Association of Free Radical Product and Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis.

PURPOSE: Polycystic ovary syndrome (PCOS) is an endocrine disorder that primarily affects women of reproductive age. It is recognized as the leading cause of infertility due to anovulation. This research aims to evaluate the diagnostic potential of oxidative stress biomarkers, including advanced oxidation protein products (AOPP), malondialdehyde (MDA), uric acid (UA), and nitric oxide (NO), in identifying PCOS. METHODS: A literature search was conducted in the EMBASE, PubMed, Cochrane Library, and Scopus databases. The standardized mean difference (SMD) and 95% confidence interval (CI) were employed to assess the correlation between free radical product and PCOS. Moreover, the presence of heterogeneity among the studies was assessed utilizing the I2 statistic and Cochran Q test. The methodological rigor of the incorporated studies was assessed through the application of the Newcastle-Ottawa Scale. Furthermore, the presence of publication bias was determined via Begg and Egger tests. RESULTS: This meta-analysis reviewed 38 observational studies, including 17,845 women. The results revealed a significant association between PCOS in women and alterations in free radical levels. The study revealed that the PCOS group had significantly higher levels of AOPP (SMD = 3.193; 95% CI, 2.86 to 3.25), UA (SMD = 0.68; 95% CI, 0.24 to 1.13), and MDA (SMD = 1.16; 95% CI, 0.77 to 1.56) compared to the healthy control group. Furthermore, the analysis found a significantly lower level of NO (SMD = (- 0.59); 95% CI, - 1.15 to - 0.03) in the PCOS patient. CONCLUSION: Screening of specific biomarkers associated with free radical products could provide valuable benefits in the prognosis and diagnosis of PCOS.

Effect of Normobaric Hypoxia on Alterations in Redox Homeostasis, Nitrosative Stress, Inflammation, and Lysosomal Function following Acute Physical Exercise.

Hypoxia is a recognized inducer of oxidative stress during prolonged physical activity. Nevertheless, previous studies have not systematically examined the effects of normoxia and hypoxia during acute physical exercise. The study is aimed at evaluating the relationship between enzymatic and nonenzymatic antioxidant barrier, total antioxidant/oxidant status, oxidative and nitrosative damage, inflammation, and lysosomal function in different acute exercise protocols under normoxia and hypoxia. Fifteen competitive athletes were recruited for the study. They were subjected to two types of acute cycling exercise with different intensities and durations: graded exercise until exhaustion (GE) and simulated 30 km individual time trial (TT). Both exercise protocols were performed under normoxic and hypoxic (FiO2 = 16.5%) conditions. The number of subjects was determined based on our previous experiment, assuming the test power = 0.8 and α = 0.05. We demonstrated enhanced enzymatic antioxidant systems during hypoxic exercise (GE: ↑ catalase (CAT), ↑ superoxide dismutase; TT: ↑ CAT) with a concomitant decrease in plasma reduced glutathione. In athletes exercising in hypoxia, redox status was shifted in favor of oxidation reactions (GE: ↑ total oxidant status, ↓ redox ratio), leading to increased oxidation/nitration of proteins (GE: ↑ advanced oxidation protein products (AOPP), ↑ ischemia-modified albumin, ↑ 3-nitrotyrosine, ↑ S-nitrosothiols; TT: ↑ AOPP) and lipids (GE: ↑ malondialdehyde). Concentrations of nitric oxide and its metabolites (peroxynitrite) were significantly higher in the plasma of hypoxic exercisers with an associated increase in inflammatory mediators (GE: ↑ myeloperoxidase, ↑ tumor necrosis factor-alpha) and lysosomal exoglycosidase activity (GE: ↑ N-acetyl-ß-hexosaminidase, ↑ ß-glucuronidase). Our study indicates that even a single intensive exercise session disrupts the antioxidant barrier and leads to increased oxidative and nitrosative damage at the systemic level. High-intensity exercise until exhaustion (GE) alters redox homeostasis more than the less intense exercise (TT, near the anaerobic threshold) of longer duration (20.2 ± 1.9 min vs. 61.1 ± 5.4 min-normoxia; 18.0 ± 1.9 min vs. 63.7 ± 3.0 min-hypoxia), while hypoxia significantly exacerbates oxidative stress, inflammation, and lysosomal dysfunction in athletic subjects.

