Thiago Duarte

Association between ischemia-modified albumin, lipids and inflammation biomarkers in patients with hypercholesterolemia.

OBJECTIVES The aim of this study was to evaluate the association between ischemia-modified albumin (IMA), lipids and inflammation biomarkers in patients with hypercholesterolemia, and the possible involvement of IMA in atheromatous plaque development and oxidative stress. DESIGN AND METHODS Glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, oxidized LDL (ox-LDL), ox-LDL autoantibodies, high-sensitivity C reactive protein (hs-CRP), and IMA were measured in 37 subjects with hypercholesterolemia and 37 controls. RESULTS Total cholesterol, LDL cholesterol, triglycerides, ox-LDL, ox-LDL autoantibodies, hs-CRP, and IMA were higher in the hypercholesterolemia group, and HDL cholesterol levels were lower in this group. We observed significant correlations between IMA and total cholesterol, LDL cholesterol, ox-LDL antibodies, and hs-CRP levels. Significant correlations were also observed between hs-CRP and total cholesterol, HDL cholesterol, LDL cholesterol, ox-LDL, ox-LDL autoantibodies, and triglycerides. CONCLUSIONS Hypercholesterolemia is associated with an increase in inflammatory and oxidative stress biomarkers, and it also reduces the capacity of albumin to bind cobalt owing to ischemia, resulting in an increased IMA. IMA formation appears to be associated with oxidative stress and atheromatous plaque development.

Oxidative stress in hypercholesterolemia and its association with Ala16Val superoxide dismutase gene polymorphism

OBJECTIVES To investigate the role of the oxidative stress and the antioxidant system as well as the influence of the manganese superoxide dismutase (Ala16Val) polymorphism on hypercholesterolemia. DESIGN AND METHODS Levels of glucose, lipid, high-sensitivity C reactive protein (hs-CRP), thiobarbituric acid reactive substances (TBARS), carbonyl protein, thiols, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and vitamin C, vitamin E, as well as the presence of the manganese superoxide dismutase (Ala16Val) polymorphism were determined in 40 subjects with hypercholesterolemia and 40 controls. RESULTS Lipid profile, hs-CRP, glucose, TBARS, carbonyl protein, CAT, and vitamin E were significantly higher in subjects with hypercholesterolemia. In contrast, GSH and SOD were lower. TBARS, carbonyl protein, thiols, CAT, and vitamin E were significantly higher in hypercholesterolemic subjects with VV genotype for MnSOD, while GSH, SOD, and vitamin C were lower in these subjects. CONCLUSIONS We suggest an association between the genotypes of MnSOD, hypercholesterolemia, and oxidative stress biomarkers.

Assessment of Inflammatory and Oxidative Biomarkers in Obesity and Their Associations with Body Mass Index

The aim of this study was to evaluate the inflammatory and oxidative biomarkers’ levels in obese subjects and their associations with body mass index (BMI), in order to investigate the role of these biomarkers in obesity. Fasting glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apolipoprotein A, apolipoprotein B, albumin, urinary albumin, creatinine, glomerular filtration rate, interleukin-6 (IL-6), nitrate/nitrite (NOx), and ischemia-modified albumin (IMA) were measured in 93 subjects divided according to different BMI. IL-6, urinary albumin, and IMA levels were significantly higher in obese subjects. However, the levels of NOx were significantly lower in this population. Significant correlations between BMI and IL-6 (r = 0.326, P = 0.002), NOx (r = −0.249, P = 0.021), urinary albumin (r = 0.270, P = 0.008), and IMA (r = 0.286, P = 0.005) were reported. We have shown an increase of IL-6, urinary albumin, and IMA combined with lower levels of NOx in obese patients and an association between of these biomarkers with BMI, suggesting a possible interplay of oxidative stress, inflammation, and endothelial dysfunction state in obesity.

Association between DNA strand breakage and oxidative, inflammatory and endothelial biomarkers in type 2 diabetes

Evidence has been presented recently that type 2 diabetes patients have an increased level of DNA damage. This DNA damage could be associated with oxidative, inflammatory, and endothelial biomarkers and could represent a possible indication of injury in the endothelium and induction of inflammation in type 2 diabetes. To confirm this possible association, DNA strand breakage was evaluated by use of the comet assay and its association with oxidative, inflammatory, and endothelial biomarkers in type 2 diabetes patients. A case-control study (30 healthy controls and 32 subjects with type 2 diabetes) was performed to evaluate the association between DNA damage and NOx (nitrate/nitrite), interleukin-6 (IL-6), urinary albumin, fasting glucose, and glycated hemoglobin (HbA(1c)) levels. Type 2 diabetes patients presented higher DNA damage than control subjects, higher levels of IL-6 and urinary albumin, and lower NOx. Significant correlations between DNA damage and NOx (r=-0.303, p=0.016), IL-6 (r=0.845, p<0.001), urinary albumin (r=0.496, p<0.001), fasting glucose (r=0.449, p<0.001), and HbA(1c) (r=0.575, p<0.001) were reported. Our findings showed an increase of DNA damage in type 2 diabetes especially in those patients with poor glycemic control and associations among NOx, IL-6 and urinary albumin levels with DNA damage.

Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as indicators of tubular damage in normoalbuminuric patients with type 2 diabetes.

OBJECTIVES Renal dysfunction has been reported in normoalbuminuric patients, demonstrating the necessity to improve the diagnostic and prognostic tools for diabetic kidney disease (DKD) investigation. Therefore, the aim of this study was to investigate whether the urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are increased in type 2 diabetes mellitus (DM) patients with normal or mildly increased albuminuria. DESIGN AND METHODS In this study, 117 type 2 DM patients classified into three groups according to urinary albumin/creatinine ratio (uACR): uACR<10mg/g creatinine, uACR 10-30mg/g creatinine and uACR>30mg/g creatinine were enrolled. Urinary concentrations of KIM-1 (uKIM-1) and NGAL (uNGAL) were measured. RESULTS uKIM-1 levels increased progressively from uACR<10mg/g creatinine (69.0±20.8pg/ml) to uACR 10-30mg/g creatinine (106.1±41.2pg/ml) and to uACR>30mg/g creatinine (166.0±31.9pg/ml) (P<0.001). In addition, uNGAL levels increased progressively from uACR<10mg/g creatinine (29.5±8.8ng/ml) to uACR 10-30mg/g creatinine (51.7±10.9ng/ml) and to uACR>30mg/g creatinine (71.0±9.6ng/ml) (P<0.001) patients. Similarly, both uKIM-1 and uNGAL adjusted by urinary creatinine were increased in patients with uACR 10-30mg/g creatinine. Significant and positive correlations were observed between uACR, uKIM-1 and uNGAL. CONCLUSIONS uKIM-1 and uNGAL were increased in type 2 DM patients with normal or mildly increased albuminuria, which indicates that tubular and glomerular injuries may be occurring even at the earliest stage of DKD.

Response of oxidative stress and inflammatory biomarkers to a 12-week aerobic exercise training in women with metabolic syndrome

BackgroundEvidences have been highlighted the relationship among metabolic syndrome, chronic low-grade inflammation, oxidative stress and several diseases. In this sense, the aim of this study was to investigate the effects of aerobic exercise training on oxidative stress and inflammatory parameters on women with metabolic syndrome (MS).MethodsTwenty-three untrained women (51.86 ± 6.58 years old, BMI 30.8 ± 4.3 kg/m2) completed a 12-week treadmill exercise training, without modifications on dietary pattern. Advanced oxidation protein products (AOPP), thiobarbituric acid-reactive substances (TBARS), total thiol content (T-SH) and nitrite and nitrate (NOx) levels were assessed in plasma while the levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ) were evaluated in the serum. The RNA expression (mRNA) of IL-1β, IL-10, TNF-α, IFN-γ, insulin receptor substrate 2 (IRS-2) and matrix metalloproteinase-9 (MMP-9) were performed inperipheral blood mononuclear cells (PBMC) of a subset with eight women with MS using real real-time polymerase chain reaction (qPCR).ResultsThe intervention resulted in decreased serum levels of IL-1β, IL-6, TNF-α, IFN-γ, AOPP and TBARS, besides increased levels of IL-10 and T-SH (P < 0.001). NOx concentrations were unchanged, similarly to mRNA expressions quantified in PBMC.ConclusionsTwelve weeks of AT improved systemic oxidative stress and inflammatory biomarkers in women with MS, although PBMC mRNA expression for inflammatory pathways appeared to be unchanged. This may indicate that AT induced beneficial effects not only in physical fitness but also on health promotion through decreased oxidative damage and proinflammatory status.

Novel markers of inflammatory response and hepatic dysfunction in canine leishmaniasis.

Dogs are the main host of Leishmania infantum, and the clinical presentation may range from asymptomatic to systemic manifestations. The immune mechanisms in infected, but clinically healthy dogs, prevails Th1 response mediated by cytokines. In this sense, adenosine deaminase (ADA) and butyrylcholinesterase (BChE) are considered as key enzymes in several physiological processes, including the modulation of inflammatory process. Considering the variable immune response against Leishmania and the known participation of ADA and BChE, the aim of this study was to assess the relation between these two enzymes with the inflammatory response as well as hepatic function in dogs naturally infected with L. infantum. For this purpose, the activity of ADA and BChE was assessed in sera of 24 dogs naturally infected with L. infantum, plus 17 healthy dogs. The naturally infected dogs had clinical signs compatible with leishmaniasis and sera activities of ADA (P<0.01) and BChE (P<0.05) decreased, when compared to the healthy group. The reduction of ADA activity probably represented an effect on inflammatory response, especially due to the decreased hydrolysis of extracellular adenosine, might in order to protect against tissue damage and, also, setting a down-regulation on pro-inflammatory cytokines. BChE enzyme had no effect on modulating the immune response in leishmaniasis, but it decreased, a fact may related to deficiency of synthesis in the liver. Therefore, ADA and BChE activities reduced probably in order to protect against extra tissue damage and due failure in synthesis, respectively.

