3-nitrotyrosine and Metabolic-Syndrome

This study assessed plasmatic antioxidant capabilities and xanthine oxidase (XOX) activity in metabolic syndrome patients after 5 years intervention with Mediterranean diet (MeDiet) supplemented with extra-virgin olive oil or with nuts or with low-fat diet (the PREDIMED [PREvención con Dieta MEDiterránea] study).. Seventy-five participants were randomly selected. Daily energy and nutrient intake were assessed with a validated 137-item food frequency questionnaire, and adherence to the MeDiet was assessed using a 14-item questionnaire. Catalase, superoxide dismutase (SOD), myeloperoxidase, XOX activities and protein levels, and protein carbonyl derivatives, nitrotyrosine, nitrite and nitrate levels were determined in overnight fasting venous blood samples. The plasma activity and protein levels of SOD and catalase were significantly higher and XOX activity was lower in MeDiet supplemented with extra-virgin olive oil and MeDiet supplemented with nuts than in the control group. Participants in both MeDiet groups showed higher plasma nitrate levels than in the control group. Adherence to the MeDiet showed a positive correlation with SOD and catalase plasma antioxidant activities.. A MeDiet enriched with either virgin olive oil or nuts enhances the plasma antioxidant capabilities and decreases XOX activity in patients with the metabolic syndrome but we did not observe changes in myeloperoxidase or markers of oxidative damage.

Topics: Aged; Aged, 80 and over; Biomarkers; Catalase; Cholesterol; Diet, Fat-Restricted; Diet, Mediterranean; Female; Follow-Up Studies; Humans; Male; Metabolic Syndrome; Middle Aged; Nutrition Assessment; Nuts; Olive Oil; Patient Compliance; Peroxidase; Superoxide Dismutase; Surveys and Questionnaires; Tyrosine; Xanthine Oxidase

In this pathbreaking study, we evaluated nitrosative stress in morbidly obese patients with and without metabolic syndrome. 62 women with class 3 obesity (BMI > 40 kg/m

Topics: Adult; Area Under Curve; Female; Glutathione; Glutathione Disulfide; Humans; Hypertension; Metabolic Syndrome; Middle Aged; Nitric Oxide; Nitrosative Stress; Obesity, Morbid; Oxidation-Reduction; Peroxidase; Peroxynitrous Acid; ROC Curve; Sulfhydryl Compounds; Tyrosine

Exposure to hand-transmitted vibration in the work-place can result in the loss of sensation and pain in workers. These effects may be exacerbated by pre-existing conditions such as diabetes or the presence of primary Raynaud's phenomena. The goal of these studies was to use an established model of vibration-induced injury in Zucker rats. Lean Zucker rats have a normal metabolic profile, while obese Zucker rats display symptoms of metabolic disorder or Type II diabetes. This study examined the effects of vibration in obese and lean rats. Zucker rats were exposed to 4h of vibration for 10 consecutive days at a frequency of 125 Hz and acceleration of 49 m/s(2) for 10 consecutive days. Sensory function was checked using transcutaneous electrical stimulation on days 1, 5 and 9 of the exposure. Once the study was complete the ventral tail nerves, dorsal root ganglia and spinal cord were dissected, and levels of various transcripts involved in sensorineural dysfunction were measured. Sensorineural dysfunction was assessed using transcutaneous electrical stimulation. Obese Zucker rats displayed very few changes in sensorineural function. However they did display significant changes in transcript levels for factors involved in synapse formation, peripheral nerve remodeling, and inflammation. The changes in transcript levels suggested that obese Zucker rats had some level of sensory nerve injury prior to exposure, and that exposure to vibration activated pathways involved in injury and re-innervation.

