Skip to main content

Advertisement

SpringerLink
Log in

Liposomal inhibition of acrolein-induced injury in rat cultured urothelial cells

  • Urology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Purpose

To study the protection offered by empty liposomes (LPs) alone against acrolein-induced changes in urothelial cell viability and explored uptake of LPs by primary (rat) urothelial cells.

Methods

Acrolein was used as a means to induce cellular damage and reduce urothelial cellular viability. The effect of acrolein or liposomal treatment on cellular proliferation was studied using 5-bromo-2′-deoxy-uridine assay. Cytokine release was measured after urothelial cells were exposed to acrolein. Temperature-dependent uptake study was carried out for fluorescent-labeled LPs using confocal microscopy.

Results

Liposome pretreatment protected against acrolein-induced decrease in urothelial cell proliferation. LPs also significantly affected the acrolein-induced cytokine (interferon-gamma) release offering protection to the urothelial cells against acrolein damage. We also observed a temperature-dependent urothelial uptake of fluorescent-labeled LPs occurred at 37 °C (but not at 4 °C).

Conclusions

Empty LPs alone provide a therapeutic efficacy against acrolein-induced changes in urothelial cell viability and may be a promising local therapy for bladder diseases. Hence, our preliminary evidence provides support for liposome-therapy for urothelial protection and possible repair.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Stevens JF, Maier CS (2008) Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease. Mol Nutr Food Res 52:7–25

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Nirmal J, Tyagi P, Chancellor MB et al (2013) Development of potential orphan drug therapy of intravesical liposomal tacrolimus for hemorrhagic cystitis due to increased local drug exposure. J Urol 189:1553–1558

    Article  PubMed  CAS  Google Scholar 

  3. Cox PJ (1979) Cyclophosphamide cystitis and bladder cancer. A hypothesis. Eur J Cancer 15:1071–1072

    Article  PubMed  CAS  Google Scholar 

  4. Grinberg-Funes DJ, Sheldon C, Weiss M (1990) The use of prostaglandin F2 alpha for the prophylaxis of cyclophosphamide induced cystitis in rats. J Urol 144:1500–1504

    PubMed  CAS  Google Scholar 

  5. Veerasarn V, Boonnuch W, Kakanaporn C (2006) A phase II study to evaluate WF10 in patients with late hemorrhagic radiation cystitis and prostatitis. Gynecol Oncol 100:179–184

    Article  PubMed  CAS  Google Scholar 

  6. Chuang YC, Lee WC, Lee WC, Chiang PH (2009) Intravesical liposome versus oral pentosan polysulfate for interstitial cystitis/painful bladder syndrome. J Urol 182:1393–1400

    Article  PubMed  CAS  Google Scholar 

  7. Tyagi P, Chancellor M, Yoshimura N, Huang L (2008) Activity of different phospholipids in attenuating hyperactivity in bladder irritation. BJU Int 101:627–632

    Article  PubMed  CAS  Google Scholar 

  8. Fraser MO, Chuang Y, Tyagi P et al (2003) Intravesical liposome administration—a novel treatment for hyperactive bladder in the rat. Urology 61:656–663

    Article  PubMed  Google Scholar 

  9. Federico C, Morittu VM, Britti D et al (2012) Gemcitabine-loaded liposomes: rationale, potentialities and future perspectives. Int J Nanomedicine 7:5423–5436

    PubMed  PubMed Central  Google Scholar 

  10. Chopra B, Barrick SR, Meyers S et al (2005) Expression and function of bradykinin B1 and B2 receptors in normal and inflamed rat urinary bladder urothelium. J Physiol 562:859–871

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Birder L, Andersson KE (2013) Urothelial Signalling. Physiol Rev 93:653–680

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Kashyap M, Kawamorita N, Tyagi V et al (2013) Down-regulation of nerve growth factor expression in the bladder by antisense oligonucleotides as new treatment for overactive bladder. J Urol 190:757–764

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Lazzeri M (2006) The physiological function of the urothelium—more than a simple barrier. Urol Int 76:289–295

    Article  PubMed  Google Scholar 

  14. Teichman JM, Moldwin R (2007) The role of the bladder surface in interstitial cystitis/painful bladder syndrome. Can J Urol 14:3599–3607

    PubMed  Google Scholar 

  15. Parsons CL, Greenberger M, Gabal L et al (1998) The role of urinary potassium in the pathogenesis and diagnosis of interstitial cystitis. J Urol 159:1862–1866

    Article  PubMed  CAS  Google Scholar 

  16. Kuo YC, Kuo HC (2012) Potential factors that can be used to differentiate between interstitial cystitis/painful bladder syndrome and bladder oversensitivity in women. Int J Clin Pract 66:146–151

    Article  PubMed  Google Scholar 

  17. Tang MS, Wang HT, Hu Y et al (2011) Acrolein induced DNA damage, mutagenicity and effect on DNA repair. Mol Nutr Food Res 55:1291–1300

