Abstract
Background
Selective serotonin reuptake inhibitors (SSRIs) have recently become potential candidates for a new therapeutic approach to ulcer and gastric bleeding. Heat shock protein 70 (Hsp70) plays an important role in cellular resistance to nonsteroidal anti-inflammatory drugs (NSAIDs). However, there is lack of evidence that fluvoxamine recruits Hsp70 to affect stress-induced gastric ulcer. Therefore, we investigated the effect of fluvoxamine on NSAID- and stress-induced gastric ulcer and the possible involvement of Hsp70.
Methods
ICR mice were used in the study. Stress induction was made by the water-immersion-plus-restraint method. NSAID-induced gastric ulcer was produced by oral administration of indomethacin. Fluvoxamine was given orally 30 min before stress induction and indomethacin treatment.
Results
Stress and indomethacin treatment significantly increased the ulcer index and intraluminal bleeding score. Stress and indomethacin treatment also significantly increased the expression of Hsp70. Fluvoxamine significantly decreased the ulcer index and intraluminal bleeding in both ulcer models. Moreover, fluvoxamine further increased the expression of Hsp70 in the gastric tissue of stress- and indomethacin-treated mice.
Conclusions
Our results indicate that fluvoxamine may have a protective effect against stress- as well as NSAID-induced gastric ulcer. In addition, the present study suggests the possible involvement of Hsp70 in the amelioration of gastric ulcer by fluvoxamine.
Acknowledgments
We would like to show our gratitude to Tahir Professorship Program from Tahir Foundation. The authors also thank our colleagues from Department of Clinical Pharmacy Universitas Airlangga for technical assistance during this study.
Author contributions: Study conception and design: JK, MR, CA, KN, DWS, TA, S; acquisition of data: JK, MR, KN, RO, AR, YD; analysis and interpretation of data: JK, MR, CA, KN; drafting of the manuscript: MR, CA, KN, RO, AR, YD; critical revision: JK, MR, CA, RO, AR, YD, DWS, TA, S.
Research funding: The study was financially supported by Tahir Foundation.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Widiger TA, Clark LA. Toward DSM – V and the classification of psychopathology. Psychol Bull 2000;126:946–63.10.1037/0033-2909.126.6.946Search in Google Scholar PubMed
2. Cho CH, Koo MW, Garg GP, Ogle CW. Stress-induced gastric ulceration: its aetiology and clinical implications. Scand J Gastroenterol 2009;27:257–62.10.3109/00365529209000071Search in Google Scholar PubMed
3. Bertleff M, Lange J. Perforated peptic ulcer disease: a review of history and treatment. Dig Surg 2010;27:161–9.10.1159/000264653Search in Google Scholar PubMed
4. Zelickson M, Bronder C, Johnson B, Camunas J, Smith D, Rawlinson D, et al. Helicobacter pylori is not the predominant etiology for peptic ulcers requiring operation. Am Surg 2011;77:1054–60.10.1177/000313481107700827Search in Google Scholar
5. Bardou M, Quenot J-P, Barkun A. Stress-related mucosal disease in the critically ill patient. Nat Rev Gastroenterol Hepatol 2015;12:98–107.10.1038/nrgastro.2014.235Search in Google Scholar PubMed
6. Ali T, Harty RF. Stress-induced ulcer bleeding in critically ill patients. Gastroenterol Clin North Am 2009;38:245–65.10.1016/j.gtc.2009.03.002Search in Google Scholar PubMed
7. Sheen E, Triadafilopoulos G. Adverse effects of long-term proton pump inhibitor therapy. Dig Dis Sci 2011;56:931–50.10.1007/s10620-010-1560-3Search in Google Scholar PubMed
8. Eusebi L, Rabitti S, Artesiani M, Gelli D, Montagnani M, Zagari R, et al. Proton pump inhibitors: risks of long-term use. J Gastroenterol Hepatol 2017;32:1295–302.10.1111/jgh.13737Search in Google Scholar PubMed