Topics: Animals; Biophysics; Chemokine CCL2; Disease Models, Animal; Ganglia, Spinal; Gene Expression Regulation; Hyperalgesia; Interleukin-1beta; Male; Metabolic Syndrome; Neuralgia; Nitric Oxide Synthase Type I; Rats; Rats, Zucker; Receptors, Adrenergic, alpha-2; RNA, Messenger; Time Factors; Transcutaneous Electric Nerve Stimulation; Tyrosine; Vibration

Metabolic syndrome (MetS) is a combination of clinical disorders that together increase the risk for cardiovascular disease and diabetes. SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP.ZF) rats with MetS show impaired nitric oxide-mediated relaxation in coronary and mesenteric arteries, and angiotensin II receptor type 1 blockers protect against dysfunction and oxidative-nitrosative stress independently of metabolic effects. We hypothesize that superoxide contributes to functional deterioration in SHRSP.ZF rats. To test our hypothesis, we studied effects of treatment with tempol, a membrane-permeable radical scavenger, on impaired vasodilation in SHRSP.ZF rats. Tempol did not alter body weight, high blood pressure, or metabolic abnormalities, but prevented impairment of acetylcholine-induced and nitroprusside-induced vasodilation in the coronary and mesenteric arteries. Furthermore, tempol reduced the levels of serum thiobarbituric acid reactive substance (TBARS) and 3-nitrotyrosine content in mesenteric arteries. Systemic administration of tempol elevated the expression of soluble guanylate cyclase (sGC) above basal levels in mesenteric arteries of SHRSP.ZF rats. However, acute treatment with tempol or ebselen, a peroxynitrite scavenger, did not ameliorate impaired relaxation of isolated mesenteric arteries. No nitration of tyrosine residues in sGC was observed; however, sGC mRNA expression levels in the arteries of SHRSP.ZF rats were lower than those in the arteries of Wistar-Kyoto rats. Levels of Thr(496)- and Ser(1177)-phosphorylated endothelial nitric oxide synthase (eNOS) were lower in arteries of SHRSP.ZF rats, and acetylcholine decreased Thr(496)-phosphorylated eNOS levels. These results indicated that prolonged superoxide production, leading to oxidative-nitrosative stress, was associated with impaired vasodilation in SHRSP.ZF rats with MetS. Down-regulated sGC expression may be linked to dysfunction, while reduced NO bioavailability/eNOS activity and modified sGC activity due to superoxide production were excluded as pivotal mechanisms.

Topics: Animals; Azoles; Coronary Vessels; Cyclic N-Oxides; Disease Models, Animal; Down-Regulation; Free Radical Scavengers; Guanylate Cyclase; Heart; Isoindoles; Male; Metabolic Syndrome; Nitric Oxide; Nitric Oxide Synthase Type III; Nitrogen; Organoselenium Compounds; Oxidative Stress; Phosphorylation; Rats; Receptor, Angiotensin, Type 1; RNA, Messenger; Spin Labels; Superoxides; Tyrosine; Vasodilation

The aim of this study was to evaluate the effect of DTS-phytocompound on oxidant-antioxidant balance and protein damage in the kidneys of rats administered high doses of fructose. Adult male Wistar rats were divided into four groups. Group A received a control diet, whereas groups B and C were fed a high-fructose diet (60 g/100 g), the latter with additional DTS (50 mg/kg per day) for 60 days. Lipo- and nitro-peroxidation together with α-smooth muscle actin (α-SMA) expression in the glomerular and interstitial tissue of the kidneys were measured after 60 days. Fructose-fed rats showed significantly higher lipoperoxidation, 2,4-dinitrophenol and 3-nitrotyrosine protein adducts, and upregulation of α-SMA in the kidney. DTS significantly decreased such redox unbalance in renal tissue, while partially downregulating α-SMA (p<0.01). These data suggest the potential clinical benefit of DTS in protecting the kidneys from metabolic syndrome-associated changes; gender-related analysis is under way.

Topics: 2,4-Dinitrophenol; Animals; Antioxidants; Fructose; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Metabolic Syndrome; Oxidation-Reduction; Oxidative Stress; Phytotherapy; Rats; Rats, Wistar; Tyrosine

