Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
December-2021 Volume 22 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2021 Volume 22 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Roflumilast, a type of phosphodiesterase 4 inhibitor, can reduce intestinal injury caused by sepsis

  • Authors:
    • Zhongyuan Zhang
    • Meifeng Liang
    • Xiongfei Wan
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430060, P.R. China, Department of Medical Insurance and Management, CR & WISCO General Hospital, Wuhan, Hubei 430000, P.R. China, Department of Pharmacy, CR & WISCO General Hospital, Wuhan, Hubei 430000, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 1398
    |
    Published online on: October 1, 2021
       https://doi.org/10.3892/etm.2021.10834
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Sepsis is a systemic inflammatory response syndrome caused by infection, which has a complex mechanism. The gastrointestinal tract is commonly the first organ affected by sepsis, but intestinal disease itself can also induce sepsis. Roflumilast has been found to exert anti‑inflammatory effects and, thus, the present study sought to examine its effect on intestinal damage caused by sepsis. In vivo studies were conducted using cecal ligation and puncture rat models, and in vitro experiments were performed using IEC‑6 cells. The intestinal cells were first induced with lipopolysaccharide and the induced cells were then treated with roflumilast to evaluate its effects on phosphodiesterase (PDE)4 expression, intestinal function indices, release of inflammatory factors and cell apoptosis. The expression level of PDE4 in the small intestinal tissue of septic rats was found to be significantly higher compared with that in the normal group, suggesting that PDE4 may play a key role in intestinal injury caused by sepsis. It was found that roflumilast reduced PDE4 expression, as well as the levels of intestinal function indices, including lactate dehydrogenase, diamino oxidase and intestinal fatty acid‑binding protein, in intestinal cells. Moreover, roflumilast reduced cellular damage, the release of inflammatory factors and apoptosis. In summary, the findings of the present study indicated that roflumilast can relieve the inflammation and apoptosis of intestinal cells caused by sepsis and can promote their functional recovery. These findings may promote the expansion of the clinical application of roflumilast in the future.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Faix JD: Biomarkers of sepsis. Crit Rev Clin Lab Sci. 50:23–36. 2013.PubMed/NCBI View Article : Google Scholar

2 

Huang M, Cai S and Su J: The pathogenesis of sepsis and potential therapeutic targets. Int J Mol Sci. 20(5376)2019.PubMed/NCBI View Article : Google Scholar

3 

Martin GS: Sepsis, severe sepsis and septic shock: Changes in incidence, pathogens and outcomes. Expert Rev Anti Infect Ther. 10:701–706. 2012.PubMed/NCBI View Article : Google Scholar

4 

Rossaint J and Zarbock A: Pathogenesis of multiple organ failure in sepsis. Crit Rev Immunol. 35:277–291. 2015.PubMed/NCBI View Article : Google Scholar

5 

Huang CT, Tsai YJ, Tsai PR, Yu CJ and Ko WJ: Epidemiology and outcome of severe sepsis and septic shock in surgical intensive care units in Northern Taiwan. Medicine (Baltimore). 94(e2136)2015.PubMed/NCBI View Article : Google Scholar

6 

Martinez A and Gil C: cAMP-specific phosphodiesterase inhibitors: Promising drugs for inflammatory and neurological diseases. Expert Opin Ther Pat. 24:1311–1321. 2014.PubMed/NCBI View Article : Google Scholar

7 

Lynch MJ, Hill EV and Houslay MD: Intracellular targeting of phosphodiesterase-4 underpins compartmentalized cAMP signaling. Curr Top Dev Biol. 75:225–259. 2006.PubMed/NCBI View Article : Google Scholar

8 

Ioakeimidis N and Kostis JB: Pharmacologic therapy for erectile dysfunction and its interaction with the cardiovascular system. J Cardiovasc Pharmacol Ther. 19:53–64. 2014.PubMed/NCBI View Article : Google Scholar

9 

Peng T, Qi B, He J, Ke H and Shi J: Advances in the development of phosphodiesterase-4 inhibitors. J Med Chem. 63:10594–10617. 2020.PubMed/NCBI View Article : Google Scholar

