Effects of vitamin C supplementation on oxidative stress and serum paraoxonase/arylesterase activities in patients on long-term hemodialysis / Efectos de la suplementación con vitamina C sobre el estrés oxidativo y las actividades de paraoxonasa/arilesterasa sérica en pacientes en hemodiálisis a largo plazo

Background: Oxidative stress increases oxidizability of apolipoprotein-B containing lipoproteins and decreases paraoxonase (PON) activity in hemodialysis (HD) patients and plays an important part in the development of atherosclerotic cardiovascular diseases. In HD patients, plasma ascorbic acid (AA) levels are decreased either due to the loss by hemodialysis membranes or due to malnutrition and contribute to the imbalance of antioxidant defense mechanisms. We hypothesized that long-term ascorbic acid (AA) supplementation recovers oxidizability of lipoproteins in HD patients by reinforcing PON activity. Methods: Twenty-nine adult patients were treated with 100mg and 500mg AA at the end of each HD session thrice a week for two consecutive 16 weeks-periods, respectively. Blood samples were obtained before the first HD session and prior to the first HD sessions following the 100mg AA-supplemented and the 500mg AA-supplemented periods. Results: PON activities were significantly increased after 100mg (p<0.05) and 500mg AA (p<0.001) supplementation periods compared to the basal level. Apo-B lipoprotein oxidizability (Δ-MDA) was significantly decreased after 500mg AA supplementation compared to both basal (p<0.05) and 100mg AA supplementation periods (p<0.05). Plasma AA concentrations were negatively correlated with Δ-MDA levels (R=−0.327; p<0.01). Conclusion: Our results suggest that long-term parenteral 500mg AA supplementation improves PON activity alleviating apo B-containing lipoproteins oxidizability in HD patients. (AU)

Antecedentes: El estrés oxidativo aumenta la susceptibilidad a la oxidación de las apolipoproteínas-B que contienen lipoproteínas y reduce la actividad de paraoxonasa (PON) en pacientes de hemodiálisis (HD) formando un papel importante en el desarrollo de enfermedades arterioescleróticas cardiovasculares. En pacientes de HD, los niveles de ácido ascórbico (AA) plasmático disminuyen debido a la pérdida por membranas de hemodiálisis o por desnutrición, y contribuye al desequilibrio de los mecanismos de defensa antioxidantes. Nuestra hipótesis es que a largo plazo la suplementación con AA recupera la susceptibilidad a la oxidación de las lipoproteínas en pacientes de HD al reforzar la actividad de PON. Métodos: Se trataron 29 pacientes adultos con 100 y 500mg de AA al final de cada sesión de HD/3 veces por semana/durante 2 períodos consecutivos de 16 semanas, respectivamente. Se obtuvieron muestras de sangre antes de la primera sesión de HD y previo a las primeras sesiones de HD luego de los 100mg suplementados con AA y los periodos suplementados con 500mg de AA. Resultados: Las actividades de PON aumentaron significativamente después de los periodos de suplementación de 100mg (p<0,05) y de 500mg de AA (p<0,001) comparados con el nivel base. La susceptibilidad a la oxidación de la lipoproteína apoB (Δ-MDA) disminuyó significativamente luego de la suplementación de 500mg de AA en comparación con períodos de valores base (p<0,05) y los de 100mg de AA (p<0,05). La correlación entre las concentraciones de plasma AA y los niveles de Δ-MDA resultó negativa (R=−0,327; p<0,01). Conclusión: Nuestros resultados sugieren que la suplementación parenteral a largo plazo de 500mg de AA mejora la actividad de PON mitigando la susceptibilidad a la oxidación de las lipoproteínas que contienen apoB en pacientes en HD. (AU)

Effects of vitamin C supplementation on oxidative stress and serum paraoxonase/arylesterase activities in patients on long-term hemodialysis.

