Role of Oxidative Stress on Insulin Resistance in Diet-Induced Obesity Mice.

Insulin resistance is the link between obesity and type 2 diabetes mellitus. The molecular mechanism by which obese individuals develop insulin resistance has not yet been fully elucidated; however, inconclusive and contradictory studies have shown that oxidative stress may be involved in the process. Thus, this study aimed to evaluate the effect of reactive species on the mechanism of insulin resistance in diet-induced obese mice. Obese insulin-resistant mice were treated with N-acetylcysteine (NAC; 50 mg/kg per day, for 15 days) by means of oral gavage. Twenty-four hours after the last NAC administration, the animals were euthanized and their tissues were extracted for biochemical and molecular analyses. NAC supplementation induced improved insulin resistance and fasting glycemia, without modifications in food intake, body weight, and adiposity. Obese mice showed increased dichlorofluorescein (DCF) oxidation, reduced catalase (CAT) activity, and reduced glutathione levels (GSH). However, treatment with NAC increased GSH and CAT activity and reduced DCF oxidation. The gastrocnemius muscle of obese mice showed an increase in nuclear factor kappa B (NFκB) and protein tyrosine phosphatase (PTP1B) levels, as well as c-Jun N-terminal kinase (JNK) phosphorylation compared to the control group; however, NAC treatment reversed these changes. Considering the molecules involved in insulin signaling, there was a reduction in insulin receptor substrate (IRS) and protein kinase B (Akt) phosphorylation. However, NAC administration increased IRS and Akt phosphorylation and IRS/PI3k (phosphoinositide 3-kinase) association. The results demonstrated that oxidative stress-associated obesity could be a mechanism involved in insulin resistance, at least in this animal model.

Effects of Avocado Oil Supplementation on Insulin Sensitivity, Cognition, and Inflammatory and Oxidative Stress Markers in Different Tissues of Diet-Induced Obese Mice.

Obesity induces insulin resistance, chronic inflammation, oxidative stress, and neurocognitive impairment. Avocado oil (AO) has antioxidants and anti-inflammatory effects. This study evaluated the effect of AO supplementation on obese mice in the adipose tissue, muscle, liver, and hippocampus. Male C57BL/6J mice received a standard and high-fat diet (20 weeks) and then were supplemented with AO (4 mL/kg of body weight, 90 days) and divided into the following groups: control (control), control + avocado oil (control + AO), diet-induced obesity (DIO), and diet-induced obesity + avocado oil (DIO + AO) (n = 10/group). AO supplementation was found to improve insulin sensitivity and decrease hepatic fat accumulation and serum triglyceride levels in DIO mice. AO improved cognitive performance and did not affect mood parameters. Oxidative marker levels were decreased in DIO + AO mice in all the tissues and were concomitant with increased catalase and superoxide dismutase activities in the epididymal adipose tissue and quadriceps, as well as increased catalase activity in the liver. AO in obese animals further induced reductions in TNF-α and IL-1ß expressions in the epididymal adipose tissue and quadriceps. These results suggest that AO supplementation has the potential to be an effective strategy for combating the effects of obesity in rats, and human studies are needed to confirm these findings.

Effects of Zingiber officinale extract supplementation on metabolic and genotoxic parameters in diet-induced obesity in mice.

Obesity is an epidemic associated with many diseases. The nutraceutical Zingiber officinale (ZO) is a potential treatment for obesity; however, the molecular effects are unknown. Swiss male mice were fed a high-fat diet (59 % energy from fat) for 16 weeks to generate a diet-induced obesity (DIO) model and then divided into the following groups: standard diet + vehicle; standard diet + ZO; DIO + vehicle and DIO + ZO. Those in the ZO groups were supplemented with 400 mg/kg per d of ZO extract (oral administration) for 35 d. The animals were euthanised, and blood, quadriceps, epididymal fat pad and hepatic tissue were collected. DIO induced insulin resistance, proinflammatory cytokines, oxidative stress and DNA damage in different tissues. Treatment with ZO improved insulin sensitivity as well as decreased serum TAG, without changes in body weight or adiposity index. TNF-α and IL-1ß levels were lower in the liver and quadriceps in the DIO + ZO group compared with the DIO group. ZO treatment reduced the reactive species and oxidative damage to proteins, lipids and DNA in blood and liver in obese animals. The endogenous antioxidant activity was higher in the quadriceps of DIO + ZO. These results in the rat model of DIO may indicate ZO as an adjuvant on obesity treatment.

