Pentoxifylline (PTX) attenuates LPS-induced acute liver injury via effects on ICAM-1 expression

pcij picture in post
Pathophysiology of Cell Injury Journal  Volume 5, Issue 1, pages 26-39
Received November 11, 2015; accepted April 12, 2016; published June 19, 2016

 Jia-bo Wang,Trisha Dezube, Margaret M. Kearney, Krishne MacLean*



Sepsis is characterized by up-regulation of inflammatory mediators in different pathways. Phosphodiesterase enzymes are often targets for many pharmacological inhibitions which can prolong or activate the effects of physiological processes that mediated by cAMP or cGMP through inhibition of their degradation. We hypothesized that Pentoxifylline (PTX) treatment in sepsis model down-regulates the inflammatory response and may decrease liver injury. Wild type mice were randomized into three groups: Sham, LPS (5 mg/kg i.v.), and PTX + LPS (25 mg/kg i.v., injection). Following 4-hour of endotoxemia, we analysis plasma for liver enzymes, liver tissue for histology (H&E) and immunohistochemistry, in addition to evaluated intercellular adhesion molecule 1 (ICAM-1) by electrophoretic mobility shift assay. Pentoxifylline (PTX) has been shown to down-regulated both ICAM-1 and pro-inflammatroy cytokine effects on lipopolysaccharide (LPS) induced liver injury. Further studies of endotoxemia are needed to ascertain the benefit of PTX as liver protection agent.

Keywords: Phosphodiesterase; Sepsis; LPS; Pentoxifylline

Article citationReferencesFull-Text/PDFFeedback
The citation data is computed by the crosssref service:



1. Coca SG, Yusuf B, Shlipak MG, Garg AX, Parikh CR. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. American journal of kidney diseases. 2009;53(6):961-73. [PubMed]

2. Mehta RL, Pascual MT, Soroko S, et al. Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney international 2004;66(4):1613-21. [PubMed]

3. Dinarello C, Arend,W, Sims J, et al. IL-1 family nomenclature. Nat. Immunol 2010;11:973. [Abstract/Full-Text]

4. Jacob DH, Zeng IU, Tsung Y, et al. Tpl2 exaggerated ischemic hepatic injury through induction of apoptosis: Downstream of caspase-9. American Journal of BioMedicine 2014;2(4):422–439. [Abstract/Full-Text]

5. Hsu CY, McCulloch CE, Fan D, Ordonez JD, Chertow GM, Go AS. Community-based incidence of acute renal failure. Kidney Int 2007;72(2):208-212. [Abstract/Full-Text]

6. Lameire N, Van Biesen W, Vanholder R. Acute renal failure. Lancet 2005;365:417-430. [Abstract/Full-Text]

7. American Society of Nephrology Renal Research Report. J Am Soc Nephrol 2005;16:1886-19063. [PubMed]

8. Towne J, Sims J. IL-36 in psoriasis. Curr Opin Pharmacol 2012;12(4):486-90. [PubMed]

9. Obialo CI, Okonofua EC, Tayade AS, et al. Epidemiology of de novo acute renal failure in hospitalized African Americans: comparing community-acquired vs hospital-acquired disease. Arch Intern Med 2000;160:1309-1313. [PubMed]

10. Chertow GM, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 2005;16:3365-3370. [PubMed]

11. Hou SH, Bushinsky DA, Wish JB, Cohen JJ, Harrington JT. Hospital-acquired renal insufficiency: A prospective study. Am J Med 1983;74:243 -248. [PubMed]

12. Dagher PC, Herget-Rosenthal S, et al. Newly developed techniques to study and diagnose acute renal failure. J Am Soc Nephrol 2003;14:2188 -2198. [PubMed]

13. Smith GL, Vaccarino V, Kosiborod M, et al. Worsening renal function: What is a clinically meaningful change in creatinine during hospitalization with heart failure? J Card Fail 2003;9:13-25. [PubMed] 

14. Agarwal A, Nick HS. Renal response to tissue injury: lessons from heme oxygenase-1 GeneAblation and expression. J Am Soc Nephrol 2000;11(5):965-73. [PubMed]

15. Paller MS. Hemoglobin- and myoglobin-induced acute renal failure in rats: role of iron in nephrotoxicity. The American journal of physiology 1988;255(3 Pt 2):F539-44 [PubMed]

16.Kezic A, Thaiss F, Becker JU, Tsui TY, Bajcetic M. Effects of everolimus on oxidative stress in kidney model of ischemia/reperfusion injury. American journal of nephrology 2013;37(4):291-301. [PubMed] 

17. Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005;294:813–818. [PubMed]

18. Gabay C, Towne JE. Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions. J Leukoc Biol 2015;97(4):645-52. [Abstract/Full-Text]

19. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 2005;16(11):3365-3370. [PubMed]

20. Vigne S, Palmer G, Lamacchia C, et al. IL-36R ligands are potent regulators of dendritic and T cells. Blood 2011;118:5813-5823. [PubMed]

21. Lamacchia C, Palmer G, Rodriguez E, Martin P, Vigne S, et al. The severity of experimental arthritis is independent of IL-36 receptor signaling. Arthritis Res Ther 2013;15:R38. [PubMed]

22. Pan G, Risser P, Mao W, et al. IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL-1Rrp. Cytokine 2001;13:1-7. [PubMed]

23. Schmitz J, Owyang A, Oldham E, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 2005;23:479-490. [Abstract/Full-Text]


1. Access this article  through your login credentials or your institution

Get Access

2. Access this article through OpenAthens/Sign in

3. Purchase this article at rate $55.00 and received Full-Text/PDF
You will have online immediate access to article following the completion of this purchase and you may download and print a copy of each article for your personal use. Use the coding below to purchase your article as PDF by credit card, debit card, payball will be asked to supply your billing card information. Before continue with your purchase please read carefully BM–Publisher terms and conditions of purchase.

Purchase Article

 For any technique error please contact us and will be response to sending purchase article by email.

Thank you for visiting Pathophysiology of Cell Injury Journal.  * = Required fields

[contact-form-7 404 "Not Found"]

Print Friendly, PDF & Email