Metabolic syndrome (MetS) confers a greater risk for both cardiovascular disease (CVD) and diabetes. Oxidative stress (OS) could contribute to this excess risk. However, there are few data examining both cellular and circulating biomarkers of OS in MetS uncomplicated by diabetes and CVD.. The aim of the study was to evaluate both cellular and circulating biomarkers of OS in MetS uncomplicated by diabetes or CVD.. At an academic medical center, we compared MetS (n=43) vs. control subjects (n=33). Fasting blood was collected for monocyte isolation and assay of OS biomarkers.. Monocyte nicotinamide adenine dinucleotide phosphate oxidase activity (p22 phox and p47), superoxide anion release, oxidized-low-density lipoprotein (Ox-LDL), nitrotyrosine, and nuclear factor erythroid 2-related factor were measured.. There was significantly increased release of superoxide from the monocytes (basal and after activation) of MetS compared with controls adjusted for body mass index. Body mass index-adjusted plasma levels of Ox-LDL and nitrotyrosine were significantly increased in MetS. There was a linear trend between biomarkers of oxidative stress and increasing number of features of MetS. Also, there was a significant increase in nicotinamide adenine dinucleotide phosphate oxidase membrane expression of p22 phox and p47 phox in MetS. The major cellular antioxidant defense, nuclear factor erythroid 2-related factor was significantly decreased. There were significant correlations between homeostasis model assessment insulin resistance index and both Ox-LDL and nitrotyrosine and superoxide and Ox-LDL.. Collectively, nascent MetS is associated with increased OS as evidenced by both circulating and cellular biomarkers, and this could contribute to the risk for both diabetes and CVD.

Topics: Adult; Biomarkers; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged; Monocytes; NADPH Oxidases; NF-E2 Transcription Factor; Oxidative Stress; Prevalence; Risk Factors; Superoxides; Tyrosine

Asymmetric dimethylarginine (ADMA) is an endogenous modulator of endothelial function and oxidative stress, and increased levels of this molecule have been reported in some metabolic disorders and cardiovascular diseases. The aim of this work was to analyze the time course of dimethylarginine compounds and oxidative stress levels and the relationship between these and cardiovascular function in fructose-hypertensive rats.. 90 male Sprague-Dawley rats were randomized into 2 groups, fed for 3 months with standard (C) chow supplemented or not with fructose (F, 60%). After sacrifice at different weeks (W), the aorta and plasma were harvested to assess the vascular and biochemical parameters. Our work showed that the plasma levels of ADMA in the fructose-fed rats increased after 2 weeks of the diet (1.6 ± 0.3 μM vs. 1.2 ± 0.3 μM, p < 0.05) with no changes in plasma levels of either SDMA or L-arginine and after an increase in glycemia. Levels of vascular oxidative stress, estimated in aortic segments using an oxidative fluorescence technique, were higher in the F group (W2: 1.14 ± 0.2% vs. 0.33 ± 0.02%, p < 0.01). An increase in expression levels of nitrotyrosine (3-fold) and iNOS (2-fold) were noted in the fructose-fed rats. After 1 month, this was associated with a significant increase in NAD(P)H oxidase activity. Concerning vascular function, a 15% decrease in maximal endothelium-dependent relaxation was found in the aorta of the F group. Our work showed that the presence of exogenous L-MMA, an inhibitor of NO synthase, was associated with a significant reduction in endothelium-dependent relaxation in isolated aorta rings of the C group; this effect was not observed in the vessels of fructose-fed rats.. Our findings suggest that the elevated levels of ADMA observed could in part be secondary to the early development of oxidative stress associated with the development of hypertension.

Topics: Animals; Aorta; Arginine; Blood Glucose; Blood Pressure; Body Weight; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors; Fructose; Heart Rate; Hypertension; Male; Metabolic Syndrome; NADPH Oxidases; Nitric Oxide Synthase Type II; Oxidative Stress; Rats; Rats, Sprague-Dawley; Time Factors; Tyrosine; Vasodilation; Vasodilator Agents

