, Goetz B, Chen CQ, Feng YJ, Chen CJ, Kasparek MS, Sibaev A, Storr M, Kreis ME. The dual effect of cannabinoid receptor-1 deficiency on the murine postoperative ileus. PLoS One. 2013;8:e67427.   DOI
9 Gero D, Gie O, Hubner M, Demartines N, Hahnloser D. Postoperative ileus: in search of an international consensus on definition, diagnosis, and treatment. Langenbecks Arch Surg. 2017;402:149-158.   DOI
10 Livingston EH, Passaro EP Jr. Postoperative ileus. Dig Dis Sci. 1990;35:121-132.   DOI
11 Stakenborg N, Gomez-Pinilla PJ, Boeckxstaens GE. Postoperative Ileus: pathophysiology, current therapeutic approaches. Handb Exp Pharmacol. 2017;239:39-57.
12 Chen FF, Zhou CJ, Zhuang CL, Huang DD, Lu JX, Shen X, Chen XL, Yu Z. Mitochondrial energy metabolism disorder and apoptosis: a potential mechanism of postoperative ileus. Int J Clin Exp Med. 2015;8:14885-14895.
13 Endo M, Hori M, Ozaki H, Oikawa T, Hanawa T. Daikenchuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus by anti-inflammatory action through nicotinic acetylcholine receptors. J Gastroenterol. 2014;49:1026-1039.   DOI
14 Ellozy SH, Harris MT, Bauer JJ, Gorfine SR, Kreel I. Early postoperative small-bowel obstruction: a prospective evaluation in 242 consecutive abdominal operations. Dis Colon Rectum. 2002;45:1214-1217.   DOI
15 Holte K, Kehlet H. Postoperative ileus: progress towards effective management. Drugs. 2002;62:2603-2615.   DOI
16 Lubbers T, Buurman W, Luyer M. Controlling postoperative ileus by vagal activation. World J Gastroenterol. 2010;16:1683-1687.   DOI
17 Farro G, Gomez-Pinilla PJ, Di Giovangiulio M, Stakenborg N, Auteri M, Thijs T, Depoortere I, Matteoli G, Boeckxstaens GE. Smooth muscle and neural dysfunction contribute to different phases of murine postoperative ileus. Neurogastroenterol Motil. 2016;28:934-947.   DOI
18 Stakenborg N, Labeeuw E, Gomez-Pinilla PJ, De Schepper S, Aerts R, Goverse G, Farro G, Appeltans I, Meroni E, Stakenborg M, Viola MF, Gonzalez-Dominguez E, Bosmans G, Alpizar YA, Wolthuis A, D'Hoore A, Van Beek K, Verheijden S, Verhaegen M, Derua R, et al. Preoperative administration of the 5-HT4 receptor agonist prucalopride reduces intestinal inflammation and shortens postoperative ileus via cholinergic enteric neurons. Gut. 2019;68:1406-1416.   DOI
19 Boeckxstaens GE, de Jonge WJ. Neuroimmune mechanisms in postoperative ileus. Gut. 2009;58:1300-1311.   DOI
20 Wehner S, Schwarz NT, Hundsdoerfer R, Hierholzer C, Tweardy DJ, Billiar TR, Bauer AJ, Kalff JC. Induction of IL-6 within the rodent intestinal muscularis after intestinal surgical stress. Surgery. 2005;137:436-446.   DOI
21 Kreiss C, Birder LA, Kiss S, VanBibber MM, Bauer AJ. COX-2 dependent inflammation increases spinal Fos expression during rodent postoperative ileus. Gut. 2003;52:527-534.   DOI
22 Kalff JC, Buchholz BM, Eskandari MK, Hierholzer C, Schraut WH, Simmons RL, Bauer AJ. Biphasic response to gut manipulation and temporal correlation of cellular infiltrates and muscle dysfunction in rat. Surgery. 1999;126:498-509.   DOI
23 Ozkan N, Ersoy OF, Ozsoy Z, Cakir E. Melatonin exhibits supportive effects on oxidants and anastomotic healing during intestinal ischemia/reperfusion injury. Ulus Travma Acil Cerrahi Derg. 2018;24:1-8.
24 Rychter J, Clave P. Intestinal inflammation in postoperative ileus: pathogenesis and therapeutic targets. Gut. 2013;62:1534-1535.   DOI
25 Kalff JC, Schraut WH, Billiar TR, Simmons RL, Bauer AJ. Role of inducible nitric oxide synthase in postoperative intestinal smooth muscle dysfunction in rodents. Gastroenterology. 2000;118:316-327.   DOI
26 Turan A, Celik I. Antioxidant and hepatoprotective properties of dried fig against oxidative stress and hepatotoxicity in rats. Int J Biol Macromol. 2016;91:554-559.   DOI
27 Fujita H, Fujishima H, Chida S, Takahashi K, Qi Z, Kanetsuna Y, Breyer MD, Harris RC, Yamada Y, Takahashi T. Reduction of renal superoxide dismutase in progressive diabetic nephropathy. J Am Soc Nephrol. 2009;20:1303-1313.   DOI
28 Liu W, Xu Z, Li H, Guo M, Yang T, Feng S, Xu B, Deng Y. Protective effects of curcumin against mercury-induced hepatic injuries in rats, involvement of oxidative stress antagonism, and Nrf2-ARE pathway activation. Hum Exp Toxicol. 2017;36:949-966.   DOI
29 Toyomasu Y, Mochiki E, Morita H, Ogawa A, Yanai M, Ohno T, Fujii T, Tsutsumi S, Asao T, Kuwano H. Mosapride citrate improves postoperative ileus of patients with colectomy. J Gastrointest Surg. 2011;15:1361-1367.   DOI
30 van Bree SH, Nemethova A, Cailotto C, Gomez-Pinilla PJ, Matteoli G, Boeckxstaens GE. New therapeutic strategies for postoperative ileus. Nat Rev Gastroenterol Hepatol. 2012;9:675-683.   DOI
31 Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep. 2008;10:528-534.   DOI
32 da Silva LM, Boeing T, Somensi LB, Cury BJ, Steimbach VM, Silveria AC, Niero R, Cechinel Filho V, Santin JR, de Andrade SF. Evidence of gastric ulcer healing activity of Maytenus robusta Reissek: in vitro and in vivo studies. J Ethnopharmacol. 2015;175:75-85.   DOI
33 Zhuang CL, Chen FF, Lu JX, Zheng BS, Liu S, Zhou CJ, Huang DD, Shen X, Yu Z. Impact of different surgical traumas on postoperative ileus in rats and the mechanisms involved. Int J Clin Exp Med. 2015;8:16778-16786.
