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...

This study aimed to compare the effects of three different resistance exercise models on the quadriceps muscle crosssectional area, as well as on mTOR phosphorylation and other pivotal molecules involved in the upstream regulation of mTOR.Twenty-four male Wistar rats were divided into untrained (control), endurance resistance training, strength resistance training, and hypertrophy resistance training (HRT) groups (n=6). After 12 weeks of training, the red portion of the quadriceps was removed for histological and Western blot analyses. The results showed that the quadriceps weight and cross-sectional areas in the exercised groups were higher than those of the untrained rats. However, the HRT group presented better results than the other two experimental groups. This same pattern was observed for mTOR phosphorylation and for the most pivotal molecules involved in the upstream control of mTOR (increase of PKB, 14-3-3, ERK, p38 MAPK, and 4E-BP1 phosphorylation, and reduction of tuberin, sestrin 2, REDD1, and phospho AMPK). In summary, our study showed that HRT leads to high levels of mTOR phosphorylation as well as of other proteins involved in the upstream regulation of mTOR.

Our results demonstrate that the inhibition of SREBP-1c decreased the expression of lipogenic enzymes, reducing the accumulation of triglycerides and, finally, reversing hepatic steatosis in mice.

Problem. There was no direct correlation between plasma and placental oxidative damage parameters and inflammation and evidence of TLR4 pathway activation in the placenta in preeclamptic (PE) patients. Method of Study. 33 PE patients and 33 normotensive pregnant women were included. The maternal section of the placenta and blood were collected to the determination of oxidative damage markers (thiobarbituric acid reactive species and protein carbonyls), inflammatory response (interleukin-6 and myeloperoxidase activity), and activation of the TLR-4-NF-kB pathway. Results. An increase of IL-6 levels in both plasma and placenta was observed, but myeloperoxidase activity was not significantly different comparing the groups. Oxidative damage parameters were increased in plasma and placenta in PE patients. A significant increase of the protein levels of TLR-4 and NF-kB was observed in the placenta. Conclusion. The TLR4-NF-kB pathway is upregulated in PE, probably generating local and systemic inflammatory response that is followed by local and systemic oxidative damage.

Our results indicate that ROS induced by acute exercise play the important role of activating eNOS, a process apparently mediated by Akt and AMPK.