10 

Di Luigi L, Sansone M, Sansone A, Ceci R, Duranti G, Borrione P, Crescioli C, Sgrò P and Sabatini S: Phosphodiesterase type 5 inhibitors, sport and doping. Curr Sports Med Rep. 16:443–447. 2017.PubMed/NCBI View Article : Google Scholar

11 

Xu M, Yu X, Meng X, Huang S, Zhang Y, Zhang A and Jia Z: Inhibition of PDE4/PDE4B improves renal function and ameliorates inflammation in cisplatin-induced acute kidney injury. Am J Physiol Renal Physiol. 318:F576–F588. 2020.PubMed/NCBI View Article : Google Scholar

12 

Sakkas LI, Mavropoulos A and Bogdanos DP: Phosphodiesterase 4 inhibitors in immune-mediated diseases: Mode of action, clinical applications, current and future perspectives. Curr Med Chem. 24:3054–3067. 2017.PubMed/NCBI View Article : Google Scholar

13 

Myers SA, Gobejishvili L, Saraswat Ohri S, Garrett Wilson C, Andres KR, Riegler AS, Donde H, Joshi-Barve S, Barve S and Whittemore SR: Following spinal cord injury, PDE4B drives an acute, local inflammatory response and a chronic, systemic response exacerbated by gut dysbiosis and endotoxemia. Neurobiol Dis. 124:353–363. 2019.PubMed/NCBI View Article : Google Scholar

14 

Feng H, Chen J, Wang H, Cheng Y, Zou Z, Zhong Q and Xu J: Roflumilast reverses polymicrobial sepsis-induced liver damage by inhibiting inflammation in mice. Lab Invest. 97:1008–1019. 2017.PubMed/NCBI View Article : Google Scholar

15 

Chang X, Hu LF, Ma XJ, Yin J, Liu XY and Li JB: Influence of roflumilast on sepsis mice through the JAK/STAT signaling pathway. Eur Rev Med Pharmacol Sci. 23:1335–1341. 2019.PubMed/NCBI View Article : Google Scholar

16 

Xu X, Liao L, Hu B, Jiang H and Tan M: Roflumilast, a phosphodiesterases-4 (PDE4) inhibitor, alleviates sepsis-induced acute kidney injury. Med Sci Monit. 26(e921319)2020.PubMed/NCBI View Article : Google Scholar

17 

El-Ashmawy NE, Khedr NF, El-Bahrawy HA and El-Adawy SA: Roflumilast, type 4 phosphodiesterase inhibitor, attenuates inflammation in rats with ulcerative colitis via down-regulation of iNOS and elevation of cAMP. Int Immunopharmacol. 56:36–42. 2018.PubMed/NCBI View Article : Google Scholar

18 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

19 

Stoller J, Halpin L, Weis M, Aplin B, Qu W, Georgescu C and Nazzal M: Epidemiology of severe sepsis: 2008-2012. J Crit Care. 31:58–62. 2016.PubMed/NCBI View Article : Google Scholar

20 

Sertaridou E, Papaioannou V, Kolios G and Pneumatikos I: Gut failure in critical care: Old school versus new school. Ann Gastroenterol. 28:309–322. 2015.PubMed/NCBI

21 

Yang H, Song Z, Jin H, Cui Y, Hou M and Gao Y: Protective effect of rhBNP on intestinal injury in the canine models of sepsis. Int Immunopharmacol. 19:262–266. 2014.PubMed/NCBI View Article : Google Scholar

22 

Deitch EA: Bacterial translocation or lymphatic drainage of toxic products from the gut: What is important in human beings? Surgery. 131:241–244. 2002.PubMed/NCBI View Article : Google Scholar

23 

Deitch EA, Xu D and Kaise VL: Role of the gut in the development of injury- and shock induced SIRS and MODS: The gut-lymph hypothesis, a review. Front Biosci. 11:520–528. 2006.PubMed/NCBI View Article : Google Scholar

24 

Li H, Fan C, Feng C, Wu Y, Lu H, He P, Yang X, Zhu F, Qi Q, Gao Y, et al: Inhibition of phosphodiesterase-4 attenuates murine ulcerative colitis through interference with mucosal immunity. Br J Pharmacol. 176:2209–2226. 2019.PubMed/NCBI View Article : Google Scholar

