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Inhibitory effects of oral disulfiram on endotoxin-induced uveitis in rats.

Abstract：

PURPOSE:Disulfiram (DSF) exhibits a wide variety of biological activities, including an anti-inflammatory action, on which we focused our attention. The aim of the present study was to investigate the effect of oral DSF on endotoxin-induced uveitis (EIU) in rats. METHODS:We investigated its effect upon cellular infiltration and protein leakage, as well as on the concentration of tumor necrosis factor-α (TNF-α), nitric oxide (NO), and prostaglandin E2 (PGE2) in the anterior chamber. Some eyes were enucleated for histologic examination and immunohistochemical analysis. EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). One hour before the LPS injection, either 250, 500, or 750 mg/kg DSF was administered orally. Twenty-four hours later, the aqueous humor was collected from both eyes, and the number of infiltrating cells and protein concentration in the aqueous humor were determined. Levels of TNF-α, NO, and PGE2 were determined by enzyme-linked immunosorbent assay. Immunohistochemical analysis in the iris ciliary body (ICB) cells was performed to determine the expression of activated nuclear factor kappa B (NF-κB), inducible-nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). RESULTS:The oral administration with DSF suppressed, in a dose-dependent manner, the number of inflammatory cells, the protein concentration, and the levels of TNF-α, NO, and PGE2 in the aqueous humor and improved the histiologic status of the ocular tissue. The expression of activated NF-κB-positive cells in the ICB was significantly inhibited by oral administrated with DSF 3 hr after the LPS injection. The LPS-induced increased expressions of iNOS and COX-2 proteins in the ICB were also inhibited by oral DSF 24 hr after LPS injection. CONCLUSIONS:The present results indicate that oral DSF suppresses the inflammation in EIU by inhibiting the NF-κB-dependent pathway and the subsequent production of pro-inflammatory mediators.

journal_name

Curr Eye Res

journal_title

Current eye research

authors

Kanai K,Itoh N,Yoshioka K,Yonezawa T,Ikadai H,Hori Y,Ito Y,Nagai N,Chikazawa S,Hoshi F,Higuchi S

doi

10.3109/02713683.2010.495442

subject

Has Abstract

pub_date

2010-10-01 00:00:00

pages

892-9

issue

eissn

0271-3683

issn

1460-2202

journal_volume

pub_type

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Inhibitory effects of oral disulfiram on endotoxin-induced uveitis in rats.