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Immunosuppressive and anti-inflammatory action of antioxidants in rat autoimmune diabetes.

Abstract：

: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.

journal_name

J Autoimmun

journal_title

Journal of autoimmunity

authors

Stosic-Grujicic SD,Miljkovic DM,Cvetkovic ID,Maksimovic-Ivanic DD,Trajkovic V

doi

10.1016/j.jaut.2004.01.005

subject

Has Abstract

pub_date

2004-06-01 00:00:00

pages

267-76

issue

4

eissn

0896-8411

issn

1095-9157

pii

S089684110400006X

journal_volume

22

pub_type

杂志文章

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