Syringic acid Attenuates Oxidative Stress in Plasma and Peripheral Blood Mononuclear Cells of Patients with Acute Myeloid Leukemia.

Syringic acid (SA) is a natural phenolic acid that possesses antioxidant properties. The current study aimed to assess the possible ameliorative effects of SA on oxidative stress in patients with acute myeloid leukemia (AML). Twenty-two healthy donors as well as 22 sex- and age-matched AML patients participated in the study. AML patients were at the time of diagnosis and before remission. The peripheral blood mononuclear cells (PBMCs) and plasma samples were obtained and divided into four groups. The groups include: 1) buffer (B), containing isotonic phosphate buffer saline (100 mM, pH 7.4, 1 hr); 2) OX, containing solution subjected to iron-mediated oxidation (2.7 µM, 1 hr); 3) SA, containing SA solution (10 µM, 1 h) as ROS quencher and 4) SA + OX in which samples were pretreated with 10 µM of SA for 1 h, and then exposed to OX solution (2.7 µM) for 1 h. The results indicated that SA caused a significant increase in the activity of glutathione peroxidase (GPX) in PBMCs. Of note, the treatment of PBMCs and plasma samples of AML patients with SA was able to normalize the altered levels of GPX, superoxide dismutase (SOD), and catalase (CAT). The antioxidant effect of SA was further confirmed by analyzing the total oxidant status, lipid peroxidation, and protein carbonylation in both plasma samples and PBMCs of AML patients. According to the results, it seems that SA has strong protective effects on oxidative stress by elevating the total antioxidant status (TAS) of PBMCs and plasma specimens from AML patients.

Conformational changes of ß-thalassemia major hemoglobin and oxidative status of plasma after in vitro exposure to extremely low-frequency electromagnetic fields: An artificial neural network analysis.

Electromagnetic fields (EMF) can generate reactive oxygen species and induce oxidative modifications. We investigated the effects of extremely low-frequency electromagnetic fields (ELF-EMF) on oxidative status of plasma and erythrocytes in ß-thalassemia major patients and design artificial neural networks (ANN) for evaluating the oxyHb concentration. Blood samples were obtained from age and sex-matched healthy donors (n = 12) and major ß-thalassemia patients (n = 12) and subjected to 0.5 and 1 mT and 50 Hz of EMF. Plasma oxidative status was estimated after 1 and 2 h exposure to ELE-EMF. Structural changes of plasma proteins were investigated by Native PAGE and SDS-PAGE. Moreover; multilayer perceptron (MLP) method was applied for designing a feed forward ANN model to predict the impact of these oxidative and antioxidative parameters on oxyHb concentration. Two hour exposure to ELF-EMF induced significant oxidative changes on major ß-thalassemia samplesElectrophoretic profiles showed two high molecular weight (HMW) protein aggregates in plasma samples from healthy donors and major ß-thalassemia patients. According to our ANN design, the main predictors of oxyHb concentration were optical density of Hb at 542, 340, 569, 630, 577, and 420 nm and metHb and hemichrome (HC) concentration. Accuracy of the proposed ANN model was shown by predicted by observed chart (y = 1.3 + 0.96x, R2 = 0.942), sum of squares errors (SSR), and relative errors (RE). Our results showed the detailed effects of ELF-EMF on Hb structure and oxidative balance of plasma in major ß-thalassemia patients and significance of ANN analysis during normal and pathologic conditions.

Effect of alpha-lipoic acid supplementation on the lipid profile and lipid ratios in women with gestational diabetes mellitus: A clinical trial study.

BACKGROUND: Evidence suggests that Oxidative stress has been shown to plays an important role in gestational diabetes mellitus (GDM) etiology. On the other hand, women with GDM are at an increased risk for complications such as endothelial dysfunction and cardiovascular diseases. OBJECTIVE: To investigate the effects of alpha-lipoic acid (ALA) on the maternal circulating values of lipid profile and lipid ratios in women with GDM. MATERIALS AND METHODS: Sixty women with GDM were participated in the present study. The ALA group (n = 30) received ALA (100 mg/day) and the placebo group (n = 30) received cellulose acetate (100 mg/day) for eight wk. The maternal circulating values of hemoglobin A1C, triglyceride (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, triglyceride-glucose (TyG) index, atherogenic index of plasma (AIP), non-HDL-C, and lipid ratios were assessed before and after the intervention. P-value < 0.05 was considered as statistically significant. RESULTS: The values of TyG index (p < 0.001), TG (p = 0.006), TG/HDL-C (p = 0.003), and AIP (p = 0.005) decreased significantly in the ALA group after the intervention. CONCLUSION: Maternal circulating values of TyG index, TG, TG/HDL, AIP decreased after eight wk of ALA supplementation in women with GDM.