Metabolic syndrome is known to facilitate the development of cardiovascular disease. We have demonstrated that mesenteric arteries of SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP-fatty) rats with metabolic syndrome display an impaired vasorelaxation response mediated by nitric oxide. We examined whether the condition could be alleviated by treatment with telmisartan, an angiotensin II type 1 (AT1) receptor antagonist with PPAR-γ-activating properties and compared the results with those from pioglitazone, a PPAR-γ agonist. Telmisartan (5 mg·kg(-1)·day(-1)) or pioglitazone (2.5 mg·kg(-1)·day(-1)) was orally administered to male SHRSP-fatty rats for 8 weeks. Serum triglyceride and cholesterol levels were determined, and the oral glucose tolerance test was performed to evaluate insulin resistance. Vasodilations in response to acetylcholine and nitroprusside were determined by wire myographs under isometric tension conditions, protein expressions of soluble guanylyl cyclase in mesenteric arteries by Western blotting, and the contents of 3-nitrotyrosine in aortas by high-performance liquid chromatography with electrochemical detection. Telmisartan exerted antihypertensive effects, while pioglitazone ameliorated metabolic abnormalities in SHRSP-fatty rats. Telmisartan increased acetylcholine- and nitroprusside-induced relaxation and soluble guanylyl cyclase protein expression in mesenteric arteries and reduced 3-nitrotyrosine content in aortas. Pioglitazone displayed no such alleviating effects on vascular functions. These findings indicate that telmisartan protects against vasodilation disturbance through anti-oxidative and -nitrative stress independently of metabolic effects in SHRSP-fatty rats with metabolic syndrome.

Topics: Acetylcholine; Animals; Antihypertensive Agents; Benzimidazoles; Benzoates; Blood; Blood Glucose; Blood Pressure; Cholesterol; Crosses, Genetic; Guanylate Cyclase; Hypoglycemic Agents; Insulin; Male; Mesenteric Arteries; Metabolic Syndrome; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type III; Nitroprusside; Phenylephrine; Pioglitazone; Rats; Rats, Inbred SHR; Rats, Zucker; Receptors, Cytoplasmic and Nuclear; Soluble Guanylyl Cyclase; Telmisartan; Thiazolidinediones; Triglycerides; Tyrosine; Vasoconstriction; Vasodilation

We have previously reported that peroxynitrite is involved in dysfunction of nitric oxide (NO)-mediated vasorelaxation in SHR/NDmcr-cp rats (SHR-cp), which display typical symptoms of metabolic syndrome. This study investigated whether peroxynitrite is actually generated in the vascular wall with angiotensin II-induced NADPH-oxidase activation, thus contributing to the dysfunction. In isolated mesenteric arteries of male 18-week-old SHR-cp, relaxations in response to acetylcholine and sodium nitroprusside were impaired compared with that in Wistar-Kyoto rats. This impaired relaxation was not restored by treatment with apocynin, an NADPH-oxidase inhibitor. Protein expression of endothelial NO synthase increased while that of soluble guanylyl cyclase (sGC) decreased in the artery. We observed increased production of superoxide anions and peroxynitrite from the artery and their inhibition by apocynin, and also increased contents of nitrotyrosine, a biomarker of peroxynitrite, in mesenteric arteries and angiotensin II in aortas. Long-term (8 weeks) administration of telmisartan, an angiotensin II type 1-receptor antagonist, prevented the impaired vasorelaxation, decreased sGC expression and increased nitrotyrosine content in mesenteric arteries. These findings suggest that in the vascular wall of SHR-cp, peroxynitrite is continually produced by the reaction of NO with NADPH oxidase-derived superoxide via angiotensin II and gradually denatures sGC protein, leading to vasorelaxation dysfunction.

Topics: Acetylcholine; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzimidazoles; Benzoates; Blood Vessels; Blotting, Western; Enzyme Activation; Immunoenzyme Techniques; Luminescence; Male; Metabolic Syndrome; NADPH Oxidases; Nitric Oxide Synthase Type III; Nitroprusside; Peroxynitrous Acid; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Telmisartan; Tyrosine; Vasoconstrictor Agents; Vasodilation

