Obesity-induced endoplasmatic reticulum (ER) stress has been demonstrated to underlie the induction of obesity-induced JNK and NF-κB activation inflammatory responses, and generation of peripheral insulin resistance. On the other hand, exercise has been used as a crucial tool in obese and diabetic patients, and may reduce inflammatory pathway stimulation. However, the ability of exercise training to reverse endoplasmatic reticulum stress in adipose and hepatic tissue in obesity has not been investigated in the literature. Here, we demonstrate that exercise training ameliorates ER stress and insulin resistance in DIO-induced rats. Rats were fed with standard rodent chow (3,948 kcal kg(-1)) or high-fat diet (5,358 kcal kg(-1)) for 2 months. After that rats were submitted to swimming training (1 h per day, 5 days for week with 5% overload of the body weight for 8 weeks). Samples from epididymal fat and liver were obtained and western blot analysis was performed. Our results showed that swimming protocol reduces pro-inflammatory molecules (JNK, IκB and NF-κB) in adipose and hepatic tissues. In addition, exercise leads to reduction in ER stress, by reducing PERK and eIF2α phosphorylation in these tissues. In parallel, an increase in insulin pathway signaling was observed, as confirmed by increases in IR, IRSs and Akt phosphorylation following exercise training in DIO rats. Thus, results suggest that exercise can reduce ER stress, improving insulin resistance in adipose and hepatic tissue.
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.
Lithium (Li) is the main mood stabilizer and acts on multiple biochemical targets, leading to neuronal plasticity. Several clinical studies have shown that tamoxifen (TMX) - a protein kinase C (PKC) inhibitor - has been effective in treating acute mania. The present study aims to evaluate the effects of TMX on biochemical targets of Li, such as glycogen synthase kinase-3β (GSK-3β), PKC, PKA, CREB, BDNF and NGF, in the brain of rats subjected to an animal model of mania induced by d-amphetamine (d-AMPH). Wistar rats were treated with d-AMPH (2mg/kg, once a day) or saline (Sal; NaCl 0.9%, w/v), Li (47.5 mg/kg, intraperitoneally (i.p.), twice a day) or TMX (1 mg/kg i.p., twice a day) or Sal in protocols of reversion and prevention treatment. Locomotor behavior was assessed using the open-field task, and protein levels were measured by immunoblot. Li and TMX reversed and prevented d-AMPH-induced hyperactivity. Western blot showed that d-AMPH significantly increased GSK-3 and PKC levels, and decreased pGSK-3, PKA, NGF, BDNF and CREB levels in the structures analyzed. Li and TMX were able to prevent and reverse these changes induced by d-AMPH in most structures evaluated. The present study demonstrated that the PKC inhibitor modulates the alterations in the behavior, neurotrophic and apoptosis pathway induced by d-AMPH, reinforcing the need for more studies of PKC as a possible target for treatment of bipolar disorder.
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...
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