Level of advanced oxidation protein products is associated with subclinical atherosclerosis.

BACKGROUND: Oxidative stress is an important factor in the pathomechanism of atherosclerosis. Advanced oxidation protein products (AOPPs) are considered markers of oxidative stress. Thickening of the carotid intima-media layers indicates subclinical atherosclerosis and can be detected by carotid ultrasound. OBJECTIVE: Our aim was to examine the association between carotid intima-media thickness (CIMT) and the level of AOPPs. METHODS: Carotid duplex scans and measurements of AOPPs were performed on 476 participants of a cardiovascular population study. The presence of conventional cardiovascular risk factors was investigated with a questionnaire, physical examination, and laboratory tests. RESULTS: There was a positive correlation between maximum CIMT and the level of AOPPs only in the male population (r = 0.219, p = 0.033). Multivariate analysis has revealed that the association between AOPPs and mean or maximum CIMT was independent of cardiovascular risk factors (OR = 1.458, p = 0.004, and OR = 2.038, p < 0.001). CONCLUSIONS: Among males, the elevated level of AOPPs as a marker of oxidative stress may signal the existence of early atherosclerotic alterations.

Association of Low Molecular Weight Plasma Aminothiols with the Severity of Coronavirus Disease 2019.

OBJECTIVE: Aminothiols (glutathione (GSH), cysteinylglycine (CG)) may play an important role in the pathogenesis of coronavirus disease 2019 (COVID-19), but the possible association of these indicators with the severity of COVID-19 has not yet been investigated. METHODS: The total content (t) and reduced forms (r) of aminothiols were determined in patients with COVID-19 (n = 59) on admission. Lung injury was characterized by computed tomography (CT) findings in accordance with the CT0-4 classification. RESULTS: Low tGSH level was associated with the risk of severe COVID-19 (tGSH ≤ 1.5 µM, mild vs. moderate/severe: risk ratio (RR) = 3.09, p = 0.007) and degree of lung damage (tGSH ≤ 1.8 µM, CT < 2 vs. CT ≥ 2: RR = 2.14, p = 0.0094). The rGSH level showed a negative association with D-dimer levels (ρ = -0.599, p = 0.014). Low rCG level was also associated with the risk of lung damage (rCG ≤ 1.3 µM, CT < 2 vs. CT ≥ 2: RR = 2.28, p = 0.001). Levels of rCG (ρ = -0.339, p = 0.012) and especially tCG (ρ = -0.551, p = 0.004) were negatively associated with platelet count. In addition, a significant relationship was found between the advanced oxidation protein product level and tGSH in patients with moderate or severe but not in patients with mild COVID-19. CONCLUSION: Thus, tGSH and rCG can be seen as potential markers for the risk of severe COVID-19. GSH appears to be an important factor to oxidative damage prevention as infection progresses. This suggests the potential clinical efficacy of correcting glutathione metabolism as an adjunct therapy for COVID-19.

Advanced Oxidative Protein Products Role in Multiple Sclerosis: a Systematic Review and Meta-analysis.

Multiple sclerosis (MS) is an autoimmune-mediated disease that damages the central nervous system. MS pathophysiological features are not entirely understood, but the increase of reactive oxygen species (ROS) possibly causes myelin and oligodendrocyte degeneration. ROS-increased production generates new compounds through oxidative modifications, including advanced oxidative protein products (AOPPs). The AOPPs are oxidative stress biomarkers and inflammatory mediators commonly formed by hypochlorous acid oxidative action on albumin. Considering that AOPPs accumulation produces ROS and induces neuronal apoptosis, these may represent a new target for drug development to MS treatment and a possible biomarker to monitor the severity of the disease. Thus, this review aims to investigate if there is an alteration in the AOPPs levels in MS and its possible involvement in patient disability. The second objective is to analyze whether drugs or compounds used in MS treatment could modify the AOPPs levels. The protocol was registered in PROSPERO (CRD42020203268). The databases' search yielded 327 articles. We excluded 259 duplicated articles and evaluated 68 articles by the title and abstract. We full-text analyzed 17 articles and included 13 articles. The AOPPs levels were increased in not-treated MS patients. Furthermore, the increase in disability status was associated with AOPPs accumulation in not-treated MS patients. Additionally, the AOPPs levels were reduced in MS patients after treatment. Therefore, AOPPs seem to play a role in MS pathophysiology and may become a new target for drug development and help MS diagnosis or treatment follow-up.