A novel isoquinoline compound abolishes chronic unpredictable mild stress-induced depressive-like behavior in mice

Chronic unpredictable mild stress (CUMS) elicits aspects of cognitive and behavioral alterations that can be used to model comparable aspects of depression in humans. The aim of the present study was to investigate the antidepressant-like potential of 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI), a novel isoquinoline compound, in CUMS, a model that meets face, construct and predictive criteria for validity. Swiss mice were subjected to different stress paradigms daily for a period of 35 days to induce the depressive-like behavior. The animals received concomitant FDPI (0.1 and 1mg/kg, intragastric) or paroxetine (8mg/kg, intraperitoneal) and CUMS. The behavioral tests (splash test, tail suspension test, modified forced swimming test and locomotor activity) were performed. The levels of cytokines, corticosterone and adrenocorticotropic (ACTH) hormones were determined in the mouse prefrontal cortex and serum. The synaptosomal [(3)H] serotonin (5-HT) uptake, nuclear factor (NF)-κB, tyrosine kinase receptor (TrkB) and pro-brain-derived neurotrophic factor (BDNF) levels were determined in the mouse prefrontal cortex. CUMS induced a depressive-like behavior in mice, which was demonstrated in the modified forced swimming, tail suspension and splash tests. FDPI at both doses prevented depressive-like behavior induced by CUMS, without altering the locomotor activity of mice. FDPI at the highest dose prevented the increase in the levels of NF-kB, pro-inflammatory cytokines, corticosterone and ACTH and modulated [(3)H]5-HT uptake and the proBDNF/TrkB signaling pathway altered by CUMS. The present findings demonstrated that FDPI elicited an antidepressant-like effect in a model of stress-induced depression.

Oxidative DNA damage is associated with inflammatory response, insulin resistance and microvascular complications in type 2 diabetes

Urinary markers of nucleic acid oxidation may be useful biomarkers in diabetes. It has been demonstrated that T2DM patients have an increased level of oxidative DNA damage; however, it is unclear whether increased DNA damage may be related to a greater degree of inflammation and insulin resistance. Thus, the aim of this present study was to investigate the relation of the impact of oxidative DNA damage, assessed by urinary 8-OHdG, on the levels of inflammatory cytokines, as well as insulin resistance. In addition, we also investigated the diagnostic ability of urinary 8-OHdG in the identification of microvascular complications in T2DM.A case-control study, enrolling 22 healthy controls and 54 subjects with T2DM, was performed to evaluate the relation between oxidative DNA damage and interleukin-6 (IL-6), IL-1,tumor necrosis factor-alpha (TNF-α), IL-10, and Homeostasis Model Assessment (HOMA-IR) index. T2DM patients presented higher urinary 8-OHdG, IL-6, IL-1, TNF-α levels and HOMA-IR, and lower IL-10 levels than control subjects. Moreover, urinary 8-OHdG levels were significantly higher in the group T2DM with microvascular complications when compared to the without complications. The areas under the curve for urinary 8-OHdG and urinary albumin were, respectively, 0.836 (P<0.001) and 0.786 (P=0.002). Thus, urinary 8-OHdG has a slightly higher ability to discriminate microvascular complications in T2DM compared with urinary albumin. It was also demonstrated that T2DM patients with higher median of urinary 8-OHdG had significantly elevated levels of IL-6, TNF-α and HOMA-IR, and decreased IL-10 levels. Our findings showed that T2DM patients with higher urinary 8-OHdG levels showed a greater inflammatory degree and higher insulin resistance. It is possible to speculate that T2DM patients present a cascade of events as increasing metabolic abnormalities such as insulin resistance and inflammatory activation, as well as increased ROS generation factors that may contribute directly to greater oxidative DNA damage.

Assessment of Oxidative, Inflammatory, and Fibrinolytic Biomarkers and DNA Strand Breakage in Hypercholesterolemia

The aim of this study was to assess the levels of oxidative, inflammatory, and fibrinolytic biomarkers as well as DNA strand breakage in hypercholesterolemic subjects. Fasting glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, uric acid, total protein, albumin, apolipoprotein (Apo) A, Apo B, advanced oxidation protein products (AOPP), increased ischemia-modified albumin (IMA), ―SH, NOx, IL-6, and D-dimer levels were assessed, and DNA strand breakage was evaluated using comet assay in 38 patients with hypercholesterolemia and 20 healthy controls. Total cholesterol, triglycerides, LDL cholesterol, Apo A, Apo B, AOPP, IMA, IL-6, and D-dimer concentrations were significantly higher in subjects with hypercholesterolemia. However, NOx and plasma ―SH group concentrations were lower in hypercholesterolemic subjects, while no significant differences were observed with respect to DNA strand breakage between the two groups. Hypercholesterolemia is related to oxidative stress and inflammation. Accordingly, AOPP concentration was higher in subjects with hypercholesterolemia, and we speculate that AOPP can reflect the enhancement of protein oxidation and inflammation.