25 

Kumar P, Nagarajan A and Uchil PD: Analysis of cell viability by the lactate dehydrogenase assay. Cold Spring Harb Protoc. 2018:2018.PubMed/NCBI View Article : Google Scholar

26 

Wolvekamp MC and de Bruin RW: Diamine oxidase: An overview of historical, biochemical and functional aspects. Dig Dis. 12:2–14. 1994.PubMed/NCBI View Article : Google Scholar

27 

Derikx JP, Schellekens DH and Acosta S: Serological markers for human intestinal ischemia: A systematic review. Best Pract Res Clin Gastroenterol. 31:69–74. 2017.PubMed/NCBI View Article : Google Scholar

28 

Sakai M, Suzuki T, Tomita K, Yamashita S, Palikhe S, Hattori K, Yoshimura N, Matsuda N and Hattori Y: Diminished responsiveness to dobutamine as an inotrope in mice with cecal ligation and puncture-induced sepsis: Attribution to phosphodiesterase 4 upregulation. Am J Physiol Heart Circ Physiol. 312:H1224–H1237. 2017.PubMed/NCBI View Article : Google Scholar

29 

Gong S, Chen Y, Meng F, Zhang Y, Li C, Zhang G, Huan W and Wu F: Roflumilast enhances cisplatin-sensitivity and reverses cisplatin-resistance of ovarian cancer cells via cAMP/PKA/CREB-FtMt signalling axis. Cell Prolif. 51(e12474)2018.PubMed/NCBI View Article : Google Scholar

30 

Takano A, Uz T, Garcia-Segovia J, Tsai M, Lahu G, Amini N, Nakao R, Jia Z and Halldin C: A nonhuman primate PET study: Measurement of brain PDE4 occupancy by roflumilast using (R)-[11C]Rolipram. Mol Imaging Biol. 20:615–622. 2018.PubMed/NCBI View Article : Google Scholar

31 

Peng S, Yan HZ, Liu PR, Shi XW, Liu CL, Liu Q and Zhang Y: Phosphodiesterase 4 inhibitor roflumilast protects rat hippocampal neurons from sevoflurane induced injury via modulation of MEK/ERK signaling pathway. Cell Physiol Biochem. 45:2329–2337. 2018.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang Z, Liang M and Wan X: Roflumilast, a type of phosphodiesterase 4 inhibitor, can reduce intestinal injury caused by sepsis. Exp Ther Med 22: 1398, 2021.
APA
Zhang, Z., Liang, M., & Wan, X. (2021). Roflumilast, a type of phosphodiesterase 4 inhibitor, can reduce intestinal injury caused by sepsis. Experimental and Therapeutic Medicine, 22, 1398. https://doi.org/10.3892/etm.2021.10834
MLA
Zhang, Z., Liang, M., Wan, X."Roflumilast, a type of phosphodiesterase 4 inhibitor, can reduce intestinal injury caused by sepsis". Experimental and Therapeutic Medicine 22.6 (2021): 1398.
Chicago
Zhang, Z., Liang, M., Wan, X."Roflumilast, a type of phosphodiesterase 4 inhibitor, can reduce intestinal injury caused by sepsis". Experimental and Therapeutic Medicine 22, no. 6 (2021): 1398. https://doi.org/10.3892/etm.2021.10834
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Z, Liang M and Wan X: Roflumilast, a type of phosphodiesterase 4 inhibitor, can reduce intestinal injury caused by sepsis. Exp Ther Med 22: 1398, 2021.
APA
Zhang, Z., Liang, M., & Wan, X. (2021). Roflumilast, a type of phosphodiesterase 4 inhibitor, can reduce intestinal injury caused by sepsis. Experimental and Therapeutic Medicine, 22, 1398. https://doi.org/10.3892/etm.2021.10834
MLA
Zhang, Z., Liang, M., Wan, X."Roflumilast, a type of phosphodiesterase 4 inhibitor, can reduce intestinal injury caused by sepsis". Experimental and Therapeutic Medicine 22.6 (2021): 1398.
Chicago
Zhang, Z., Liang, M., Wan, X."Roflumilast, a type of phosphodiesterase 4 inhibitor, can reduce intestinal injury caused by sepsis". Experimental and Therapeutic Medicine 22, no. 6 (2021): 1398. https://doi.org/10.3892/etm.2021.10834
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team