Metabolic syndrome (MetS) is a group of cardiovascular risk factors, including visceral obesity, glucose intolerance, hypertension, and dyslipidemia. Increased oxidative and nitrative stress and inflammation and decreased endothelial function occur in an animal model of metabolic syndrome, SHR/NDmcr-cp (SHR/cp) rats. The present study investigated the effects of coenzyme Q10 (CoQ10), one of the important antioxidants, on the abnormal oxidative condition and characteristic components of metabolic syndrome in SHR/cp rats by maintaining them on a diet supplemented with 0.07% - 0.7% CoQ10 for 26 weeks. We determined serum levels of oxidatively modified low-density lipoprotein (Ox-LDL) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as oxidative stress markers, 3-nitrotyrosine as a nitrative stress marker, 3-chlorotyrosine as a marker of myeloperoxidase (MPO)-catalyzed oxidation and high-sensitivity C-reactive protein (hsCRP) as an inflammatory marker. The administration of CoQ10 significantly attenuated the increase of oxidative and nitrative stress markers and inflammatory markers in a dose-dependent manner. CoQ10 prevented the elevated serum insulin levels, although it did not affect the elevated glucose level and dyslipidemia. CoQ10 also reduced elevated blood pressure, but did not affect body weight gain. In addition, CoQ10 improved endothelial dysfunction in the mesenteric arteries. These findings suggest that the antioxidant properties of CoQ10 can be effective for ameliorating cardiovascular risk in MetS.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Body Weight; Deoxyguanosine; Disease Models, Animal; Inflammation; Insulin; Lipids; Lipoproteins, LDL; Metabolic Syndrome; Oxidative Stress; Peroxidase; Rats; Rats, Inbred SHR; Tyrosine; Ubiquinone

Type II diabetes mellitus (DM) and metabolic syndrome are associated with accelerated restenosis following vascular interventions due to neointimal hyperplasia. The efficacy of nitric oxide (NO)-based therapies is unknown in these environments. Therefore, the aim of this study is to examine the efficacy of NO in preventing neointimal hyperplasia in animal models of type II DM and metabolic syndrome and examine possible mechanisms for differences in outcomes. Aortic vascular smooth muscle cells (VSMC) were harvested from rodent models of type II DM (Zucker diabetic fatty), metabolic syndrome (obese Zucker), and their genetic control (lean Zucker). Interestingly, NO inhibited proliferation and induced G0/G1 cell cycle arrest to the greatest extent in VSMC from rodent models of metabolic syndrome and type II DM compared with controls. This heightened efficacy was associated with increased expression of cyclin-dependent kinase inhibitor p21, but not p27. Using the rat carotid artery injury model to assess the efficacy of NO in vivo, we found that the NO donor PROLI/NO inhibited neointimal hyperplasia to the greatest extent in type II DM rodents, followed by metabolic syndrome, then controls. Increased neointimal hyperplasia correlated with increased reactive oxygen species (ROS) production, as demonstrated by dihydroethidium staining, and NO inhibited this increase most in metabolic syndrome and DM. In conclusion, NO was surprisingly a more effective inhibitor of neointimal hyperplasia following arterial injury in type II DM and metabolic syndrome vs. control. This heightened efficacy may be secondary to greater inhibition of VSMC proliferation through cell cycle arrest and regulation of ROS expression, in addition to other possible unidentified mechanisms that deserve further exploration.

Topics: Animals; Aorta, Abdominal; Apoptosis; Carotid Artery Injuries; Cell Cycle; Cell Proliferation; Cells, Cultured; Diabetes Mellitus, Type 2; Disease Models, Animal; DNA Replication; Dose-Response Relationship, Drug; Hyperplasia; Male; Metabolic Syndrome; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Nitric Oxide; Nitric Oxide Donors; Proline; Rats; Rats, Zucker; Reactive Oxygen Species; S-Nitroso-N-Acetylpenicillamine; Triazenes; Tyrosine

Obese Zucker rats, animal model for the metabolic syndrome, develop a diabetes-like neuropathy that is independent of hyperglycemia. The purpose of this study was to determine whether drugs used to treat cardiovascular dysfunction in metabolic syndrome also protect nerve function.. Obese Zucker rats at 20 weeks of age were treated for 12 weeks with enalapril or rosuvastatin. Lean rats were used as controls. Vasodilation in epineurial arterioles was measured by videomicroscopy. Endoneurial blood flow (EBF) was measured by hydrogen clearance and nerve conduction velocity was measured following electrical stimulation of motor or sensory nerves.. Enalapril treatment decreased serum angiotensin-converting enzyme (ACE) activity and both drugs reduced serum cholesterol levels. In obese Zucker rats at 32 weeks of age superoxide levels were elevated in the aortas and epineurial arterioles, which were reduced by treatment with either drug. Nitrotyrosine levels were increased in epineurial arterioles and reduced with enalapril treatment. EBF was decreased and corrected by treatment with either drug. Motor nerve conduction velocity was decreased and significantly improved with enalapril treatment. Obese Zucker rats were hypoalgesic in response to a thermal stimulus and this was significantly improved with either treatment. Treatment with either enalapril or rosuvastatin significantly reversed the decrease in acetylcholine-mediated vascular relaxation of epineurial arterioles in obese Zucker rats.. Even though obese Zucker rats have normal glycemia vascular and neural dysfunctions develop with age and can be improved by treatment with either enalapril or rosuvastatin.

