Abstract
Uveitis, an intraocular inflammatory disease, occurs mostly in young people and can result in the loss of socioeconomic capabilities. Silibinin has been shown to exert anti-inflammatory effects in human retinal pigment epithelial (RPE) cells. The present study investigated the anti-inflammatory effect of silibinin pretreatment on endotoxin-induced uveitis (EIU) in rats and the mechanisms by which it exerts these effects. Uveitis was induced via injection of lipopolysaccharides (LPS) into Lewis rats. Twenty-four hours after the LPS injection, histological examination showed that silibinin decreased inflammatory cell infiltration in the anterior segment of the eyes of LPS-treated rats. Analyses of the aqueous humor showed that silibinin decreased cell infiltration, protein concentration, nitric oxide (NO), and prostaglandin (PG)-E2 production. Western blot analysis indicated that silibinin decreased the expression of inducible NO synthase (iNOS), cyclooxygenase (COX-2), and phosphorylated IkB in the iris-ciliary body (ICB). Immunohistochemistry showed that silibinin decreased intercellular adhesion molecule (ICAM-1) expression in the ICB. In addition, western blot analysis showed that silibinin attenuated the expression of iNOS, COX-2, ICAM-1, and nuclear p65 in LPS-treated RAW cells. In conclusion, silibinin pretreatment prevents EIU and the subsequent production of proinflammatory mediators and ICAM-1, at least in part, by blocking the NF-κB–dependent signaling pathway both in vivo and in vitro. These effects may contribute to the silibinin-mediated preventive effects on intraocular inflammatory diseases such as acute uveitis.
Highlights
Uveitis is an intraocular inflammatory disease that can affect any part of the eye and cause serious complications
We have reported that silibinin effectively suppresses TNF-α and IFN-γ-induced intercellular adhesion molecule (ICAM)-1 expression and synthesis by inhibiting nuclear factor-κB (NF-κB) activity in human retinal pigment epithelial (RPE) cells[23]; to the best of our knowledge, the effects of silibinin on endotoxin-induced uveitis (EIU) and its mechanism of action have not been clearly elucidated
The results of this study show that silibinin significantly attenuated the ocular inflammatory response in rats with EIU, with significant decreases in inflammatory cell infiltration, as well as protein, nitric oxide (NO), and PG-E2 concentrations in the aqueous humor (AqH)
Summary
Uveitis is an intraocular inflammatory disease that can affect any part of the eye and cause serious complications. It accounts for 10–15% of the number of cases of total blindness and up to 20% of the cases of legal blindness in developed countries.[1, 2] It occurs mostly in young people and can result in loss of the patient’s independence and socioeconomic capabilities.[3] Currently, the therapeutic strategy to combat uveitis is to suppress inflammation and corticosteroids are the mainstay of therapy;[4] corticosteroids can cause many unwanted ocular side effects, including accelerated cataract formation, increased intraocular. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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