Effects of nanocrystalline silver (NPI 32101) in a rat model of ulcerative colitis.
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)-alpha, interleukin (IL)-1beta, and IL-12, whereas sulfasalazine suppressed MMP-9, IL-1beta, and TNF-alpha, 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-alpha, IL-1beta, 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.
Bhol
Kailash C
KC
NUCRYST Pharmaceuticals Inc., 50 Audubon Road, Wakefield, MA 01880, USA. Kbhol@nucryst.com
Schechter
Paul J
PJ
D000818:Animals; D001557:Benzenesulfonates / Q000633:toxicity; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D005500:Follow-Up Studies; D006241:Haptens; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D012834:Silver / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D001557:Benzenesulfonates; D016207:Cytokines; D006241:Haptens; C007488:dinitrobenzenesulfonic acid; D012834:Silver; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9