Topics: Acetylcholine; Angiotensin-Converting Enzyme Inhibitors; Animals; Arterioles; Cardiovascular System; Disease Models, Animal; Enalapril; Fluorobenzenes; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Metabolic Syndrome; Motor Neurons; Neural Conduction; Neurons, Afferent; Nociceptors; Obesity; Peripheral Nerves; Pyrimidines; Rats; Rats, Zucker; Rosuvastatin Calcium; Sciatic Nerve; Sulfonamides; Superoxides; Tyrosine; Vasodilator Agents

Endothelial dysfunction is a key event in the development of renovascular complications in the metabolic syndrome. The aim of this study was to elucidate the pathogenetic mechanisms involved in renovascular injuries in the Zucker obese rat, a model of the metabolic syndrome, and to examine the therapeutic effects of pioglitazone, a thiazolidinedione. Obese rats fed high-protein diet (OHP) for 12 weeks exhibited nephropathy and endothelial dysfunction, which were improved by pioglitazone. Accumulation of nitrotyrosine, a tracer of nitrative stress, was increased in aorta of the OHP group. The mRNA expressions of NADPH oxidase components and inducible nitric oxide synthase in the aorta were enhanced in the OHP group. Pioglitazone reduced nitrotyrosine in the aorta of the OHP group, inhibiting the augmented expression levels of both. These results suggest that nitrative stress could cause endothelial dysfunction in the rat model of metabolic syndrome with nephropathy, and that pioglitazone ameliorates these injuries, presumably by reducing nitrative stress.

Topics: Animals; Endothelium, Vascular; Kidney Diseases; Kidney Glomerulus; Male; Metabolic Syndrome; NADPH Oxidases; Obesity; Pioglitazone; Polymerase Chain Reaction; Rats; Rats, Zucker; RNA, Messenger; Thiazolidinediones; Tyrosine; Vasodilation

Although nonalcoholic fatty liver disease (NAFLD) is associated with the metabolic syndrome, the mechanisms responsible for the development of NAFLD at different stages of the development of insulin resistance are unknown. Diet, adipokines, and nitrosative stress have been linked to both NAFLD and insulin resistance.. We aimed to identify the factors that are specifically associated with NAFLD at different stages in the development of insulin resistance and the metabolic syndrome.. Circulating concentrations of adipokines (ie, tumor necrosis factor-alpha, adiponectin, resistin, leptin, and interleukin-6), markers of nitrosative stress (nitrotyrosine), dietary habits, and MTP -493G/T polymorphism were cross-sectionally related to the presence and severity of insulin resistance (homeostasis model assessment index for insulin resistance: >or=2), the metabolic syndrome, and fatty liver in 64 nonobese nondiabetic patients with NAFLD (33 insulin-sensitive and 31 insulin-resistant subjects) and 74 control subjects without liver disease who were matched for sex, BMI, homeostasis model assessment index for insulin resistance status, and the various features of the metabolic syndrome.. Persons with NAFLD had greater systemic nitrosative stress and a lower intake of vitamins A and E than did control subjects, but the 2 groups did not differ significantly in any other features. Nitrotyrosine and adiponectin concentrations and vitamin A intakes independently predicted alanine aminotransferase concentrations in NAFLD patients and liver histology in a subgroup of 29 subjects with biopsy-proven nonalcoholic steatohepatitis.. Oxidative stress is operating in NAFLD and nonalcoholic steatohepatitis, even in the absence of insulin resistance, the metabolic syndrome, and hypoadiponectinemia, which aggravate liver histology at more severe stages of metabolic disease. The possible pathogenetic role of reduced vitamin A intake in NAFLD warrants further investigation.