Fish oil reduces subclinical inflammation, insulin resistance, and atherogenic factors in overweight/obese type 2 diabetes mellitus patients: A pre-post pilot study.

OBJECTIVE: Insulin resistance-associated obesity and type 2 diabetes mellitus (T2DM) are commonly accompanied with metabolic lipid abnormalities and are characterized by hypertriglyceridemia and low HDL-c levels (atherogenic index plasma, AIP). The primary molecular mechanism that is known to cause insulin resistance is chronic low-grade inflammation. Considering that omega-3 fatty acid reduces subclinical inflammation, we hypothesized that fish oil could affect insulin resistance and AIP. Therefore, the present study evaluated the effects of fish oil supplementation on the inflammatory, insulin resistance, and atherogenic factors in overweight/obese T2DM patients. RESEARCH DESIGNS AND METHODS: In this study, we recruited 32 overweight and/or obese patients diagnosed with T2DM for over one year and who exhibited hypertriglyceridemia. These patients received fish oil supplementation (4.0 g/day) for eight weeks. Anthropometric and body composition measurements were obtained. In addition, blood samples were collected before and after omega-3 supplementation for the evaluation of lipid profile, glycemia, insulin, and inflammation. RESULTS: As expected, patients showed reduction in the TNFα, IL-1ß, and Il-6 levels after fish oil supplementation and showed improved insulin sensitivity (HOMA-IR) without observed alterations in anthropometric and body composition. These observations were followed by reduction in the levels of triglycerides and non-esterified fatty acids, increase in HDL cholesterol levels, and a significant reduction in triglycerides/HDL-c ratio, and total cholesterol/HDL-c ratio. CONCLUSION: Fish oil supplementation is effective in reducing the levels of proinflammatory cytokines, improving insulin resistance, and reducing atherogenic factors in overweight/obese and T2DM patients independent of weight loss.

Cigarette smoke exposure induces ROS-mediated autophagy by regulating sestrin, AMPK, and mTOR level in mice.

Many pathological conditions linked to cigarette smoking are caused by the production of reactive oxygen species (ROS). The present study was conducted to analyze the effect of ROS on the lungs of Swiss mice exposed to cigarette smoking, focusing on autophagy-mediated mechanisms, and investigate the involvement of SESN2, AMPK, and mTOR signaling. Mice were exposed to cigarette smoke (CS) for 7, 15, 30, 45, and 60 days; the control group was not exposed to CS. Only mice exposed to CS for 45 days were selected for subsequent N-acetylcysteine (NAC) supplementation and smoke cessation analyses. Exposure to CS increased the production of ROS and induced molecular changes in the autophagy pathway, including an increase in phosphorylated AMPK and ULK1, reduction in phosphorylated mTOR, and increases in SESN2, ATG12, and LC3B levels. NAC supplementation reduced ROS levels and reversed all molecular changes observed upon CS treatment, suggesting the involvement of oxidative stress in inducing autophagy upon CS exposure. When exposure to CS was stopped, there were decreases in the levels of oxidative stress, AMPK and ULK1 phosphorylation, and autophagy-initiating molecules and increase in mTOR phosphorylation. In conclusion, these results suggest the involvement of ROS, SESN2, AMPK, and mTOR in the CS-induced autophagic process in the lung.

Strength training and aerobic exercise alter mitochondrial parameters in brown adipose tissue and equally reduce body adiposity in aged rats.

With aging, there is a reduction in mitochondrial activity, and several changes occur in the body composition, including increased adiposity. The dysfunction of mitochondrial activity causes changes and adaptations in tissue catabolic characteristics. Among them, we can mention brown adipose tissue (BAT). BAT's main function is lipid oxidation for heat production, hence playing a role in adaptive thermogenesis induced by environmental factors such as exercise. It is known that exercise causes a series of metabolic changes, including loss body fat; however, there is still no consensus in the academic community about whether both strength and aerobic exercise equally reduces adiposity. Therefore, this study aimed to evaluate the effects of strength training and aerobic exercise regimes on adiposity, proteins regulating mitochondrial activity, and respiratory complexes in BAT of old rats. The rats were divided in two control groups: young control (YC; N = 5), and old control (OC; N = 5), and two exercise groups: strength training (OST; N = 5), and aerobic treadmill training (OAT; N = 5). Rats were subjected to an 8-week exercise regime, and their body composition parameters were evaluated (total body weight, adiposity index, and BAT weight). In addition, mitochondrial biogenesis proteins (PGC-1α, SIRT1, and pAMPK) and respiratory chain activity (complexes I, II/III, III, and IV) were evaluated. Results showed that OST and OAT exercise protocols significantly increased the mitochondrial regulatory molecules and respiratory chain activity, while body fat percentage and adiposity index significantly decreased. Taken together, both OST and OAT exercise increased BAT weight, activity of respiratory complexes, and regulatory proteins in BAT and equally reduced body adiposity.

