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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
2014-January Volume 9 Issue 1

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
2014-January Volume 9 Issue 1

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

Lidocaine protects against renal and hepatic dysfunction in septic rats via downregulation of Toll‑like receptor 4

  • Authors:
    • Jinbo Liu
    • Haohua Zhang
    • Zongcai Qi
    • Xiuying Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China, Department of Anesthesiology, Brain Branch of Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
  • Pages: 118-124
    |
    Published online on: November 14, 2013
       https://doi.org/10.3892/mmr.2013.1799
  • 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

The present study was designed to determine the renoprotective and hepatoprotective effect of lidocaine in septic rats through the Toll‑like receptor 4 (TLR4) signaling pathway. Adult male Sprague‑Dawley rats were randomly divided into the following three groups: control, sepsis model and 10% lidocaine. A model of sepsis was established by injection of lipopolysaccharide (LPS; 5 mg/kg) into the intraperitoneal cavity of rats. The same volume of saline was injected intraperitoneally into rats of the control group instead of LPS. Light microscopy was used to observe structural changes of the hepatic and nephridial tissues. qPCR was used to measure TLR4 mRNA expression levels and the protein expression was detected by flow cytometry. Western blotting was used to measure myocardial nuclear factor κB (NF‑κB) protein levels and ELISA was used to measure the levels of interleukin‑6 (IL‑6) in hepatic and nephridial tissues. The results demonstrated that 10% lidocaine treatment markedly decreased hepatic and nephridial injury in septic rats and inhibited the expression levels of TLR4, NF‑κB and IL‑6, which were upregulated in the sepsis model. In addition, the results indicated that lidocaine protects against renal and hepatic dysfunction in septic rats, which may be mediated by the downregulation of TLR4 and associated signaling molecules and inhibition of the inflammatory response.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Wang H and Ma S: The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome. Am J Emerg Med. 26:711–715. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Dewar DC and Balogh ZJ: The epidemiology of multiple-organ failure: a definition controversy. Acta Anaesthesiol Scand. 55:248–249. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Dinarello CA: Proinflammatory and anti-inflammatory cytokines as mediators in the pathogenesis of septic shock. Chest. 112:S321–S329. 1997. View Article : Google Scholar : PubMed/NCBI

4 

Cohen J: The immunopathogenesis of sepsis. Nature. 420:885–891. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Brun-Buisson C: The epidemiology of the systemic inflammatory response. Intensive Care Med. 26(Suppl 1): S64–S74. 2000. View Article : Google Scholar

6 

Angus DC and Wax RS: Epidemiology of sepsis: an update. Crit Care Med. 29:S109–S116. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Hollmann MW and Durieux ME: Local anesthetics and the inflammatory response: a new therapeutic indication? Anesthesiology. 93:858–875. 2000. View Article : Google Scholar : PubMed/NCBI

8 

Strohm C, Barancik T, Bruhl ML, Kilian SA and Schaper W: Inhibition of the ER-kinase cascade by PD98059 and UO126 counteracts ischemic preconditioning in pig myocardium. J Cardiovasc Pharmacol. 36:218–229. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Das KC and Misra HP: Prevention of reperfusion lung injury by lidocaine in isolated rat lung ventilated with higher oxygen levels. J Postgrad Med. 49:17–20. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Schmid RA, Yamashita M, ando K, Tanaka Y, Cooper JD and Patterson GA: Lidocaine reduces reperfusion injury and neutrophil migration in canine lung allografts. Ann Thorac Surg. 61:949–955. 1996. View Article : Google Scholar : PubMed/NCBI

11 

Tomori H, Shiraishi M, Koga H, et al: Protective effects of lidocaine in hepatic ischemia/reperfusion injury in vitro. Transplant Proc. 30:3740–3742. 1998. View Article : Google Scholar : PubMed/NCBI

12 

Fuentes JM, Talamini MA, Fulton WB, Hanly EJ, Aurora AR and De Maio A: General anesthesia delays the inflammatory response and increases survival for mice with endotoxic shock. Clin Vaccine Immunol. 13:281–288. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Gallos G, Jones DR, Nasr SH, Emala CW and Lee HT: Local anesthetics reduce mortality and protect against renal and hepatic dysfunction in murine septic peritonitis. Anesthesiology. 101:902–911. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Kawai T and Akira S: TLR signaling. Cell Death Differ. 13:816–825. 2006. View Article : Google Scholar

15 

Akira S: TLR signaling. Curr Top Microbiol Immunol. 311:1–16. 2006.