Circulating extracellular DNA is in association with continuous metabolic syndrome score in healthy adolescents.

Obesity is associated with chronic low-grade inflammation that eventually leads to metabolic complications. Extracellular DNA (ecDNA) is a damage-associated molecular pattern. Extracellular mitochondrial DNA can activate innate immunity. We hypothesized that ecDNA, especially of mitochondrial origin, could be associated with components of the metabolic syndrome in young healthy probands. In a cross-sectional study, healthy adolescents (n = 1,249) provided blood samples. Anthropometric data, blood pressure, and blood counts were assessed. In addition, biochemical analysis of sera or plasma was conducted, including the quantification of advanced oxidation protein products (AOPPs) as a marker of oxidative stress induced by neutrophil or monocyte activation. Plasma ecDNA was isolated and measured by fluorometry. Nuclear and mitochondrial DNA were quantified by real-time PCR. Males had higher total plasma ecDNA [15 (11-21) vs. 11 (8-17) ng/mL; median (interquartile range)], nuclear [1,760 (956-3,273) vs. 1,153 (600-2,292) genome equivalents (GE)/mL], and mitochondrial [37,181 (14,836-90,896) vs. 30,089 (12,587-72,286) GE/mL] DNA. ecDNA correlated positively with the continuous metabolic syndrome score (r = 0.158 for males and r = 0.134 for females). Stronger correlations were found between ecDNA of mitochondrial origin and AOPP (r = 0.202 and 0.186 for males and females, respectively). Multivariate regression analysis revealed associations of nuclear DNA with leukocyte and erythrocyte counts. The results of this study of healthy adolescents show that circulating ecDNA is associated with the risk of metabolic syndrome, not with obesity per se. The association between mitochondrial ecDNA and AOPP requires further attention as it supports a potential role of mitochondria-induced sterile inflammation in the pathogenesis of the metabolic syndrome.

The evaluation of oxidative stress parameters in breast and colon cancer.

ABSTRACT: Our aim in this study was to investigate the relationship between serum ischemia modified albumin (IMA) levels with oxidative stress parameters [protein carbonyl (PCO), advanced protein oxidation products (AOPPs), malondialdehyde (MDA), total nitric oxide (NOx), prooxidant-antioxidant balance (PAB), and ferric reducing of antioxidant power (FRAP)] in breast cancer (BC) and colon cancer (CC).In total, 90 patients undergoing surgical treatment for BC (n = 45) or CC (n = 45) and 35 healthy controls were included in this cross-sectional study.The serum PCO, AOPPs, MDA, NOx, PAB, and IMA levels were all statistically significantly higher in the cancer patients than in the control group. MDA, NOx, and PAB levels were significantly lower in the BC group than in the CC group. FRAP values were statistically significantly lower in both the CC group and the BC group compared to the control. IMA showed a weak positive correlation with CA-19.9 (r = 0.423 P = .007) but a moderate positive correlation with tumor size in the CC group. IMA showed a positive correlation with metastasis, grade, and HER2 and a negative correlation with ER and PR in the BC group.Oxidative stress is a key player in the development of solid malignancies. Cancer development is a multistage process, and oxidative stress caused by the production of ROS/RNS in the breast and colon may predispose individuals to BC and CC. Patients with BC and CC had an impaired oxidative/antioxidant condition that favored oxidative stress. The ROC analysis indicated that IMA sensitivity above 80% could be used as a secondary biomarker in diagnosis.

Advanced Oxidation Protein Product (AOPP) Levels in Second- and Third-Degree Thermal Burns.