BACKGROUND: Oxidative stress increases oxidizability of apolipoprotein-B containing lipoproteins and decreases paraoxonase (PON) activity in hemodialysis (HD) patients and plays an important part in the development of atherosclerotic cardiovascular diseases. In HD patients, plasma ascorbic acid (AA) levels are decreased either due to the loss by hemodialysis membranes or due to malnutrition and contribute to the imbalance of antioxidant defense mechanisms. We hypothesized that long-term ascorbic acid (AA) supplementation recovers oxidizability of lipoproteins in HD patients by reinforcing PON activity. METHODS: Twenty-nine adult patients were treated with 100mg and 500mg AA at the end of each HD session thrice a week for two consecutive 16 weeks-periods, respectively. Blood samples were obtained before the first HD session and prior to the first HD sessions following the 100mg AA-supplemented and the 500mg AA-supplemented periods. RESULTS: PON activities were significantly increased after 100mg (p<0.05) and 500mg AA (p<0.001) supplementation periods compared to the basal level. Apo-B lipoprotein oxidizability (Δ-MDA) was significantly decreased after 500mg AA supplementation compared to both basal (p<0.05) and 100mg AA supplementation periods (p<0.05). Plasma AA concentrations were negatively correlated with Δ-MDA levels (R=-0.327; p<0.01). CONCLUSION: Our results suggest that long-term parenteral 500mg AA supplementation improves PON activity alleviating apo B-containing lipoproteins oxidizability in HD patients.

A multicenter nationwide reference intervals study for common biochemical analytes in Turkey using Abbott analyzers.

BACKGROUND: A nationwide multicenter study was organized to establish reference intervals (RIs) in the Turkish population for 25 commonly tested biochemical analytes and to explore sources of variation in reference values, including regionality. METHODS: Blood samples were collected nationwide in 28 laboratories from the seven regions (≥400 samples/region, 3066 in all). The sera were collectively analyzed in Uludag University in Bursa using Abbott reagents and analyzer. Reference materials were used for standardization of test results. After secondary exclusion using the latent abnormal values exclusion method, RIs were derived by a parametric method employing the modified Box-Cox formula and compared with the RIs by the non-parametric method. Three-level nested ANOVA was used to evaluate variations among sexes, ages and regions. Associations between test results and age, body mass index (BMI) and region were determined by multiple regression analysis (MRA). RESULTS: By ANOVA, differences of reference values among seven regions were significant in none of the 25 analytes. Significant sex-related and age-related differences were observed for 10 and seven analytes, respectively. MRA revealed BMI-related changes in results for uric acid, glucose, triglycerides, high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase, and γ-glutamyltransferase. Their RIs were thus derived by applying stricter criteria excluding individuals with BMI >28 kg/m2. Ranges of RIs by non-parametric method were wider than those by parametric method especially for those analytes affected by BMI. CONCLUSIONS: With the lack of regional differences and the well-standardized status of test results, the RIs derived from this nationwide study can be used for the entire Turkish population.

Serum arylesterase activity is negatively correlated with inflammatory markers in patients with acute coronary syndromes.

OBJECTIVES: To examined whether serum paraoxonase (PON1) and arylesterase (ARE) activities are correlated with inflammatory biomarkers (procalcitonin and high sensitivity C-reactive protein (hs-CRP) in patients with acute coronary syndrome (ACS). METHODS: This cross-sectional study was conducted at the Departments of Cardiology and Biochemistry, Uludag University School of Medicine, Bursa, Turkey, from April 2007 to December 2007. Seventy-eight consecutive patients with ACS and 39 healthy controls were investigated. Acute coronary syndrome patients were divided into 3 groups according to their clinical presentation: unstable angina pectoris (UAP) (Braunwald III-B, n=25), non-ST elevation myocardial infarction (NSTEMI) (n=18), and ST-elevation myocardial infarction (STEMI) (n=35). Serum PON1/ARE activities were measured spectrophotometrically. Levels of procalcitonin and hs-CRP were measured by immunoassay. RESULTS: Paraoxonase/ARE activities were significantly lower in all patient groups compared to controls. No correlation between PON1/ARE activities and high-density-cholesterol levels was seen. Among ACS patients, serum ARE activity correlated inversely with baseline and 48-hour procalcitonin (r=-0.577, p=0.009, and r=-0.642, p=0.019) and hs-CRP levels (r=-0.614, p=0.03, and r=-0.719, p=0.044). CONCLUSION: Serum ARE activity is reduced in ACS patients and inversely correlated with inflammatory markers.

Association between paraoxonase 1 activity and severity of coronary artery disease in patients with acute coronary syndromes.