16 

Compton T, Kurt-Jones EA, Boehme KW, et al: Human cytomegalovirus activates inflammatory cytokine responses via CD14 and toll-like receptor 2. J Virol. 77:4588–4596. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Tanimura N, Saitoh S, Matsumoto F, Akashi-Takamura S and Miyake K: Roles for LPS-dependent interaction and relocation of TLR4 and TRAM in TRIF-signaling. Biochem Biophys Res Commun. 368:94–99. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Kawai T and Akira S: The role of pattern-recognition receptors in innate immunity: update on toll-like receptors. Nat Immunol. 11:373–384. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Rittirsch D, Flierl MA and Ward PA: Harmful molecular mechanisms in sepsis. Nat Rev Immunol. 8:776–787. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Akira S and Hemmi H: Recognition of pathogen-associated molecular patterns by TLR family. Immunol Lett. 85:85–95. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Muzio M, Bosisio D, Polentarutti N, et al: Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J Immunol. 164:5998–6004. 2000. View Article : Google Scholar : PubMed/NCBI

22 

O’Neill LAJ and Bowie AG: The family of five: TIR- domain-containing adaptors in toll-like receptor signalling. Nat Rev Immunol. 7:353–364. 2007.

23 

Zhang FX, Kirschning CJ, Mancinelli R, et al: Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes. J Biol Chem. 274:7611–7614. 1999. View Article : Google Scholar

24 

Cario E, Rosenberg IM, Brandwein SL, Beck PL, Reinecker HC and Podolsky DK: Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing toll-like receptors. J Immunol. 164:966–972. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Faure E, Equils O, Sieling PA, et al: Bacterial lipopolysaccharide activates NF-kappaB through toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells. Differential expression of TLR-4 and TLR-2 in endothelial cells. J Biol Chem. 275:11058–11063. 2000. View Article : Google Scholar

26 

Underhill DM, Ozinsky A, Smith KD and Aderem A: Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages. Proc Natl Acad Sci USA. 96:14459–14463. 1999. View Article : Google Scholar : PubMed/NCBI

27 

Ozinsky A, Underhill DM, Fontenot JD, et al: The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci USA. 97:13766–13771. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Poltorak A, He X, Smirnova I, et al: Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science. 282:2085–2088. 1998. View Article : Google Scholar

29 

Ahn KS, Sethi G and Aggarwal BB: Nuclear factor-kappa B: from clone to clinic. Curr Mol Med. 7:619–637. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Lu YC, Yeh WC and Ohashi PS: LPS/TLR4 signal transduction pathway. Cytokine. 42:145–151. 2008. View Article : Google Scholar

31 

Hoffmann A, Natoli G and Ghosh G: Transcriptional regulation via the NF-kappaB signaling module. Oncogene. 25:6706–6716. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Hoffmann A, Levchenko A, Scott ML and Baltimore D: The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation. Science. 298:1241–1245. 2002. View Article : Google Scholar

33 

Couture LA, Piao W, Ru LW, Vogel SN and Toshchakov VY: Targeting toll-like receptor (TLR) signaling by toll/interleukin-1 receptor (TIR) domain-containing adapter protein/MyD88 adapter-like (TIRAP/Mal)-derived decoy peptides. J Biol Chem. 287:24641–24648. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Fitzgerald KA, Palsson-McDermott EM, Bowie AG, et al: Mal (MyD88-adapter-like) is required for toll-like receptor-4 signal transduction. Nature. 413:78–83. 2001. View Article : Google Scholar : PubMed/NCBI

35 

Gray P, Dunne A, Brikos C, Jefferies CA, Doyle SL and O’Neill LA: MyD88 adapter-like (Mal) is phosphorylated by Bruton’s tyrosine kinase during TLR2 and TLR4 signal transduction. J Biol Chem. 281:10489–10495. 2006.PubMed/NCBI

36 

Verstak B, Nagpal K, Bottomley SP, Golenbock DT, Hertzog PJ and Mansell A: MyD88 adapter-like (Mal)/TIRAP interaction with TRAF6 is critical for TLR2- and TLR4-mediated NF-kappaB proinflammatory responses. J Biol Chem. 284:24192–24203. 2009. View Article : Google Scholar : PubMed/NCBI