Burn is a systemic injury affecting the entire organism according to its etiology and severity. The aim of this study was to investigate plasma AOPP levels before and after treatment of second- and third-degree thermal burn patients and determine the changes in this parameter, and also, to find out the relationship between AOPP level and hospitalization period and total body surface area (TBSA). The study material consisted of pediatric patients with the complaint of second- and third-degree thermal burns aged between 1 and 18 years, with a burn area exceeding 10%. Blood samples were taken twice before and after treatment. AOPP level in blood plasma was measured in ELISA. It was observed that in the second-degree thermal burn group, AOPP level was 25.85 ± 2.82 ng/ml before the treatment decreased to 22.16 ± 3.62 ng/ml after treatment, whereas in the third-degree thermal burn group before the treatment AOPP was 25.96 ± 3.49 ng/ml, and after the treatment dropped to 21.70 ± 3.79 ng/ml, decreases were significantly important (P < .05). There was no statistically significant difference between the two groups in terms of AOPP levels (P > .05). Correlation analyses in the second- and third-degree thermal burn group did not show any correlation between AOPP levels and burn area and length of hospitalization period. As a result, AOPP level has been studied, for the first time, in burn cases. In both groups, the level of AOPP increased due to oxidative stress before treatment and decreased after treatment.

Relationship between serum hepcidin levels and cardiovascular disease in patients with maintenance hemodialysis.

BACKGROUND: To investigate the serum level of hepcidin and its relationship with cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients. METHODS: Blood was obtained from 75 MHD patients before undergoing hemodialysis and 20 healthy controls. Serum hepcidin, advanced oxidation protein products (AOPP) and interleukin (IL)-6 were measured by enzyme-linked immunosorbant assay (ELISA). Spearman correlation, and binary logistic regression linear regression analyses were used to assess the relationship between serum hepcidin and other parameters. RESULTS: The serum level of hepcidin, AOPP and IL-6 was significantly up-regulated in MHD patients compared with the control (P < 0.05). Furthermore, serum hepcidin levels in patients with CVD were higher than those in patients without CVD (P < 0.05). In all MHD patients, serum hepcidin level was correlated positively with erythropoietin (EPO) dose per week (ρ = 0.251, P = 0.030), EPO resistance index (ρ = 0.268, P = 0.020), ferritin (ρ = 0.814, P < 0.001), transferin saturation (TSAT, ρ = 0.263, P = 0.023), AOPP (ρ = 0.280, P = 0.049), high sensitive C reactive protein (ρ = 0.151, P = 0.006), IL-6 (ρ = 0.340, P = 0.003) and left ventricular mass index (LVMI, ρ = 0.290, P = 0.033). Moreover, it was negatively correlated with serum pre-albumin (ρ = -0.266, P = 0.021), total iron-binding capacity (TIBC, ρ = -0.458, P < 0.001), unsaturated iron-binding capacity (UIBC, ρ = -0.473, P < 0.001) and transferrin (ρ = -0.487, P < 0.001). Linear regression analysis showed that ferritin (ß = 0.708, P < 0.001), TIBC (ß = -0.246, P = 0.032) and IL-6 (ß = 0.209, P = 0.041) were independently associated with hepcidin. Results of binary logistic regression analysis suggested that higher serum hepcidin level (>249.2 ng/mL) was positively and independently related to CVD (OR = 1.32, 95% CI [1.20-9.56], P = 0.043). CONCLUSIONS: Serum hepcidin level is associated with CVD in MHD patients, indicating that hepcidin may be a novel biomarker and therapeutic target for CVD.

Predictive value of oxidative stress biomarkers in drug­free patients with schizophrenia and schizo-affective disorder.

Several studies have suggested that oxidative stress may represent one of the primary etiological mechanisms of schizophrenia (SZ) and schizoaffective disorder (SAD) which can be targeted by therapeutic intervention. The present study was conducted over a period of 24 months, between June 2016 and June 2018. All enrolled subjects were Tunisian, forty five drug­free male patients with SZ (mean age: 37.6 years), twenty one drug­free male patients with SAD (mean age: 28.8 years) and hundred and one age and gender matched controls (mean age: 34.2 years) were enrolled in the study. Plasma reduced glutathione (GSH) and Total thiols levels were significantly decreased in patients compared to controls (respectively p<0.001; p=0.050). In addition, malondialdehyde (MDA), advanced oxidation protein products (AOPP) and protein carbonyls (PC) concentrations and glutathione peroxidase (GSH-Px) activity were significantly increased in patients compared to controls (p<0.001; p<0.001; p<0.001 and p=0.003 respectively). The binary logistic regression analysis revealed that MDA, AOPP, PC and GSH-Px could be considered as independent risk factors for SZ and SAD. When using ROC analysis, a remarkable increase in the area under the curve (AUC) with higher sensitivity (Se) and specificity (Sp) for MDA, AOPP, PC and GSH-Px combined markers was observed. The present study indicated that the identification of the predictive value of this four-selected biomarkers related to oxidative stress in drug free patients should lead to a better identification of the etiological mechanism of SZ or SAD.