Protective properties of Myrtus communis extract against oxidative effects of extremely low-frequency magnetic fields on rat plasma and hemoglobin.

PURPOSE: This study investigates the protective properties of Myrtus communis extract against the oxidative effects of extremely low-frequency magnetic fields (ELFMF). Also, this study is aimed to analyze the conformational changes of hemoglobin, oxidative damages to plasma proteins and antioxidant power of plasma following exposure to ELFMF. MATERIALS AND METHODS: Adult male rats were divided into 3 groups: (1) control, (2) ELFMF exposure, and (3) ELFMF exposure after M. communis extract administration. The magnetic field (0.7 mT, 50 Hz) was produced by a Helmholtz coil for one month, 2 hours a day. The M. communis extract was injected intraperitoneally at a dose of 0.5 mg/kg before exposure to ELFMF. The oxidative effects of ELFMF were studied by evaluating the hemoglobin, methemoglobin (metHb) and hemichrome levels, absorption spectrum of hemoglobin (200-700 nm), oxidative damage to plasma proteins by measuring protein carbonyl (PCO) levels and plasma antioxidant power according to the ferric reducing ability of plasma (FRAP). The mean and standard errors of the mean were determined for each group. One-way ANOVA analysis was used to compare the means of groups. The significance level was considered to be p < .05. Moreover, artificial neural network (ANN) analysis was used to identify the predictive parameters for estimating the oxyhemoglobin (oxyHb) concentration. RESULTS: Exposure to ELFMF decreased the FRAP which was in concomitant with a significant increase in plasma PCO, metHb and hemichrome concentrations (p < .001). Oxidative modifications of Hb were shown by reduction in optical density at 340 nm (globin-heme interaction) and 420 nm (heme-heme interaction). Administration of M. communis extract increased FRAP values and decreased plasma POC, metHb, and hemichrome concentrations. Also, a significant increase in Hb absorbance at 340, 420, 542, and 577 nm showed the protective properties of M. communis extract against ELFMF-induced oxidative stress in erythrocytes. ANN analysis showed that optical absorption of hemoglobin at 520, 577, 542, and 630 nm and concentration of metHb and hemichrome were the most important parameters in predicting the oxyHb concentration. CONCLUSIONS: Myrtus communis extract enhances the ability of erythrocytes and plasma to deal with oxidative conditions during exposure to ELFMF. Also, ANN analysis can predict the most important parameters in relation to Hb structure during oxidative stress.

Effects of coenzyme Q10 supplementation on the serum levels of amylase, adenosine deaminase, catalase, and total antioxidant capacity in women with type 2 diabetes mellitus: A randomized, double-blind placebo-controlled trial.

BACKGROUND: Increased levels of reactive oxygen species is a key factor involved in the pathogenesis of type 2 diabetes mellitus (T2DM). Coenzyme Q10 (CoQ10) is a nonenzymatic antioxidant that restores other antioxidants. MATERIALS AND METHODS: This randomized, double-blind placebo-controlled trial study has been designed to evaluate the effects of CoQ10 supplementation on serum values of amylase, adenosine deaminase, catalase (CAT), total antioxidant capacity (TAC) and the quantitative insulin sensitivity check index (QUICKI) in women with T2DM. Serum levels of CoQ10 were measured too. Sixty-eight women with T2DM were enrolled in this study and randomly divided into two groups. One group received 100 mg/day of CoQ10 supplement for 12 weeks (n = 34), and the other group was given placebo for the same time duration and dosage (n = 34). RESULTS: After the intervention, serum CAT activity (P < 0.001), TAC (P = 0.006), CoQ10 (P = 0.001), and QUICKI (P = 0.005) increased and fasting blood sugar (FBS) (P = 0.05) decreased significantly in CoQ10 group. CONCLUSION: This study showed that daily supplementation with 100 mg of CoQ10 could increase TAC and CAT activity as, CoQ10 and QUICKI and could reduce oxidative stress and FBS in women with T2DM.

Effect of Omegaven on mast cell concentration in diabetic wound healing.