    Article  PubMed  CAS  Google Scholar 

  18. Botteman MF, Pashos CL, Redaelli A et al (2003) The health economics of bladder cancer: a comprehensive review of the published literature. Pharmacoeconomics 21:1315–1330

    Article  PubMed  Google Scholar 

  19. Tyagi P, Hsieh VC, Yoshimura N et al (2009) Instillation of liposomes vs dimethyl sulfoxide or pentosan polysulphate for reducing bladder hyperactivity. BJU Int 104:1689–1692

    Article  PubMed  CAS  Google Scholar 

  20. Yang F, Jin C, Jiang Y et al (2011) Liposome based delivery systems in pancreatic cancer treatment: from bench to bedside. Cancer Treat Rev 37:633–642

    Article  PubMed  CAS  Google Scholar 

  21. Gregoriadis G, Jain S, Papaioannou I et al (2005) Improving the therapeutic efficacy of peptides and proteins: a role for polysialic acids. Int J Pharm 300:125–130

    Article  PubMed  CAS  Google Scholar 

  22. Lee WC, Chuang YC, Lee WC et al (2011) Safety and dose flexibility clinical evaluation of intravesical liposome in patients with interstitial cystitis or painful bladder syndrome. Kaohsiung J Med Sci 27:437–440

    Article  PubMed  CAS  Google Scholar 

  23. Nickel JC, Downey J, Morales A et al (1998) Relative efficacy of various exogenous glycosaminoglycans in providing a bladder surface permeability barrier. J Urol 160:612–614

    Article  PubMed  CAS  Google Scholar 

  24. Penrose HM, Marchelletta RR, Krishnan M et al (2013) Spermidine stimulates T cell protein-tyrosine phosphatase-mediated protection of intestinal epithelial barrier dysfunction. J Biol Chem 288:32651–32662

    Article  PubMed  CAS  Google Scholar 

  25. Smaldone MC, Vodovotz Y, Tyagi V et al (2009) Multiplex analysis of urinary cytokine levels in rat model of cyclophosphamide-induced cystitis. Urology 73:421–426

    Article  PubMed  PubMed Central  Google Scholar 

  26. Baker P, Rye KA, Gamble JR et al (2000) Phospholipid composition of reconstituted high density lipoproteins influences their ability to inhibit endothelial cell adhesion molecule expression. J Lipid Res 41:1261–1267

    PubMed  CAS  Google Scholar 

  27. Williams KJ, Scalia R, Mazany KD et al (2000) Rapid restoration of normal endothelial functions in genetically hyperlipidemic mice by a synthetic mediator of reverse lipid transport. Arterioscler Thromb Vasc Biol 20:1033–1039

    Article  PubMed  CAS  Google Scholar 

  28. Bialecki RA, Tulenko TN, Colucci WS (1991) Cholesterol enrichment increases basal and agonist-stimulated calcium influx in rat vascular smooth muscle cells. J Clin Invest 88:1894–1900

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Soloviev AI, Stefanov AV, Bazilyuk OV et al (1993) Phospholipid vesicles (liposomes) restore endothelium-dependent cholinergic relaxation in thoracic aorta from spontaneously hypertensive rats. J Hypertens 11:623–627

    Article  PubMed  CAS  Google Scholar 

  30. Truschel ST, Ruiz WG, Shulman T et al (1999) Primary uroepithelial cultures. A model system to analyze umbrella cell barrier function. J Biol Chem 274:15020–15029

    Article  PubMed  CAS  Google Scholar 

  31. Nonas S, Miller I, Kawkitinarong K et al (2006) Oxidized phospholipids reduce vascular leak and inflammation in rat model of acute lung injury. Am J Respir Crit Care Med 173:1130–1138

    Article  PubMed  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported in part by NIH grants R37 DK54824 and R01 DK57284 (LAB), R01 DK083323 and a Department of Defense Grant (MBC), grants from the Urology Care Foundation Research Scholars Program and the Allergan Foundation (NJ) and the Kidney Imaging Core of the Pittsburgh Center for Kidney Research (P30-DK079307).

Conflict of interest

The authors declare they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Urology, Oakland University William Beaumont School of Medicine, Rochester, MI, USA

    J. Nirmal & M. B. Chancellor

  2. Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    A. S. Wolf-Johnston

  3. Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    P. Tyagi

  4. Departments of Medicine and Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, A 1217 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA, USA

    L. A. Birder

  5. Lipella Pharmaceuticals Inc., Pittsburgh, PA, USA

    M. Anthony & J. Kaufman

Authors
  1. J. Nirmal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. S. Wolf-Johnston
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. B. Chancellor
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Tyagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Anthony
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Kaufman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L. A. Birder
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. A. Birder.

Additional information

J. Nirmal and A. S. Wolf-Johnston have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nirmal, J., Wolf-Johnston, A.S., Chancellor, M.B. et al. Liposomal inhibition of acrolein-induced injury in rat cultured urothelial cells. Int Urol Nephrol 46, 1947–1952 (2014). https://doi.org/10.1007/s11255-014-0745-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-014-0745-7

Keywords

Search

Navigation