Advanced glycation end-products and advanced oxidation protein products levels are correlates of duration of type 2 diabetes.

AIMS: Diabetes is associated with the excess formation of advanced glycation end-products (AGEs) and advanced oxidation protein products (AOPP), and low levels of ferric reducing ability of plasma (FRAP). However, the trend of oxidative and antioxidant markers levels according to diabetes duration is unclear. MAIN METHODS: In a case-control study, 240 patients with diabetes and 100 healthy controls were enrolled. Patients were divided into four groups according to the duration of diabetes, including newly diagnosed, 1-5, 5-10, and 10-15 years. Serum AGEs, AOPP, and FRAP levels were compared among groups. KEY FINDINGS: AGEs and AOPP were higher and FRAP was lower in patients with diabetes compared to healthy controls. Serum levels of AGEs increased progressively with increasing in diabetes duration. AGEs levels were 68.97 ± 7.28% in newly-diagnosed, 73.43 ± 12.96% in 1-5 years and 80.44 ± 13.84% in 10-15 years of diabetes duration (pairwise p-values <0.05). In linear regression analysis the correlation among AGEs, AOPP, FRAP, and diabetes duration remained significant after adjustment for age, BMI, HDL, HbA1c, waist circumference, microvascular complications, and coronary artery diseases. ROC analysis showed AGEs could predict the duration of diabetes when patients with 10-15 years duration of diabetes were compared to patients with 1-5 years duration of diabetes (AUC = 0.676, p-value = 0.003). SIGNIFICANCE: Diabetes promotes AGEs, and AOPP production, independent of glycemic control and patients age. Serum levels of AGEs increase progressively with increasing duration of diabetes. AGEs may be helpful in estimating chronicity of diabetes.

FOXO3a accumulation and activation accelerate oxidative stress-induced podocyte injury.

Podocyte injury is the primary cause of glomerular injury in diabetic nephropathy (DN). Advanced oxidation protein products (AOPPs), the triggers and markers of oxidative stress in DN, have been linked to podocyte damage. However, the underlying mechanism is not yet clear. Here, we investigated the potential role of FOXO3a, a key transcription factor in the response to stress, in mediating AOPPs-induced podocyte injury. We found that FOXO3a expression was increased in the glomeruli of kidney biopsies from patients with DN and it was positively correlated with proteinuria. The serum from patients with DN significantly increased FOXO3a and its downstream genes FasL and Bim, thereby inducing the high level of cleaved caspase3 and the loss of nephrin and podocin expressions in podocytes. Blockade of AOPPs signaling by a neutralizing antibody against the receptor of advanced glycation end products (αRAGE) abolished the effect of DN serum on podocytes, confirming the pathogenic role of AOPPs in DN serum. Downregulation of FOXO3a decreased AOPPs-induced podocyte apoptosis and restored the levels of podocyte markers nephrin and podocin, and upregulation of FOXO3a exacerbated these changes in podocytes after AOPPs treatment. Furthermore, FOXO3a specifically activated proapoptotic genes in podocytes only in the presence of AOPPs. Mechanistically, AOPPs increased the FOXO3a protein levels by inhibiting their autophagic degradation in a ROS/mTOR-dependent manner. Moreover AOPPs activated the accumulated FOXO3a by maintaining FOXO3a in the nucleus, and this process was dependent on ROS-mediated AKT signaling deactivation. These studies suggest that FOXO3a plays a critical role in mediating AOPPs-induced podocyte injury and reveal a new mechanistic linkage of oxidative stress, FOXO3a activation and podocyte injury in DN.

