Skip to main content

Advertisement

Log in

Effects of Nanocrystalline Silver (NPI 32101) in a Rat Model of Ulcerative Colitis

  • Original Paper
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Nanocrystalline silver (NPI 32101) has been demonstrated to have antimicrobial and anti-inflammatory properties. The purpose of this study was to assess the effect of NPI 32101 in a rat model of ulcerative colitis and the possible mechanisms of action of the effects observed. NPI 32101, 4 mg/kg intracolonically or 40 mg/kg orally, significantly reduced colonic inflammation compared to the placebo and no-treatment groups. Sulfasalazine (100 mg/kg), either intracolonically or orally, also reduced colonic inflammation. NPI 32101 significantly suppressed the expression of matrix metalloproteinase (MMP)-9, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-12, whereas sulfasalazine suppressed MMP-9, IL-1β, and TNF-α, but not IL-12, compared to placebo. MMP-9 activity was reduced by NPI 32101 and sulfasalazine. NPI 32101 administered intracolonically or orally decreases ulcerative colitis in a rat model and is as effective as sulfasalazine. NPI 32101 treatment suppresses the expression and activity of MMP-9 and the expression of TNF-α, IL-1β, and IL-12, mechanisms by which NPI 32101 may exert its anti-inflammatory effects. NPI 32101 may have therapeutic potential for treatment of ulcerative colitis.

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

Access this article

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Podolsky DK (2002) Inflammatory bowel disease. N Eng J Med 347:417–429

    Article  CAS  Google Scholar 

  2. Louis E (2001) The immuno-inflammatory reaction in Crohn’s disease and ulcerative colitis: characterization, genetics and clinical application: focus on TNF-alpha. Acta Gastroenterol 64:1–5

    CAS  Google Scholar 

  3. Reinecker HC, Steffen M, Witthoeft T, Pflueger I, Schreiber S, MacDermott RP (1993) Enhanced secretion of TNF-alpha, IL-6, and IL-1 by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn’s disease. Clin Exp Immunol 94:174–181

    Article  PubMed  CAS  Google Scholar 

  4. Monteleone G, Biancone L, Marasco R, Morrone G, Marasco O, Luzza F, Pallone F (1997) Interleukin-12 is expressed and actively released by Crohn’s disease intestinal lamina propria mononuclear cells. Gastroenterology 112:1169–1178

    Article  PubMed  CAS  Google Scholar 

  5. Bauditz J, Wedel S, Lochs H (2002) Thalidomide reduces tumor necrosis factor alpha and interleukin-12 production in patients with chronic active Crohn’s disease. Gut 50:196–200

    Article  PubMed  CAS  Google Scholar 

  6. Seegers D, Bouna G, Pena AS (2002) A critical approach to new forms of treatments of Crohns diseases and ulcerative colitis. Aliment Pharmacol 16:53–58

    Article  Google Scholar 

  7. Ogata H, Hibi T (2003) Cytokine and anti-cytokine therapies for inflammatory bowel diseases. Curr Pharm Des 14:1107–1113

    Article  Google Scholar 

  8. Schmidt C, Marth T, Wittig BM (2002) Interleukin-12 antagonists as new therapeutic agents in inflammatory bowel disease. Pathobiology 70:177–183

    Article  PubMed  CAS  Google Scholar 

  9. Su C, Salazberg BA, Lewis JD, Deren JJ, Kornbluth A, Katzka DA, Stein RB, Adler DR, Lichtenstein GR (2002) Efficacy of anti-tumor necrosis factor therapy in patients with ulcerative colitis. Am J Gastroenterol 97:2577–2584

    Article  PubMed  CAS  Google Scholar 

  10. Yin H Q, Langford R, Burrell RE (1999) Comparative evaluation of the antimicrobial activity of Acticoat antimicrobial dressing. J Burn Care Rehab 20:195–200

    Article  CAS  Google Scholar 

  11. Bhol KC, Alroy J, Schechter PJ (2004) Anti-inflammatory effect of topical nanocrystalline silver cream on allergic contact dermatitis in a guinea pig model. Clin Exp Dermatol 29:282–287

    Article  PubMed  CAS  Google Scholar 

  12. Bhol KC, Schechter PJ (2005) Topical nanocrystalline silver cream suppresses inflammatory cytokines and induces apoptosis of inflammatory cells in a murine model of allergic contact dermatitis. Br J Dermatol 152:1235–1242

    Article  PubMed  CAS  Google Scholar 

  13. Bhol K C, Schechter PJ (2005) Topical nanocrystalline silver cream inhibits expression of MMP-9 in animal models of allergic contact dermatitis. J Invest Dermatol (Suppl) 124:A117

    Google Scholar 

  14. Castaneda FE, Walia B, Kumar MV, Patel NR, Roser S, Kolachala L, Rojas M, Wang L, Opera G, Garg P, Gewirtz AT, Roman J, Merlin D, Sitaraman SV (2005) Targeted deletion of Metalloproteinase 9 attenuates experimental colitis in mice: central role of epithelial derived MMP. Gastroenterology 129:1991–2008

    Article  PubMed  CAS  Google Scholar 

  15. Marco RD, Mangano K, Quattrocchi C, Musumeci R, Speciale AM, Papaccio G, Buschard K, Bendtzen K, Nicoletti F (2003) Curative effects of sodium fusidate on the development of dinitrobenzenesulfonic acid-induced colitis in rats. Clin Immunol 109:266–271