Topics: Adipokines; Analysis of Variance; Biomarkers; Carrier Proteins; Case-Control Studies; Fatty Liver; Feeding Behavior; Female; Humans; Insulin Resistance; Liver; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Polymorphism, Genetic; Risk Factors; Severity of Illness Index; Tyrosine; Vitamin A

Corosolic acid (CRA), a constituent of banaba leaves, has been reported to have anti-inflammatory and hypoglycemic activities. The aim of this study was to determine the effects of CRA on metabolic risk factors including obesity, hypertension, hyperinsulinemia, hyperglycemia, and hyperlipidemia together with oxidative stress and inflammation, all of which are characteristic of the SHR/NDmcr-cp (cp/cp) (SHR-cp) rat, an animal model of metabolic syndrome. Six-week-old male SHR-cp rats were fed a high fat diet containing 0.072% CRA for 14 weeks. Treatment with CRA lowered blood pressure, which was elevated in control animals, by 10% after 8 weeks, and serum free fatty acids by 21% after 2 weeks. CRA treatment resulted in decreases in the levels of the oxidative stress markers thiobarbituric acid-reactive substances and 8-hydroxydeoxyguanosine by 27% and 59%, respectively, after 2 weeks. CRA treatment also reduced the levels of myeloperoxidase markers, 3-nitrotyrosine and 3-chlorotyrosine by 38% and 39%, respectively, after 10 weeks, and tended to decrease the levels of high sensitivity C-reactive protein, a marker of inflammation, after 6 weeks. However, CRA had no effect on weight gain or hyperglycemia. These results demonstrate that CRA can ameliorate hypertension, abnormal lipid metabolism, and oxidative stress as well as the inflammatory state in SHR-cp rats. This implies that CRA can be beneficial for preventing atherosclerosis-related diseases that are an increasing health care problem worldwide.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Blood Pressure; Body Weight; Cholesterol; Deoxyguanosine; Disease Models, Animal; Fatty Acids, Nonesterified; Hypertension; Inflammation; Insulin; Male; Metabolic Syndrome; Molecular Structure; Musa; Oxidative Stress; Phytotherapy; Plant Extracts; Rats; Rats, Inbred SHR; Thiobarbituric Acid Reactive Substances; Triglycerides; Triterpenes; Tyrosine

The metabolic syndrome represents a cluster of several risk factors for atherosclerosis that increases the risk of future cardiovascular events. In this study, we evaluated whether oxidative stress is increased in subjects with the metabolic syndrome. We studied 100 subjects (50 men and 50 women) with the metabolic syndrome, as defined by the Adult Treatment Panel III, and 50 (25 men and 25 women) matched subjects without the syndrome. Insulin sensitivity was assessed with the homeostasis model assessment (HOMA) methods; endothelium-dependent flow-mediated vasodilation (FMD) was evaluated in the right brachial artery with a high-resolution ultrasound machine; oxidative stress was assessed by measuring the circulating levels of nitrotyrosine (NT), considered a good marker for the formation of endogenous peroxynitrite. Compared with control subjects, patients with the metabolic syndrome had greater waist circumference, higher HOMA and systolic pressure values, higher triglyceride and lower HDL-cholesterol levels. NT levels were higher (0.44+/-0.12 micromol/l, mean+/-SD) while FMD was lower [7.3 (4.4/9.6), median and interquartile range] in subjects with the metabolic syndrome as compared with control subjects [0.27+/-0.08 and 11.8 (8.6/14.9), respectively, p<0.001]. There was an increase in NT levels and HOMA score as the number of components of the metabolic syndrome increased. NT levels were associated with waist circumference (r=0.38, p=0.01), triglycerides (r=0.32, p<0.02), systolic blood pressure (r=0.21, p<0.05) and fasting glucose (r=0.24, p<0.05). The oxidative stress that accompanies the metabolic syndrome is associated with both insulin resistance and endothelial dysfunction, providing a connection which is highly deleterious for vascular functions.

Topics: Adult; Blood Glucose; Blood Pressure; Brachial Artery; Case-Control Studies; Female; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Regional Blood Flow; Tyrosine; Vasodilation