Endocan and advanced oxidation protein products in adult population with hypertension.

OBJECTIVE: Hypertension is closely related to oxidative stress and inflammation. Endocan is a new inflammation marker whose role is not completely elucidated in hypertension. The aim of this study was to explore the association between endocan and several oxidative stress markers [i.e., advanced oxidation protein products (AOPP), total protein sulfhydryl (SH-) groups and prooxidant-antioxidant balance (PAB)] in adult population with hypertension. PATIENTS AND METHODS: A total of 90 patients with hypertension were compared with 44 controls. Blood pressure, anthropometric and biochemical parameters were measured. Associations of clinical data with hypertension were tested with univariable and multivariable logistic ordinal regression analysis. RESULTS: Endocan and AOPP were significantly higher in hypertensive patients than in the controls (p=0.006 and p=0.046, respectively). In the multivariable logistic regression analysis, AOPP and endocan kept their independent positive associations with hypertension. As AOPP rose by 1 µmol/L and endocan rose by 1 pg/mL, the probability for hypertension presence rose by 4.2% and 32.2%, respectively and 39.9% of variation in hypertension could be explained with the Model. The area under the Receiver Operating Characteristic curve [(AUC) for AOPP=0.638 (0.550-0.719), p=0.01 and for endocan=0.679 (0.593-0.757), p<0.001] demonstrated sufficient clinical accuracy towards hypertension. On the contrary, the Model showed very good clinical accuracy [AUC= 0.825 (0.749-0.900), p<0.001]. CONCLUSIONS: Endocan and AOPP are independently correlated with hypertension in adult population and these tested markers together could be reliable parameters to discriminate patients with hypertension from normotensive ones.

The levels of advanced oxidation protein products in patients with obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is characterized by repeated episodes of complete or partial obstructions of the upper airway during sleep, frequently followed by transient hypoxemia. Advanced oxidation protein products (AOPP) are a family of oxidized protein products, and oxidative stress has a substantial role in the morbidity of OSAS. AIMS: The aim of this study was to investigate the serum levels of advanced oxidation protein products (AOPP) as a marker of oxidative stress, and their correlation with polysomnographic parameters in patients with obstructive sleep apnea syndrome (OSAS). Additionally, we investigated the effect of positive airway pressure (PAP) treatment on serum AOPP values and compared the levels before and after the treatment. METHODS: The study enrolled a total of 125 subjects including 59 patients with severe OSAS, 34 patients with moderate OSAS, 32 patients with mild OSAS, and 40 healthy controls. Mean AOPP values were compared between OSAS groups and control groups. Correlations between AOPP and polysomnographic parameters were investigated. Mean AOPP values before and after 6-month PAP therapy were compared. RESULTS: Significantly elevated AOPP levels were found in severe and moderate OSAS groups in comparison with mild OSAS and control groups. AOPP was directly correlated with apnea-hypopnea index, percentage of total time spent with oxygen saturation below 90%, oxygen desaturation index, maximum obstructive apnea duration, arousal index, and number of obstructive apneas accompanying bradycardia but inversely correlated with average SPO2 (%), minimum SPO2, and percentage of non-REM stage 3 sleep. There was no statistically significant difference between AOPP values before and after PAP therapy. CONCLUSIONS: AOPP, which is an oxidative stress marker, was found to be high in OSAS patients. Especially, high levels in moderate and severe OSAS patients may be an indicator of increased morbidity. After 6 months of PAP treatment, there was no statistically significant change in these levels.

The role of circulating soluble fms-like tyrosine kinase-1 in patients with diabetic foot ulcer: A possible mechanism of pathogenesis via a novel link between oxidative stress, inflammation and angiogenesis.