Multi-regulatory network of ROS: the interconnection of ROS, PGC-1 alpha, and AMPK-SIRT1 during exercise.

Transcriptional factors are easily susceptible to any stimuli, including exercise. Exercise can significantly influence PGC-1 α and AMPK-SIRT1 pathway, as it is involved in the regulation of energy metabolism and mitochondrial biogenesis. Exercise is a major energy deprivation process by which many of transcription factors get tuned positively. However, how transcription factors help to boost the antioxidant defense system at cellular level is elusive. It is well known that physical exercise can induce reactive oxygen species, but how these reactive oxygen species can help to regulate multiple transcription factors during exercise is an important area to be discussed yet. This review mainly focuses on interconnecting role of PGC-1 α and AMPK-SIRT1 pathway during exercise and how these proteins are getting tuned by reactive oxygen species in exercise condition.

Gold nanoparticles prevent cognitive deficits, oxidative stress and inflammation in a rat model of sporadic dementia of Alzheimer's type.

Alzheimer's disease (AD) is the most common form of neurodegenerative dementia in the aged brain. Even though its etiology is unknown, factors such as neuroinflammation, mitochondrial dysfunction, formation of reactive oxygen species (ROS), and impaired insulin signaling may play a role. We used a sporadic AD model in rats generated by intracerebroventricular-streptozotocin (i.c.v.-STZ) injection to test the therapeutic effect of gold nanoparticles (GNPs). We tested the null hypothesis that there would be no difference between the STZ+GNPs group and the STZ group in the analyzed markers. We observed that STZ-induced impairment in mitochondrial ATP production, neuroinflammation, and oxidative stress were all prevented by GNP treatment. Moreover, while STZ induced deficits in both spatial and recognition memory, GNPs prevented this effect. These results suggest that GNPs may be considered as a potential treatment for dementias.

Extracellular superoxide dismutase is necessary to maintain renal blood flow during sepsis development.

BACKGROUND: Extracellular superoxide dismutase (ECSOD) protects nitric oxide (NO) bioavailability by decreasing superoxide levels and preventing peroxynitrite generation, which is important in maintaining renal blood flow and in preventing acute kidney injury. However, the profile of ECSOD expression after sepsis is not fully understood. Therefore, we intended to evaluate the content and gene expression of superoxide dismutase (SOD) isoforms in the renal artery and their relation to renal blood flow. METHODS: Sepsis was induced in Wistar rats by caecal ligation and perforation. Several times after sepsis induction, renal blood flow (12, 24 and 48 h); the renal arterial content of SOD isoforms, nitrotyrosine, endothelial and inducible nitric oxide synthase (e-NOS and i-NOS), and phosphorylated vasodilator-stimulated phosphoprotein (pVASP); and SOD activity (3, 6 and 12 h) were measured. The influence of a SOD inhibitor was also evaluated. RESULTS: An increase in ECSOD content was associated with decreased 3-nitrotyrosine levels. These events were associated with an increase in pVASP content and maintenance of renal blood flow. Moreover, previous treatment with a SOD inhibitor increased nitrotyrosine content and reduced renal blood flow. CONCLUSIONS: ECSOD appears to have a major role in decreasing peroxynitrite formation in the renal artery during the early stages of sepsis development, and its application can be important in renal blood flow control and maintenance during septic insult.

Prior Exercise Training Prevent Hyperglycemia in STZ Mice by Increasing Hepatic Glycogen and Mitochondrial Function on Skeletal Muscle.

