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Kouichi Ohta, Kohzo Nakayama, Toru Kurokawa, Takanobu Kikuchi, Nagahisa Yoshimura; Inhibitory Effects of Pyrrolidine Dithiocarbamate on Endotoxin-Induced Uveitis in Lewis Rats. Invest. Ophthalmol. Vis. Sci. 2002;43(3):744-750.
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purpose. To determine the effect of pyrrolidine dithiocarbamate (PDTC), an
antioxidant nuclear factor (NF)-κB inhibitor, on the ocular
inflammation induced by lipopolysaccharide (LPS).
methods. Endotoxin-induced uveitis (EIU) was produced by a footpad injection of
200 μg LPS in male Lewis rats. PDTC (200 mg/kg) was injected
intraperitoneally 30 minutes before the LPS administration. The number
of infiltrating cells and protein concentration in the aqueous humor
(AqH) was determined from the AqH collected at 24 hours.
Immunohistochemical staining with a monoclonal antibody against
activated NF-κB was performed to evaluate the effect of PDTC on
NF-κB activation. Interleukin (IL)-1β, IL-6, and tumor necrosis
factor (TNF)-α mRNA expression in the iris-ciliary body (ICB) was
determined by RNase protection assay (RPA). The levels of these
cytokines and nitric oxide (NO) production were also determined.
results. The number of cells in the AqH was 1100 ± 254 cells/μL in rats
injected with LPS and 90 ± 43 cells/μL in rats pretreated with
PDTC (P < 0.001). The concentration of proteins
was significantly lower in the AqH of rats pretreated with PDTC than in
those without PDTC. The number of activated NF-κB–positive cells in
the ICB was reduced by the PDTC treatment. The ICB at 6 hours after LPS
injection exhibited increased expression of IL-1β, IL-6, and TNF-α
mRNAs, which was decreased after PDTC pretreatment. PDTC also
significantly diminished the levels of these cytokines and
nitrite-nitrate in the AqH.
conclusions. These results suggest that PDTC reduces ocular inflammation in eyes
with EIU by downregulating proinflammatory cytokine expression and by
inhibiting the NF-κB–dependent signaling
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