BACKGROUND: Diabetic foot ulcer (DFU) is one of the most devastating diabetic consequences leading to amputations. Oxidative stress, inflammation, vascular insufficiency and neuropathy have been linked to DFU development. Since soluble fms-like tyrosine kinase-1 (sFlt-1) is one of the anti-angiogenic factors regulating vascular endothelial growth factor (VEGF) biological activity. So, we aimed to evaluate its role in pathogenesis of DFU and its correlation with oxidative stress and inflammatory markers. METHODS: 60 type 2 diabetic patients: 30 without DFU and 30 with DFU in addition to 20 healthy controls were enrolled in the study. sFlt-1 and VEGF mRNA relative gene expressions and levels and sFlt-1/VEGF ratio were assessed. Also, Advanced oxidation protein products (AOPPs), malondialdhyde (MDA), Total thiol and, tumor necrosis factor alpha (TNF-α) levels were measured. RESULTS: sFlt-1 expression and level, AOPPs, MDA and TNF-α were significantly higher in diabetic patients as compared with the control group with highest levels in DFU patients. However, there were significant decrease in total thiol level and VEGF expression and level in diabetic patients with DFU. CONCLUSION: This study revealed that sFlt-1 is a major player in DFU pathogenesis and may be considered as a novel diagnostic biomarker for early detection of DFU.

Antioxidant and Anti-inflammatory Diagnostic Biomarkers in Multiple Sclerosis: A Machine Learning Study.

An imbalance of inflammatory/anti-inflammatory and oxidant/antioxidant molecules has been implicated in the demyelination and axonal damage in multiple sclerosis (MS). The current study aimed to evaluate the plasma levels of tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNFR)1, sTNFR2, adiponectin, hydroperoxides, advanced oxidation protein products (AOPP), nitric oxide metabolites, total plasma antioxidant capacity using the total radical-trapping antioxidant parameter (TRAP), sulfhydryl (SH) groups, as well as serum levels of zinc in 174 MS patients and 182 controls. The results show that MS is characterized by lowered levels of zinc, adiponectin, TRAP, and SH groups and increased levels of AOPP. MS was best predicted by a combination of lowered levels of zinc, adiponectin, TRAP, and SH groups yielding an area under the receiver operating characteristic (AUC/ROC) curve of 0.986 (±0.005). The combination of these four antioxidants with sTNFR2 showed an AUC/ROC of 0.997 and TRAP, adiponectin, and zinc are the most important biomarkers for MS diagnosis followed at a distance by sTNFR2. Support vector machine with tenfold validation performed on the four antioxidants showed a training accuracy of 92.9% and a validation accuracy of 90.6%. The results indicate that lowered levels of those four antioxidants are associated with MS and that these antioxidants are more important biomarkers of MS than TNF-α signaling and nitro-oxidative biomarkers. Adiponectin, TRAP, SH groups, zinc, and sTNFR2 play a role in the pathophysiology of MS, and a combination of these biomarkers is useful for predicting MS with high sensitivity, specificity, and accuracy. Drugs that increase the antioxidant capacity may offer novel therapeutic opportunities for MS.

Effects of Curcumin on the Oxidative Stress Response to a Dual Stress Challenge in Trained Men.

Firefighters and military personnel are exposed to a variety of stressors. The combination of mental and physical stress (i.e., dual stress challenges [DSCs]) results in significant oxidative stress (OS), which may contribute to cardiometabolic dysfunction. Curcumin (CUR) is an exogenous antioxidant that may attenuate such OS. Fourteen trained men participated in a randomized, cross-over design to investigate the impact of CUR on markers of OS resulting from DSC. CUR or placebo was ingested three days prior to, and the morning of, testing. The DSC involved 20 min of mental stress challenges during 35 min of cycling at 60% V̇O2 peak. Blood was sampled before, as well as immediately, 30 min, and 60 min after, exercise and analyzed for glutathione (GSH), superoxide dismutase (SOD), hydrogen peroxide (H2O2), and advanced oxidation protein products (AOPP). There was no treatment effect for any variable. However, the DSC resulted in significant reductions in SOD, H2O2, and AOPP at 30 and 60 min after exercise. Previous studies have shown that DSC results in significant OS compared to exercise alone. However, these data suggest the DSC was associated with reductions in postexercise markers of OS. Antioxidant therapy is likely not needed in trained men exposed to DSC.

Oxidative stress markers in neonatal respiratory distress syndrome: advanced oxidation protein products and 8-hydroxy-2-deoxyguanosine in relation to disease severity.