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. We investigated the effect of a prior 30 days voluntary exercise protocol on STZ-diabetic CF1 mice. Glycemia, and the liver and skeletal muscle glycogen, mitochondrial function, and redox status were analyzed up to 5 days after STZ injection. Animals were engaged in the following groups: Sedentary vehicle (Sed Veh), Sedentary STZ (Sed STZ), Exercise Vehicle (Ex Veh), and Exercise STZ (Ex STZ). Exercise prevented fasting hyperglycemia in the Ex STZ group. In the liver, there was decreased on glycogen level in Sed STZ group but not in EX STZ group. STZ groups showed decreased mitochondrial oxygen consumption compared to vehicle groups, whereas mitochondrial H2 O2 production was not different between groups. Addition of ADP to the medium did not decrease H2 O2 production in Sed STZ mice. Exercise increased GSH level. Sed STZ group increased nitrite levels compared to other groups. In quadriceps muscle, glycogen level was similar between groups. The Sed STZ group displayed decreased O2 consumption, and exercise prevented this reduction. The H2 O2 production was higher in Ex STZ when compared to other groups. Also, GSH level decreased whereas nitrite levels increased in the Sed STZ compared to other groups. The PGC1 α levels increased in Sed STZ, Ex Veh, and Ex STZ groups. In summary, prior exercise training prevents hyperglycemia in STZ-mice diabetic associated with increased liver glycogen storage, and oxygen consumption by the mitochondria of skeletal muscle implying in increased oxidative/biogenesis capacity, and improved redox status of both tissues. J. Cell. Biochem. 118: 678-685, 2017. © 2016 Wiley Periodicals, Inc.

Topiramate effects lipolysis in 3T3-L1 adipocytes.

Studies have shown that topiramate (TPM)-induced weight loss can be dependent on the central nervous system (CNS). However, the direct action of TPM on adipose tissue has not been tested previously. Thus, the present study aimed to examine whether TPM modulates lipolysis in 3T3-L1. The 3T3-L1 cells were incubated in 50 µM TPM for 30 min. The ß-adrenergic stimulator, isoproterenol, was used as a positive control. The release of lactate dehydrogenase, non-esterified fatty acid, glycerol and incorporation of 14C-palmitate to lipid were analyzed. The phosphorylation of protein kinase A (PKA), hormone-sensitive lipase (HSL), adipocyte triglyceride lipase (ATGL) and perilipin A, as well as the protein levels of comparative genetic identification 58 (CGI-58) were assessed. The levels of glycerol and non-esterified fatty acid increased markedly when the cells were treated with TPM. The TPM effects were similar to the isoproterenol positive control. Additionally, TPM reduced lipogenesis. These results were observed without any change in cell viability. Finally, the phosphorylation of PKA, HSL, ATGL and perilipin A, as well as the protein levels of CGI-58 were increased compared to the control cells. These results were similar to those observed in the cells treated with isoproterenol. The present results show that TPM increased the phosphorylation of pivotal lipolytic enzymes, which induced lipolysis in 3T3-L1 adipocytes, suggesting that this drug may act directly in the adipose tissue independent from its effect on the CNS.

Hypothalamic energy metabolism is impaired by doxorubicin independently of inflammation in non-tumour-bearing rats.

We sought to explore the effects of doxorubicin on inflammatory profiles and energy metabolism in the hypothalamus of rats. To investigate these effects, we formed two groups: a control (C) group and a Doxorubicin (DOXO) group. Sixteen rats were randomly assigned to either the control (C) or DOXO groups. The hypothalamus was collected. The levels of interleukin (IL)-1ß, IL-6, IL-10, TNF-α and energy metabolism (malate dehydrogenase, complex I and III activities) were analysed in the hypothalamus. The DOXO group exhibited a decreased body weight (p < 0.01). Hypothalamic malate dehydrogenase activity was reduced when compared with control (p < 0.05). In addition, pro-inflammatory cytokine levels were unchanged. Therefore, our results demonstrate that doxorubicin leads to an impairment of \hypothalamic energy metabolism, but do not affect the inflammatory pathway. SIGNIFICANCE PARAGRAPH: The hypothalamus is a central organ that regulates a great number of functions, such as food intake, temperature and energy expenditure, among others. Doxorubicin can lead to deep anorexia and metabolic chaos; thus, we observed the effect of this chemotherapeutic drug on the inflammation and metabolism in rats after the administration of doxorubicin in order to understand the central effect in the hypothalamus. Drug treatment by doxorubicin is used as a cancer therapy; however the use of this drug may cause harmful alterations to the metabolism. Thus, further investigations are needed on the impact of drug therapy over the long term.