    Article  PubMed  CAS  Google Scholar 

  16. Cuzzocrea S, McDonald MC, Mazzon E, Mota-Filipe H, Centorrino T, Terranova ML, Ciccolo A, Britti D, Caputi AP, Thiemermann C (2001) Calpain inhibitor 1 reduces colon injury caused by dinitrobenzene sulphonic acid in the rat. Gut 48:478–488

    Article  PubMed  CAS  Google Scholar 

  17. Kim YS, Son M, Ko JI, Cho H, Yoo M, Kim WB, Song SI, Kim CY (1999) Effect of DA-6034 a derivative of Flanoid on experimental animal model of inflammatory bowel diseases. Arch Pharm Res 22:354–360

    Article  PubMed  CAS  Google Scholar 

  18. Morris GP, Beck PL, Herridge MS, Depew WT, Szewezuk MR, Wallace JL (1989) Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96:795–803

    PubMed  CAS  Google Scholar 

  19. Luke H H, Ko JKS, Fung HS, Cho CH (2002) Delineation of the protective action of zinc sulfate on ulcerative colitis. Eur J Pharmacol 443:197–204

    Article  Google Scholar 

  20. Wallace JL, MacNaughton WK, Morris GP, Beck PL (1989) Inhibition of leukotrine synthesis markedly accelerate healing in a rat model of inflammatory bowel disease. Gastroenterology 96:29–36

    PubMed  CAS  Google Scholar 

  21. Griffiths CEM, Barker JNWN, Kunkel S, Nickoloff BJ (1991) Modulation of leukocyte adhesion molecules, a T-cell chemotaxin (IL-8) and a regulatory cytokine (TNF-a) in allergic contact dermatitis (rhus dermatitis). Br J Dermatol 124:519–526

    Article  PubMed  CAS  Google Scholar 

  22. Hawkins JV, Emmel EL, Feuer JJ (1997) Protease activity in a hapten-induced model of ulcerative colitis in rats. Dig Dis Sci 42:1969–1980

    Article  PubMed  CAS  Google Scholar 

  23. Medina C, Videla S, Radomski A, Radomski MW, Antollin M, Guarner F, Vilaseca J, Salas A, Malagelada JR (2003) Increased activity and expression of matrix metalloproteinase-9 in a rat model of distal colitis. Am J Physiol Gastrointest Liver Physiol 284:G116–G122

    PubMed  CAS  Google Scholar 

  24. Hanauer SB, Present DH (2003) The state of the art in the management of inflammatory bowel disease. Rev Gastroenterol Disord 3:81–92

    PubMed  Google Scholar 

  25. Doering J, Begue B, Lentze MJ (2004) Induction of T lymphocyte apoptosis by sulfasalazine in patients with Crohn’s disease. Gut 53:1632–1638

    Article  PubMed  CAS  Google Scholar 

  26. Azad Khan AK, Truelove SC, Aronseq JK (1982) The disposition and metabolism of sulfasalazine (salicylazosulfapyridine) in man. Br J Clin Pharmacol 13:523–528

    CAS  Google Scholar 

  27. Bertevello PL, Logullo AF, Fabio SN, Campos FM, Chiferi V, Alves CC, Torrinhas RS, Gama-Rodrigues JJ, Waitzberg DL (2005) Immunohistochemical assessment of mucosal cytokine profile in acetic acid experimental colitis. Clinics 60:277–286

    Article  PubMed  Google Scholar 

  28. Sartor RB (1994) Cytokines in intestinal inflammation: pathophysiological and clinical considerations. Gastroenterology 106:533–536

    PubMed  CAS  Google Scholar 

  29. Blam ME, Stein RBS, Lichtenstein GR (2001) Integrating anti-tumor necrosis factor therapy in inflammatory bowel disease: current and future perspectives. Am J Gastroenterol 96:1977–1997

    PubMed  CAS  Google Scholar 

  30. Rogler G, Andus T (1998) Cytokines in inflammatory bowel disease. World J Surg 22:382–389

    Article  PubMed  CAS  Google Scholar 

  31. Neurath MF, Fuss I, Kelsall BL, Stuber E, Strober W (1995) Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med 182:1281–1290

    Article  PubMed  CAS  Google Scholar 

  32. Krane SM (1994) Clinical importance of matrix metalloproteinase and their inhibitors. Ann NY Acad Sci 732:1–10

    Article  PubMed  CAS  Google Scholar 

  33. von Lampe B, Barthel B, Coupland SE, Riecken EO, Rosewicz S (2000) Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel diseases. Gut 47:63–73

    Article  PubMed  CAS  Google Scholar 

  34. Seifert WF, Wobbes T, Hendriks T (1996) Divergent patterns of matrix metalloproteinase activity during wound healing in ileum and colon of rats. Gut 39:114–119

    PubMed  CAS  Google Scholar 

  35. Wright BJ, Lam K, Burrell AG, Olson ME, Burrell RE (2002) Early healing events in a porcine model of contaminated wounds: effect of nanocrystalline silver on matrix metalloproteinases, cell apoptosis and healing. Wound Rep Reg 10:141–151

    Article  Google Scholar 

Download references

Acknowledgments

The authors thank Michael Hirsch and Diksha Bhatia for their technical assistance. This work was supported by NUCRYST Pharmaceuticals Inc.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kailash C. Bhol.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bhol, K.C., Schechter, P.J. Effects of Nanocrystalline Silver (NPI 32101) in a Rat Model of Ulcerative Colitis. Dig Dis Sci 52, 2732–2742 (2007). https://doi.org/10.1007/s10620-006-9738-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-006-9738-4

Keywords

Navigation