9. Ji C, Fan D, Li W, Guo L, Liang Z, Xu R, et al. Evaluation of the anti-ulcerogenic activity of the antidepressants duloxetine, amitriptyline, fluoxetine and mirtazapine in different models of experimental gastric ulcer in rats. Eur J Pharmacol 2012;691:46–51.10.1016/j.ejphar.2012.06.041Search in Google Scholar PubMed
10. Abdel-Sater K, Abdel-Daiem W, Bakheet M. The gender difference of selective serotonin reuptake inhibitor, fluoxetine in adult rats with stress-induced gastric ulcer. Eur J Pharmacol 2012;688:42–8.10.1016/j.ejphar.2012.04.019Search in Google Scholar PubMed
11. Takahashi T, Suzuki G, Nibuya M, Tanaka T, Nozawa H, Hatano B, et al. Therapeutic effect of paroxetine on stress-induced gastric lesions in mice. Prog Neuropsychopharmacol Biol Psychiatry 2012;36:39–43.10.1016/j.pnpbp.2011.08.017Search in Google Scholar PubMed
12. Westenberg HG, Sandner C. Tolerability and safety of fluvoxamine and other antidepressants. Int J Clin Pract 2006;60:482–91.10.1111/j.1368-5031.2006.00865.xSearch in Google Scholar PubMed PubMed Central
13. Dursun H, Bilici M, Albayrak F, Ozturk C, Saglam MB, Alp HH, et al. Antiulcer activity of fluvoxamine in rats and its effect on oxidant and antioxidant parameters in stomach tissue. BMC Gastroenterol 2009;9:36.10.1186/1471-230X-9-36Search in Google Scholar PubMed PubMed Central
14. Jolly C, Morimoto R. Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst 2000;92:1564–72.10.1093/jnci/92.19.1564Search in Google Scholar PubMed
15. Basu S, Binder RJ, Suto R, Anderson KM, Srivastava PK. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway. Int Immunol 2000;12:1539–46.10.1093/intimm/12.11.1539Search in Google Scholar PubMed
16. Hartl F, Hayer-Hartl M. Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 2002;295:1852–8.10.1126/science.1068408Search in Google Scholar PubMed
17. Johnson J, Fleshner M. Releasing signals, secretory pathways, and immune function of endogenous extracellular heat shock protein 72. J Leukoc Biol 2006;79:425–34.10.1189/jlb.0905523Search in Google Scholar PubMed
18. Suemasu S, Tanaka K, Namba T, Ishihara T, Katsu T, Fujimoto M, et al. A role for HSP70 in protecting against indomethacin-induced gastric lesions. J Biol Chem 2009;284:19705–15.10.1074/jbc.M109.006817Search in Google Scholar PubMed PubMed Central
19. Suleyman H, Cadirci E, Albayrak A, Polat B, Halici Z, Koc F, et al. Comparative study on the gastroprotective potential of some antidepressants in indomethacin-induced ulcer in rats. Chem Biol Interact 2009;180:318–24.10.1016/j.cbi.2009.03.002Search in Google Scholar PubMed
20. Chiu P, Barnett A, Tetzloff G, Kaminski J. Gastric antisecretory properties of SCH 32651. Arch Int Pharmacodyn Ther 1984;270:116–27.Search in Google Scholar
21. Su TC, Lin SH, Lee PT, Yeh SH, Hsieh TH, Chou SY, et al. The sigma-1 receptor-zinc finger protein 179 pathway protects against hydrogen peroxide-induced cell injury. Neuropharmacology 2016;105:1–9.10.1016/j.neuropharm.2016.01.015Search in Google Scholar PubMed PubMed Central
22. Dalery J, Honig A. Fluvoxamine versus fluoxetine in major depressive episode: a double-blind randomised comparison. Hum Psychopharmacol 2003;18:379–84.10.1002/hup.490Search in Google Scholar PubMed
23. Chang X, Peng L, Yi S, Peng Y, Yan J. Association of high expression in rat gastric mucosal heat shock protein 70 induced by moxibustion pretreatment with protection against stress injury. World J Gastroenterol 2007;13: 4355–9.10.3748/wjg.v13.i32.4355Search in Google Scholar PubMed PubMed Central
24. Ortega-Roldan J, Ossa F, Schnell J. Characterization of the human sigma-1 receptor chaperone domain structure and binding immunoglobulin protein (BIP) interactions. J Biol Chem 2013;288:21448–57.10.1074/jbc.M113.450379Search in Google Scholar PubMed PubMed Central
©2019 Walter de Gruyter GmbH, Berlin/Boston
