Document Detail

Immunosuppressive and anti-inflammatory action of antioxidants in rat autoimmune diabetes.
MedLine Citation:
PMID:  15120750     Owner:  NLM     Status:  MEDLINE    
Oxidative stress makes an important contribution to the development of autoimmune diabetes. We therefore tested the possible therapeutic value of two anti-oxidants, butylated hydroxyanisole (BHA) and pyrrolidine dithiocarbamate (PDTC), in the animal model of diabetes induced in susceptible DA rats by multiple low doses of streptozotocin (MLD-SZ, 20 mg/kg/day for 5 days). Administration of either BHA, or PDTC (50 mg/kg/day for 7 days), after finishing MLD-SZ injections, attenuated both the development of hyperglycemia and insulitis. Ex vivo analysis revealed that BHA treatment reduced the proliferation of autoreactive lymphocytes and down-regulated their adhesion to endothelium. In addition, BHA markedly attenuated the production of proinflammatory cytokines IL-1beta and TNF-alpha by both islets of pancreas and peritoneal macrophages. In parallel, macrophage release of cytotoxic oxygen and nitrogen intermediates superoxide anion (O(2)*(-)) and nitric oxide (NO*), respectively, was significantly inhibited. Finally, BHA treatment reduced intrapancreatic expression of inducible NO synthase (iNOS) and consequent production of NO* by pancreatic islets. Together, these data indicate that antioxidant agents might be a feasible therapeutic tools to interfere with development of autoimmune diabetes at multiple levels, including lymphocyte proliferation and adhesion, as well as the production of proinflammatory and cytotoxic mediators.
Stanislava D Stosic-Grujicic; Djordje M Miljkovic; Ivana D Cvetkovic; Danijela D Maksimovic-Ivanic; Vladimir Trajkovic
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of autoimmunity     Volume:  22     ISSN:  0896-8411     ISO Abbreviation:  J. Autoimmun.     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-05-03     Completed Date:  2004-12-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8812164     Medline TA:  J Autoimmun     Country:  England    
Other Details:
Languages:  eng     Pagination:  267-76     Citation Subset:  IM    
Laboratory of Immunology, Institute for Biological Research Sinisa Stankovic, 29 Novembra 142, 11000 Belgrade, Yugoslavia. duta@eunet.yu
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MeSH Terms
Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
Antioxidants / therapeutic use*
Autoimmunity / drug effects
Butylated Hydroxyanisole / therapeutic use
Diabetes Mellitus, Experimental / drug therapy*,  immunology,  metabolism,  pathology
Diabetes Mellitus, Type 1 / drug therapy*,  immunology,  metabolism,  pathology
Immunosuppressive Agents / therapeutic use
Interleukin-1 / biosynthesis
Islets of Langerhans / drug effects,  immunology,  pathology
Lymphocytes / drug effects,  immunology
Nitric Oxide / biosynthesis
Nitric Oxide Synthase / metabolism
Nitric Oxide Synthase Type II
Pyrrolidines / therapeutic use
Rats, Inbred Strains
Superoxides / metabolism
Thiocarbamates / therapeutic use
Tumor Necrosis Factor-alpha / biosynthesis
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Antioxidants; 0/Immunosuppressive Agents; 0/Interleukin-1; 0/Pyrrolidines; 0/Thiocarbamates; 0/Tumor Necrosis Factor-alpha; 10102-43-9/Nitric Oxide; 11062-77-4/Superoxides; 25013-16-5/Butylated Hydroxyanisole; 25769-03-3/pyrrolidine dithiocarbamic acid; EC Oxide Synthase; EC Oxide Synthase Type II; EC protein, rat

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