OBJECTIVE: We assessed oxidant-antioxidant status and evaluated the role of lipid peroxidation, oxidative DNA damage, and protein oxidation in the development and severity of neonatal respiratory distress syndrome (RDS). METHODS: Forty preterm neonates with RDS were compared with another 40 preterm neonates without RDS enrolled as controls. Total antioxidant capacity (TAC), malondialdehyde (MDA), advanced oxidation protein products (AOPPs), 8-hydroxy-2-deoxyguanosine (8-OHdG), and trace elements (copper and zinc) were measured in cord blood (day 0) for all neonates and repeated on day 3 for the RDS group. RESULTS: Day 0 serum levels of MDA, AOPPs, and 8-OHdG were significantly higher in neonates with RDS than controls with a further increase on day 3. Days 0 and 3 levels of TAC, copper, and zinc were significantly lower in the RDS group compared with controls. Elevated serum levels of 8-OHdG and AOPPs were associated with severe RDS, invasive mechanical ventilation, and high mortality rate. 8-OHdG and AOPPs were positively correlated with MDA, oxygenation index, duration of ventilation, and duration of hospitalization. CONCLUSIONS: Increased lipid, protein, and DNA oxidation is accompanied by alterations in the antioxidant defense status, which may play a role in the pathogenesis and severity of RDS.

Relationship of oxidative stress in the resistance to imatinib in Tunisian patients with chronic myeloid leukemia: A retrospective study.

BACKGROUND: This work aimed to evaluate oxidative stress in chronic myeloid leukemia (CML) patients treated with tunisian (IM) vs controls and in CML patients with resistance to IM vs patients without resistance to IM. METHODS: The study included 40 CML patients and 34 controls. Of 40 patients with CML, 26 patients were developed in resistance to IM. The oxidant/antioxidant markers were evaluated by spectrophotometric methods for all used samples. RESULTS: For CML patients, increased malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels were found compared to controls (P < .001; P = .01). Higher catalase (CAT) activity (P = .048) and lower superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, reduced Glutathione (GSH) and vitamin C levels were found in CML patients (P < .001). The comparison between the resistant vs no-resistant CML patients revealed higher MDA level (P = .02) and CAT and SOD activities in IM-resistant patients (P = .04, P = .03). GPx activity was reduced (P = .04). Furthermore, increased mean ratio of MDA/GSH, MDA/GPx, and SOD/(GPx + CAT) was found in IM-resistant patients as compared with no-resistant (P = .01, P = .01, P = .035). The mean ratio of GPx/GSH in the IM-resistant CML patients was lower than in IM no-resistant one (P = .039). For IM-resistant patients, we found negative correlation between MDA level and the ratio SOD/(CAT + GPx) (r = -0.46, P = .002); and positive correlation between SOD and (CAT + GPx) activities (r = 0.38, P = .06) and between GSH level and GPx activity (r = 0.53, P = .01). CONCLUSIONS: Our results have shown a highly disturbed oxidative profile in IM-resistant CML patients as compared to no-resistant. The H2 O2 has a key role in the resistance to IM treatment.

Advanced oxidation protein products in nondiabetic end stage renal disease patients on maintenance haemodialysis.

In chronic kidney disease (CKD), the impairment of the excretory function leads to elevation in the blood concentrations of urea, creatinine, and various protein metabolic products. Advanced oxidation protein products (AOPP), along with protein carbonyls, protein-bound di-tyrosines and S-thiolated proteins, are considered biomarkers of oxidative stress in end-stage renal disease (ESRD) patients on maintenance haemodialysis (HD). In this study, we evaluated the correlations between plasma levels of AOPP (measured by size exclusion/gel filtration high performance liquid chromatography) and those of protein-bound di-tyrosines, protein carbonyls, albumin and fibrinogen in 50 nondiabetic ESRD patients on maintenance HD. Considering that AOPP could represent the bridge between oxidative stress and inflammation, having been identified as proinflammatory mediators, we also evaluated the association between AOPP levels, C-reactive protein concentration and white blood cells count. Finally, we assessed the associations between plasma level of AOPP and serum concentrations of creatinine and urea, both of which showed a strong dependence on the chronological age of haemodialysed patients. Taken together, our results confirm the robust relationship between uraemia and oxidative stress, especially when measured as biomarkers of severe protein oxidative damage (e.g. plasma AOPP).