Inflammatory cytokines content in Achilles tendinopathy after phonophoresis treatment combined with gold nanoparticles and diclophenac diethylammonium in rats.

Tendinitis is a painful condition that occurs in tendons in response to repetitive use or direct trauma. The therapeutic approaches commonly employed to modulate inflammation have not achieved complete success in chronic cases of tendinitis. In this scenario, considering the anti-inflammatory properties of pulsed therapeutic ultrasound and gold nanoparticles (GNPs), this study assesses the possible therapeutic effects of phonophoresis in association with diclophenac diethylammonium and GNPs by measuring the inflammatory parameters interleukin 1ß and tumor necrosis factor alpha in acute tendinous injury. Wistar rats were randomly divided into three groups and were treated with phonophoresis and diclophenac diethylammonium, GNP gel, and a combination thereof. A significant decrease in interleukin 1ß and tumor necrosis factor alpha occurred in tendons treated with phonophoresis+diclophenac+GNPs. The content of both cytokines were similar after combined treatment with phonophoresis+diclophenac+GNPs. Apart from the anti-inflammatory effect, GNPs transported and enhanced drug action when used with phonophoresis.

Role of training and detraining on inflammatory and metabolic profile in infarcted rats: influences of cardiovascular autonomic nervous system.

The aim of this study was to evaluate the effects of exercise training (ET, 50-70% of VO2 max, 5 days/week) and detraining (DT) on inflammatory and metabolic profile after myocardial infarction (MI) in rats. Male Wistar rats were divided into control (C, n = 8), sedentary infarcted (SI, n = 9), trained infarcted (TI, n = 10; 3 months of ET), and detrained infarcted (DI, n = 11; 2 months of ET + 1 month of DT). After ET and DT protocols, ventricular function and inflammation, cardiovascular autonomic modulation (spectral analysis), and adipose tissue inflammation and lipolytic pathway were evaluated. ET after MI improved cardiac and vascular autonomic modulation, and these benefits were correlated with reduced inflammatory cytokines on the heart and adipose tissue. These positive changes were sustained even after 1 month of detraining. No expressive changes were observed in oxidative stress and lipolytic pathway in experimental groups. In conclusion, our results strongly suggest that the autonomic improvement promoted by ET, and maintained even after the detraining period, was associated with reduced inflammatory profile in the left ventricle and adipose tissue of rats subjected to MI. These data encourage enhancing cardiovascular autonomic function as a therapeutic strategy for the treatment of inflammatory process triggered by MI.

Exercise training decreases mitogen-activated protein kinase phosphatase-3 expression and suppresses hepatic gluconeogenesis in obese mice.

Insulin plays an important role in the control of hepatic glucose production. Insulin resistant states are commonly associated with excessive hepatic glucose production, which contributes to both fasting hyperglycaemia and exaggerated postprandial hyperglycaemia. In this regard, increased activity of phosphatases may contribute to the dysregulation of gluconeogenesis. Mitogen-activated protein kinase phosphatase-3 (MKP-3) is a key protein involved in the control of gluconeogenesis. MKP-3-mediated dephosphorylation activates FoxO1 (a member of the forkhead family of transcription factors) and subsequently promotes its nuclear translocation and binding to the promoters of gluconeogenic genes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). In this study, we investigated the effects of exercise training on the expression of MKP-3 and its interaction with FoxO1 in the livers of obese animals. We found that exercised obese mice had a lower expression of MKP-3 and FoxO1/MKP-3 association in the liver. Further, the exercise training decreased FoxO1 phosphorylation and protein levels of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and gluconeogenic enzymes (PEPCK and G6Pase). These molecular results were accompanied by physiological changes, including increased insulin sensitivity and reduced hyperglycaemia, which were not caused by reductions in total body mass. Similar results were also observed with oligonucleotide antisense (ASO) treatment. However, our results showed that only exercise training could reduce an obesity-induced increase in HNF-4α protein levels while ASO treatment alone had no effect. These findings could explain, at least in part, why additive effects of exercise training treatment and ASO treatment were not observed. Finally, the suppressive effects of exercise training on MKP-3 protein levels appear to be related, at least in part, to the reduced phosphorylation of Extracellular signal-regulated kinases (ERK) in the livers of obese mice.

