Effects of Gold Nanoparticles on Endotoxin-Induced Uveitis in Rats

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 þ saline, lipopolysaccharide (LPS) þ saline, LPS þ prednisolone, LPS þ gold salt (GS) and LPS þ 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-a, myeloperoxidase activity were determined. Irides oxidative damage and content of toll-like receptor 4 (TLR4) and nuclear factor-jB (NF-jB) were determined.RESULTS. The administration of LPS-induced eye inflammatory response characterized by an increase in aqueous humor TNF-a, 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-jB pathway we demonstrated here that a potential mechanism to explain the GNP effects was the decrease on TLR4 content and NF-jB activation.CONCLUSIONS. These findings suggest that topical GNP decreases intraocular inflammation and oxidative damage by interfering in the TLR4-NF-jB pathway. Oxidative stress is also suggested to be pathogenic by inducing inflammation in the eye. 10,11Endotoxin-induced uveitis (EIU) is an established animal model for ocular inflammation. These animals develop acute bilateral anterior inflammation, characterized by a breakdown of the blood-ocular barrier and accumulation of inflammatory cells. 12 Oxidative biomarkers are shown to be elevated in EIU, suggesting that inflammation and oxidative stress cooperatively contribute to its pathogenesis. 13Over the past few decades, gold nanoparticles (GNP) have become the object of special interest due to their antiinflammatory activity.14 Gold compounds have been used as anti-inflammatory treatment against rheumatoid arthritis for more than 50 years. [15][16][17] The molecular mechanisms of gold actions include modulation of pro-inflammatory, as well as inactivation of phagolysosomal enzymes and inhibition of NF-jB. 18,19 In view of these anti-inflammatory properties of gold compounds, the present study investigates the potential applications of GNP in the modulation of the inflammatory response in an animal model of uveitis. MATERIALS AND METHODS GNPs PreparationGNP were prepared as described by Turkevich et al. 20 In brief, glass vials were washed in aqua regia and rinsed in ultrapure water, then aurochloric acid solution (0.2 mM) was gently warmed up to 908C and sodium citrate (39 mM) was added. After 20 minutes of vigorous stirring and refluxing, the solution was cooled at room temperature (20 6 28C) and the GNP were purified by serial centrifugations at 9000g for 10 minutes, followed by supernatant removing and ultra pure water rinsing. The resulting powder was resuspended in s...

Effects of morphine on the expression of cytokines and inflammatory mediators in a rabbit model of endotoxin-induced experimental uveitis

“…In the present study, compared to baseline values, the levels of IL-1 and TNF-α and not of MPO and PGE2 increased after the induction of uveitis; this can be attributed to evaluations being performed during the initial phase of inflammation. The results of the present study corroborate with those of previous studies that have used LPS to induce inflammation (28) and increase levels of TNF-α and IL-1beta. TNF-α, IL-1beta, IL-2, IL-6, and interferon-gamma have also been detected in eyes with idiopathic uveitis.…”

“…The inflammatory process occurs as a tissue response to cell injury (28) initiated by the release of pro-inflammatory agents, particularly IL-1 and TNF-α, which stimulate the production of metabolites and cytokines and the liberation of arachidonic acid, PGs, and leukotrienes (27) . In the present study, compared to baseline values, the levels of IL-1 and TNF-α and not of MPO and PGE2 increased after the induction of uveitis; this can be attributed to evaluations being performed during the initial phase of inflammation.…”

Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats

“…However, in this study, we used a concentration of 70 mg.L -1 , which was shown to be toxic, because the gold levels that accumulate in the organs are proportional to the administered dosage (Lasagna-Reeves et al 2010). Other studies have been conducted using gold nanoparticles for the treatment of certain pathologies in which the NPs were revealed to be non-toxic, likely because they used smaller doses than was used in this current study (Zortea et al 2015;Silveira et al 2014;Dohnert et al 2014;Pereira et al 2012). …”

The splenocyte proliferative response and cytokine secretion in mice after oral administration of commercial gold nanocolloid

“…They retarded the response of human macrophages to IL-1β, and blocked the functions of TLR9 receptor in murine macrophages, decreasing the synthesis of TNF-α, IL-6 and IL-12p40 (Sumbayev et al 2012, Tsai et al 2012). In the in vivo studies, conducted on the animal models of inflammatory diseases, the suppression of macrophage functions by nanogold resulted in decreased levels of pro-inflammatory cytokines and protection from oxidative tissue damage (Tsai et al 2007, Pedersen et al 2009, Pereira et al 2012, Sumbayev et al 2012. The anti-inflammatory effect of the medium AuNPs dose, demonstrated in the present experiment, may have also been a result of the inhibition of inflammatory pathways in resident macrophages, which were certainly present, albeit in small numbers, in cultures of murine splenocytes.…”