ABSTRACT
PURPOSE: This study evaluates the effects of the gold nanoparticle in endotoxin-induced uveitis in rats. METHODS: Adult male Wistar rats were divided into five groups: saline + saline, lipopolysaccharide (LPS) + saline, LPS + prednisolone, LPS + gold salt (GS) and LPS + gold nanoparticle (GNP). Two hours after LPS administration, prednisolone acetate 1%, GS, and GNP were topically applied to both eyes of rats and repeated every 6 hours for 24 hours. After 24 hours, rats were anesthetized and aqueous humor was sampled and the irides were removed. Aqueous humor TNF-α, myeloperoxidase activity were determined. Irides oxidative damage and content of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) were determined. RESULTS: The administration of LPS-induced eye inflammatory response characterized by an increase in aqueous humor TNF-α, myeloperoxidase, and by irides oxidative damage. All these parameters were decreased by the administration of GNP. Since the inflammatory response secondary to LPS administration depends, in part, to the activation of the TLR4-NF-κB pathway we demonstrated here that a potential mechanism to explain the GNP effects was the decrease on TLR4 content and NF-κB activation. CONCLUSIONS: These findings suggest that topical GNP decreases intraocular inflammation and oxidative damage by interfering in the TLR4-NF-κB pathway.
Subject(s)
Disease Models, Animal , Gold Compounds/pharmacology , Uveitis, Anterior/drug therapy , Administration, Topical , Animals , Aqueous Humor/metabolism , Blotting, Western , Endotoxins , Enzyme-Linked Immunosorbent Assay , Gold Compounds/administration & dosage , Iris/metabolism , Lipopolysaccharides , Male , NF-kappa B/metabolism , Nanoparticles/chemistry , Oxidative Stress/drug effects , Peroxidase/metabolism , Prednisolone/pharmacology , Rats , Rats, Wistar , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/metabolism , Uveitis, Anterior/chemically induced , Uveitis, Anterior/metabolismABSTRACT
BACKGROUND: Contrast-induced nephropathy (CIN) is associated with a combination of hypoxic and toxic renal tubular damage, renal endothelial dysfunction and altered intra-renal microcirculation. Recently, sodium butyrate (SB) has been focused on since it possesses anti-inflammatory activities. Thus, based on the lack of information on the effects of SB in acute kidney injury (AKI), we investigated the possible effects of SB after CIN in rats. METHODS: Wistar rats were divided into three groups: (1 sham) control, (2 MI) AKI treated with contrast medium and (3 MI + SB) AKI plus SB. Six days after contrast administration, blood and kidney were removed for the determination of creatinine, interleukin (IL)-6 levels, oxidative damage parameters and histologic analyses. Nuclear factor kappa B (NF-κB), pIκBα and vasodilator-stimulated phosphoprotein (VASP) protein content were determined by immunoblotting. RESULTS: After 6 days, the levels of creatinine increased significantly in the MI group, and this was attenuated using SB. SB treatment was associated with a decrease on the levels of lipid peroxidation, but not the protein oxidation, and IL-6 levels, as well as tubular damage. These effects are probably mediated, in part, by a decrease on the activation of NF-κB in the kidney, but not alteration in pVASP content. CONCLUSIONS: The current experiment suggests that NF-κB induced an inflammatory response after CIN and SB could inhibit NF-κB expression protecting against CIN in rats.