Overtraining is associated with DNA damage in blood and skeletal muscle cells of Swiss mice.

BACKGROUND: The alkaline version of the single-cell gel (comet) assay is a useful method for quantifying DNA damage. Although some studies on chronic and acute effects of exercise on DNA damage measured by the comet assay have been performed, it is unknown if an aerobic training protocol with intensity, volume, and load clearly defined will improve performance without leading to peripheral blood cell DNA damage. In addition, the effects of overtraining on DNA damage are unknown. Therefore, this study aimed to examine the effects of aerobic training and overtraining on DNA damage in peripheral blood and skeletal muscle cells in Swiss mice. To examine possible changes in these parameters with oxidative stress, we measured reduced glutathione (GSH) levels in total blood, and GSH levels and lipid peroxidation in muscle samples. RESULTS: Performance evaluations (i.e., incremental load and exhaustive tests) showed significant intra and inter-group differences. The overtrained (OTR) group showed a significant increase in the percentage of DNA in the tail compared with the control (C) and trained (TR) groups. GSH levels were significantly lower in the OTR group than in the C and TR groups. The OTR group had significantly higher lipid peroxidation levels compared with the C and TR groups. CONCLUSIONS: Aerobic and anaerobic performance parameters can be improved in training at maximal lactate steady state during 8 weeks without leading to DNA damage in peripheral blood and skeletal muscle cells or to oxidative stress in skeletal muscle cells. However, overtraining induced by downhill running training sessions is associated with DNA damage in peripheral blood and skeletal muscle cells, and with oxidative stress in skeletal muscle cells and total blood.

Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats.

It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRß/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRß/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging.

Effects of gold nanoparticles on endotoxin-induced uveitis in rats.

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.

Sleep duration in elderly obese patients correlated negatively with intake fatty.

STUDY OBJECTIVES: The purpose of the present study was to evaluate the relationship between sleep duration and dietary habits in elderly obese patients treated at an institute of cardiology. METHODS: The fifty-eight volunteers were elderly patients with obesity (classified as obese according to BMI) of both genders, between 60 and 80 years of age. All participants were subjected to assessments of food intake, anthropometry, level of physical activity, and duration of sleep. RESULTS: The men had significantly greater weight, height, and waist circumference than women. Sleep durations were correlated with dietary nutrient compositions only in men. We found a negative association between short sleep and protein intake (r = -0.43; p = 0.02), short sleep and monounsaturated fatty acids intake (r = -0.40; p = 0.03), and short sleep and cholesterol dietary intake (r = -0.50; p = 0.01). CONCLUSIONS: We conclude that mainly in men, volunteers that had short sleep duration showed a preference for high energy-density as fatty food, at least in part, may explain the relationship between short sleep duration and the development of metabolic abnormalities.

Therapeutic action of physical exercise on markers of oxidative stress induced by chronic kidney disease.

AIMS: To investigate the effects physical training exerts on markers of oxidative stress in rats with chronic kidney disease (CKD). MAIN METHODS: Twenty-four male Wistar rats were divided into four groups (n=6): sham, CKD, exercise-sham and exercise-CKD. Surgical reduction of the renal mass was performed (5/6 nephrectomized) and exercise was conducted on a treadmill (50 min/day up to 1 km/h for, 5 days/week for eight weeks). Forty-eight hours after the last exercise session, blood (1 mL) was collected from the abdominal aorta and animals were decapitated. The left kidney was surgically removed and stored at -70 °C for subsequent analysis. KEY FINDINGS: An increase was observed in creatinine and urea levels, superoxide production, antioxidant enzymes, and oxidative damage in the CKD group, as compared to sham animals (p<0.05). Physical training made superoxide production and oxidative damage decrease in the CKD group (p<0.05), increasing SOD and GPX activity, though it did not increase the antioxidant effects of CAT, and renal parameters. SIGNIFICANCE: Even without altering renal function in animals induced to CKD model, the results show that physical training is an important component in the treatment of CKD, because it exerted a positive influence on oxidative stress parameters, especially on the reduction in superoxide production and oxidative damage, as well as an improvement in the antioxidant defense system, like SOD and GPX.