OBJECTIVE: We sought to investigate serum paraoxonase/arylesterase activities in patients with acute coronary syndromes (ACS) and their correlations with the severity and extent of coronary artery disease (CAD). METHODS AND RESULTS: Three groups of patients were investigated: 89 patients with ACS, 54 patients with normal coronary angiograms (no-CAD group), and 27 healthy comparison subjects. ACS patients were divided into three groups according to their clinical presentation: unstable angina pectoris (UAP, Braunwald III-B, n = 31), non-ST elevation myocardial infarction (NSTEMI) (n = 27), and ST-elevation myocardial infarction (STEMI) (n = 31). Serum paraoxonase/arylesterase activities were measured spectrophotometrically. Angiographic CAD extent was expressed both by the number of vessels diseased and by the Gensini scoring system. Results showed that serum paraoxonase/ arylesterase activities and the paraoxonase/high density lipoprotein-cholesterol (HDL-C) ratio were significantly lower in the STEMI, NSTEMI, UAP groups than in no-CAD and control groups. Serum paraoxonase/arylesterase activities and paraoxonase/HDL-C ratio were reduced in patients with 2-vessel disease (VD) and 3-VD compared to the I-VD and no-CAD group (P < 0.001). In patients with ACS, the Gensini score correlated inversely with serum paraoxonase (r = -0.419, P < 0.001), arylesterase (r = -0.492, P < 0.0001), and the paraoxonase/HDL-C ratio (r = -0.377, P < 0.001). Serum arylesterase (r = 0.161, P = 0.03) and paraoxonase (r = 0.135, P = 0.002) activities were positively correlated with HDL-C levels. Serum arylesterase activity (P < 0.0001), gender (P = 0.0037), diabetes mellitus (P = 0.005) and LDL-C levels (P = 0.03) were independent predictors of CAD presence. CONCLUSIONS: Serum paraoxonase/arylesterase activities are reduced in ACS patients and inversely correlated with the severity of CAD.

Oxidative stress and ferritin levels in haemodialysis patients.

BACKGROUND: Increased oxidative stress (OS) and inflammation are associated with atherosclerotic coronary artery disease in haemodialysis (HD) patients. Ferritin may have other effects in addition to its role in storing intracellular iron. This study was performed to determine any relationships between markers of OS, nutrition and inflammation in HD patients with normal and high ferritin levels. METHODS: Our cohort comprised 34 maintenance dialysis patients on erythropoietin therapy and 22 healthy controls. HD patients were divided into two groups: 17 with normal (<800 ng/ml) and 17 with high (>800 ng/ml) ferritin levels, and we measured lipid profile, albumin, highly sensitive C-reactive protein (hsCRP), anti-oxidant enzymes [whole blood glutathione peroxidase (Gpx), serum superoxide dismutase (SOD), paraoxonase, arylestherase (AE) and total anti-oxidant status (TAOC)], anti-oxidants (vitamin C) and lipid peroxidation products [red blood cell malondialdehyde (RBC MDA)]. RESULTS: Compared with controls, the HD patients had higher serum urea, blood pressure, triglyceride, hsCRP, RBC MDA, SOD and TAOC values and lower albumin, low-density lipoprotein cholesterol, apolipoprotein AI, paraoxonase, AE and whole blood Gpx activities. Serum vitamin C, uric acid, apolipoprotein B, total- and high-density lipoprotein cholesterol, apolipoprotein B MDA, and lymphocyte levels in the HD patients with normal and high ferritin levels were similar. The OS markers of HD patients did not differ, whether or not they received intravenous iron supplementation or had transferrin saturations < 50% or > or = 50%. CONCLUSION: HD patients are in a higher oxidative state, which results in the reduction of total anti-oxidant capacity and also have an increased inflammation status. We could not find a relationship between ferritin level and OS markers in HD patients receiving erythropoietin.

Major depressive disorder is accompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative-antioxidative systems.

OBJECTIVE: The aim of the present study was to investigate the oxidative-antioxidative systems and effects of different antidepressants on these systems in patients with major depressive disorder (MDD). METHOD: Ninety-six patients with a Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) diagnosis of MDD and 54 healthy controls were included in the study. Plasma malondialdehyde (MDA) levels and susceptibility of red blood cells (RBCs) to oxidation were determined to investigate the oxidative status, plasma vitamin E, vitamin C, serum total carotenoid levels, total antioxidant capacity (TAOC), RBC superoxide dismutase (SOD) and whole blood glutathione peroxidase (GPx) activities were measured to investigate the antioxidative defence before and after 6 weeks of antidepressant treatment. RESULTS: Plasma MDA levels and susceptibility of RBCs to oxidation were significantly higher in the MDD group compared with the control group. RBC SOD activity was significantly increased in patients with MDD, and furthermore there was a significant positive correlation between the severity of the disease and SOD activity. CONCLUSION: MDD is accompanied with oxidative stress; however, oxidative-antioxidative systems do not seem to be affected by 6 weeks of antidepressant treatment.