34 Den Boer PJ, Poot M, Verkerk A, Jansen R, Mackenbach P, Grootegoed JA. Glutathione-dependent defence mechanisms in isolated round spermatids from the rat. Int J Androl. 1990;13:26-38.   DOI
35 De Backer O, Elinck E, Blanckaert B, Leybaert L, Motterlini R, Lefebvre RA. Water-soluble CO-releasing molecules reduce the development of postoperative ileus via modulation of MAPK/HO-1 signalling and reduction of oxidative stress. Gut. 2009;58:347-356.   DOI
36 Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol. 1990;186:407-421.   DOI
37 Valenzuela A. The biological significance of malondialdehyde determination in the assessment of tissue oxidative stress. Life Sci. 1991;48:301-309.   DOI
38 Curran MP, Robinson DM. Mosapride in gastrointestinal disorders. Drugs. 2008;68:981-991.   DOI
39 Odaka T, Suzuki T, Seza A, Yamaguchi T, Saisho H. [Serotonin 5-HT4 receptor agonist (mosapride citrate)]. Nihon Rinsho. 2006;64:1491-1494. Japanese.
40 Tsuchida Y, Hatao F, Fujisawa M, Murata T, Kaminishi M, Seto Y, Hori M, Ozaki H. Neuronal stimulation with 5-hydroxytryptamine 4 receptor induces anti-inflammatory actions via α7nACh receptors on muscularis macrophages associated with postoperative ileus. Gut. 2011;60:638-647.   DOI
41 Balza E, Piccioli P, Carta S, Lavieri R, Gattorno M, Semino C, Castellani P, Rubartelli A. Proton pump inhibitors protect mice from acute systemic inflammation and induce long-term cross-tolerance. Cell Death Dis. 2016;7:e2304.   DOI
42 Okamoto A, Kohama K, Aoyama-Ishikawa M, Yamashita H, Fujisaki N, Yamada T, Yumoto T, Nosaka N, Naito H, Tsukahara K, Iida A, Sato K, Kotani J, Nakao A. Intraperitoneally administered, hydrogen-rich physiologic solution protects against postoperative ileus and is associated with reduced nitric oxide production. Surgery. 2016;160:623-631.   DOI
43 Murakami H, Li S, Foreman R, Yin J, Hirai T, Chen JDZ. Intraoperative vagus nerve stimulation accelerates postoperative recovery in rats. J Gastrointest Surg. 2019;23:320-330.   DOI
44 Murakami H, Li S, Foreman R, Yin J, Hirai T, Chen JDZ. Ameliorating effects of electroacupuncture on dysmotility, inflammation, and pain mediated via the autonomic mechanism in a rat model of postoperative ileus. J Neurogastroenterol Motil. 2019;25:286-299.   DOI
45 Nam Y, Lee JM, Wang Y, Ha HS, Sohn UD. The effect of Flos Lonicerae Japonicae extract on gastro-intestinal motility function. J Ethnopharmacol. 2016;179:280-290.   DOI
46 Barquist E, Zinner M, Rivier J, Tache Y. Abdominal surgery-induced delayed gastric emptying in rats: role of CRF and sensory neurons. Am J Physiol. 1992;262(4 Pt 1):G616-G620.
47 Asgeirsson T, El-Badawi KI, Mahmood A, Barletta J, Luchtefeld M, Senagore AJ. Postoperative ileus: it costs more than you expect. J Am Coll Surg. 2010;210:228-231.   DOI
48 Kalff JC, Carlos TM, Schraut WH, Billiar TR, Simmons RL, Bauer AJ. Surgically induced leukocytic infiltrates within the rat intestinal muscularis mediate postoperative ileus. Gastroenterology. 1999;117:378-387.   DOI
49 Chubineh S, Birk J. Proton pump inhibitors: the good, the bad, and the unwanted. South Med J. 2012;105:613-618.   DOI
50 Stoffels B, Hupa KJ, Snoek SA, van Bree S, Stein K, Schwandt T, Vilz TO, Lysson M, Veer CV, Kummer MP, Hornung V, Kalff JC, de Jonge WJ, Wehner S. Postoperative ileus involves interleukin-1 receptor signaling in enteric glia. Gastroenterology. 2014;146:176-187. e1.   DOI
51 Xiong YJ, Chu HW, Lin Y, Han F, Li YC, Wang AG, Wang FJ, Chen DP, Wang JY. Hesperidin alleviates rat postoperative ileus through anti-inflammation and stimulation of Ca2+-dependent myosin phosphorylation. Acta Pharmacol Sin. 2016;37:1091-1100.   DOI