Diabetic wound healing is a complicated process. In all over the world 15% of 200 million diabetic people suffer from diabetic foot problems. Mast cells are known to participate in three phases of wound healing: the inflammatory reaction, angiogenesis and extracellular-matrix reabsorption. The inflammatory reaction is mediated by released histamine and arachidonic acid metabolites. Omega-3 fatty acids alter proinflammatory cytokine production during wound healing which affects the presence of inflammatory cells in wound area as well, but how this events specifically influences the presence of mast cells in wound healing is not clearly understood. This study is conducted to determine the effect of Omegaven, eicosapentaenoic (EPA) and docosahexaenoic (DHA) on pattern of presence of mast cells in diabetic wound area. Diabetic male wistar rats were euthanized at 1, 3, 5, 7 and 15 days after the excision was made. To estimate the number of mast cells histological sections were provided from wound area and stained with toluidine blue. In this relation wound area (8400 microscopic field, 45.69 mm2) were examined by stereological methods by light microscope. We found that comparing experimental and control group, omega-3 fatty acids significantly decreased wound area in day 7 and also the number of grade three mast cells in day 3 and 5. We also found that wound strength has significantly increased in experimental group at day 15.

Omegaven Improves Skin Morphometric Indices in Diabetic Rat Model Wound Healing.

The global prevalence of diabetes is estimated to be 200 million people, and it is likely to increase to 333 million people by 2025. Different cells, are known to participate in three main phases of wound healing. Omega-3 fatty acids influence cytokines and growth factors which affects the presence of inflammatory cells in wound area as well, but how this event specifically influences the role of fibroblasts, macrophages and angiogenesis in wound healing is not obviously understood. In this experimental study seventy male Wistar rats after induction of diabetes type-one by streptozotocin (STZ) (55 mg/kg) were divided into two groups, Experimental group receiving omegaven intraperitoneally and control group which underwent the injection of mineral oil. Streptozotocin was used for the induction of diabetes type 1. Diabetic male wistar rats were scarified at 1, 3, 5, 7 and 15 days after the excision was made. To estimate orphometric indices, histological sections were provided by stereological methods. It was found that wound area significantly decreased on day 7 in experimental group by omega-3 fatty acids. The number of fibroblasts increased significantly on days 5 and 7 in the experimental group. The number of neovascular significantly decreased on day 7 in the experimental group. This study implied that it seems omegaven is able to improve morphometric indices during wound healing and make healing faster.

Influence of Electromagnetic Fields on Lead Toxicity: A Study of Conformational Changes in Human Blood Proteins.

BACKGROUND: Electromagnetic fields (EMF) are associated with oxidative stress, which is in turn associated with reactive oxygen species (ROS), anemia, and hypoxia. OBJECTIVES: This study focused on the synergistic effects of lead ions and EMF on oxidative modifications in hemoglobin (Hb) and plasma proteins. PATIENTS AND METHODS: In this experimental study, the blood samples were obtained from age- and sex-matched healthy subjects at Arak University of Medical Sciences, Arak, Iran. The collected bloods were prepared as 55 samples and then divided into different groups for incubating with 0 to 100 uM of lead ions in 2 mT and 50 Hz of EMF for 120 minutes. The carbonyl group was determined to be an oxidative biomarker in plasma proteins. The ferric reducing ability of plasma (FRAP) was considered to be an antioxidant power of human plasma. The conformational changes in hemoglobin, met-Hb, and hemichrome were considered to be oxidative markers in red blood cells. To predict the factors affecting the oxyHb, the artificial neural network (MLP: 11,2,2,1) in SPSS software was applied. RESULTS: The test subjects showed increased concentrations of metHb (1.8 ± 0.19 vs. 1.36 ± 0.25) and hemichrome (6.01 ± 0.57) in relation to the control subjects. The decreased absorbance at 340 nm (0.88 ± 0.09 vs. 1.07 ± 0.08) demonstrated the reduced interaction between the globin chain and the heme ring. The decreased absorbance at 420 nm (Soret band) (2.96 ± 0.13) and the increased absorbance at 630 nm (0.07 ± 0.002 vs. 0.064 ± 0.005) indicated the conversion of oxyHb to metHb, which confirmed the oxidative damage to the erythrocytes. The linear regression analysis showed significant positive correlations between lead concentration and the percentage of plasma carbonyl content (R2 = 0.96), the relation of plasma carbonyl content to Hb absorbance at 630 nm (R2 = 0.97), and the relation of plasma carbonyl content to metHb concentration (R2 = 0.95) after 120 minutes incubation with lead ions in 20 millitesla and 50 hertz EMF. The artificial neural network analysis showed the significant importance of hemichrome, PCO, metHb, and lead concentration to the oxyHb content of erythrocytes. CONCLUSIONS: Lead contamination in the presence of an EMF exacerbates the oxidative damage to plasma proteins as well as the conformational changes in Hb. An artificial neural network can be used as a predictive tool for the oxidative danger posed to workers in industrial fields, battery manufacturing companies, and power plants.