37 

Brown KL, Cosseau C, Gardy JL and Hancock RE: Complexities of targeting innate immunity to treat infection. Trends Immunol. 28:260–266. 2007. View Article : Google Scholar : PubMed/NCBI

38 

Hoshino K, Takeuchi O, Kawai T, et al: Cutting edge: toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol. 162:3749–3752. 1999.PubMed/NCBI

39 

Arbour NC, Lorenz E, Schutte BC, et al: TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet. 25:187–191. 2000. View Article : Google Scholar : PubMed/NCBI

40 

Johnson GB, Brunn GJ and Platt JL: Cutting edge: an endogenous pathway to systemic inflammatory response syndrome (SIRS)-like reactions through Toll-like receptor 4. J Immunol. 172:20–24. 2004. View Article : Google Scholar : PubMed/NCBI

41 

Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J and Pinsky MR: Epidemiology of severe sepsis in the United States: analysis of incidence, outcome and associated costs of care. Crit Care Med. 29:1303–1310. 2001. View Article : Google Scholar : PubMed/NCBI

42 

Li CY, Tsai CS, Hsu PC, Chueh SH, Wong CS and Ho ST: Lidocaine attenuates monocyte chemoattractant protein-1 production and chemotaxis in human monocytes: possible mechanisms for its effect on inflammation. Anesth Analg. 97:1312–1316. 2003.PubMed/NCBI

43 

Takao Y, Mikawa K, Nishina K, Maekawa N and Obara H: Lidocaine attenuates hyperoxic lung injury in rabbits. Acta Anaesthesiol Scand. 40:318–325. 1996. View Article : Google Scholar : PubMed/NCBI

44 

Sinclair R, Eriksson AS, Gretzer C, Cassuto J and Thomsen P: Inhibitory effects of amide local anaesthetics on stimulus-induced human leukocyte metabolic activation, LTB4 release and IL-1 secretion in vitro. Acta Anaesthesiol Scand. 37:159–165. 1993. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu J, Zhang H, Qi Z and Zheng X: Lidocaine protects against renal and hepatic dysfunction in septic rats via downregulation of Toll‑like receptor 4. Mol Med Rep 9: 118-124, 2014.
APA
Liu, J., Zhang, H., Qi, Z., & Zheng, X. (2014). Lidocaine protects against renal and hepatic dysfunction in septic rats via downregulation of Toll‑like receptor 4. Molecular Medicine Reports, 9, 118-124. https://doi.org/10.3892/mmr.2013.1799
MLA
Liu, J., Zhang, H., Qi, Z., Zheng, X."Lidocaine protects against renal and hepatic dysfunction in septic rats via downregulation of Toll‑like receptor 4". Molecular Medicine Reports 9.1 (2014): 118-124.
Chicago
Liu, J., Zhang, H., Qi, Z., Zheng, X."Lidocaine protects against renal and hepatic dysfunction in septic rats via downregulation of Toll‑like receptor 4". Molecular Medicine Reports 9, no. 1 (2014): 118-124. https://doi.org/10.3892/mmr.2013.1799
Copy and paste a formatted citation
x
Spandidos Publications style
Liu J, Zhang H, Qi Z and Zheng X: Lidocaine protects against renal and hepatic dysfunction in septic rats via downregulation of Toll‑like receptor 4. Mol Med Rep 9: 118-124, 2014.
APA
Liu, J., Zhang, H., Qi, Z., & Zheng, X. (2014). Lidocaine protects against renal and hepatic dysfunction in septic rats via downregulation of Toll‑like receptor 4. Molecular Medicine Reports, 9, 118-124. https://doi.org/10.3892/mmr.2013.1799
MLA
Liu, J., Zhang, H., Qi, Z., Zheng, X."Lidocaine protects against renal and hepatic dysfunction in septic rats via downregulation of Toll‑like receptor 4". Molecular Medicine Reports 9.1 (2014): 118-124.
Chicago
Liu, J., Zhang, H., Qi, Z., Zheng, X."Lidocaine protects against renal and hepatic dysfunction in septic rats via downregulation of Toll‑like receptor 4". Molecular Medicine Reports 9, no. 1 (2014): 118-124. https://doi.org/10.3892/mmr.2013.1799
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