Quantitative analysis for estimating injury effects of metal-catalyzed oxidation on human erythrocytes.

OBJECTIVE: To investigate whether human erythrocyte proteins were susceptible to oxidative effects of pharmacological doses of iron and whether resulting damages affect their structure. METHODS: Conformational changes in hemoglobin were indicated by spectrophotometric analysis from 300 to 650 nm. Carbonyl assay was performed for estimating the protein oxidation in erythrocytes. Oxidative injury in erythrocyte membrane was investigated by evaluation of the structural changes in cytoskeleton proteins by sodium dodecyl sulfate polyacrylamide gel electrophoresis in presence of 2-mercaptoethanol and staining with Coomassie briliant blue G-250. RESULTS: A significant increase in absorbance at 630 nm represented the formation of methemoglobin. Increase in absorbance at 340 nm was indicated by interaction between globin and heme group, which predicted for low oxygen affinity. A decrease in absorbance at 420 nm showed the conversion of oxygen hemoglobin to methemoglobin and significant decrease in oxygen hemoglobin concentration. There was marked elevation in hemichrome compared with control group. Of interest, a positive correlation was observed between iron concentration and hemoglobin absorbance at 340 nm. Elevated levels of carbonyl groups confirmed the oxidative damage to erythrocyte proteins. Analysis of membrane proteins using sodium dodecyl sulfate polyacrylamide gel electrophoresis, showed molecular aggregates in the range of 150 to 180 kDa and slight decrease in the intensity of α-spectrin band. CONCLUSIONS: It is possible to predict the situation of everyone who exposed to oxidant agent via a simple blood analysis. In this way, contents of oxidative products in blood samples would be assessed by this method.

Comparison of plasma oxidative biomarkers and conformational modifications of hemoglobin in patients with diabetes on hemodialysis.

BACKGROUND: Diabetes is associated with an increased generation of reactive oxygen species (ROS), which plays an important role in the development of oxidative stress and anemia. OBJECTIVES: The main purpose of this study was to investigate whether patients with diabetes undergoing hemodialysis (HD) were susceptible to oxidative stress and whether resulting damages affect the structure of hemoglobin (Hb) and plasma proteins. PATIENTS AND METHODS: Twenty patients with diabetes undergoing HD, 20 patients with diabetes and normal renal function, and 20 age- and sex-matched healthy subjects were included in this study. Methaemoglobin (Met-Hb), hemichrome and conformational changes of Hb were analyzed as oxidative markers in erythrocytes. Ferric reducing ability of plasma (FRAP) and protein carbonyl content (PCO) were determined as plasma oxidative biomarkers. Also triglyceride, cholesterol, albumin, blood urea nitrogen (BUN), creatinine, glucose and uric acid were assayed as biochemical parameters of plasma. RESULTS: Patients with diabetes undergoing hemodialysis had significantly lower levels of PCO and albumin (P < 0.05), but significantly higher levels of FRAP, BUN, creatinine and uric acid (P < 0.05) as compared to patients with diabetes and normal renal function. Linear regression analysis showed significant negative correlations between PCO and FRAP (r = -0.53), oxy-Hb (r = -0.88) and Hb absorbance at 340 nm (r = -0.79), 420 nm (r = -0.85) and 577 nm (r = -0.68) in patients with diabetes undergoing hemodialysis. Also PCO was significantly and positively correlated with Hb absorbance at 275 nm (r = 0.63) and 560 nm (r = 0.61) which confirmed the oxidative damage to erythrocytes in control subjects. CONCLUSIONS: Hemodialysis exacerbates oxidative stress and conformational changes of Hb in patients with diabetes on hemodialysis. The FRAP value can be used as a positive determinant, while PCO and Hb derivatives can be used as negative determinants of oxidative stress in patients with diabetes.