Search

Receptor for advanced glycation end-products (RAGE) is involved in the pathogenesis of diabetic nephropathy. FPS-ZM1, a selective RAGE inhibitor, in combination with valsartan were investigated for their protective potentials on the renal markers of tubular injury in streptozotocin-induced diabetic rats. Rats were assigned into groups of receiving FPS-ZM1 (1 mg/kg/day), valsartan (100 mg/kg/day), and FPS-ZM1 plus valsartan (1 mg/kg/day and 100 mg/kg/day, respectively) for one month. Kidney histology, renal inflammation and oxidative stress, and renal and urinary markers of tubular injury were investigated. FPS-ZM1 and valsartan in combination more significantly attenuated renal expressions of tumor necrosis factor-alpha and interleukin-6 genes and reduced urinary levels of interleukin-6. Moreover, the combination elevated renal NAD+/NADH ratios and Sirt1 activities, and mitigated nuclear acetylated NF-κB p65 levels. In addition to alleviating indices of oxidative stress i.e. malondialdehyde, superoxide dismutase and glutathione peroxidase, the combination of FPS-ZM1 and valsartan more effectively upregulated the renal levels of master antioxidant proteins Nrf2, heme oxygenase-1, and NAD(P)H:quinone oxidoreductase-1. Additionally, this dual therapy ameliorated more efficiently the indices of renal tubular injuries as indicated by decreased renal kidney injury molecule-1 levels as well as reduced urinary levels of cystatin C, retinol binding protein, and beta-2-microglobulin. While FPS-ZM1 alone had no appreciable effects on the renal fibrosis, the combination treatment ameliorated fibrosis better than valsartan in the kidneys. Collectively, these findings underline the extra benefits of FPS-ZM1 and valsartan dual administrations in obviating the renal tubular cell injury in streptozotocin-induced diabetic rats partly by suppressing renal inflammation and oxidative stress.

Summary Aim: Atherosclerotic lesions in the carotid arteries lead to a broad range of cerebrovascular disorders such as vascular dementia and ischaemic stroke. Recent studies have verified the beneficial role of atorvastatin (AV) in atherosclerosis. Despite a large body of studies, the mechanisms underlying this effect have not been completely explained. In this study, several experiments were performed on atherosclerotic rat models to investigate the anti-inflammatory and anti-apoptotic effect of AV in the carotid artery. Methods: In this experimental study, 40 male Wistar rats (250 ± 25 g) were randomly divided into four groups: rats on a normal diet (ND; n = 10); a high-cholesterol diet (HD; n = 10); a high-cholesterol diet plus AV (HD + AV; n = 10); and the AV control group (AV; n = 10). Cleavage of caspase-3 protein, expression of B-cell lymphoma 2 (Bcl-2) as well as phosphorylation of p38 mitogen-activated protein kinase (MAPK) were determined by immunoblotting assay in the carotid artery homogenate. Plasma atherogenic indices, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured by colorimetric assay at the end of the experiment. Plasma levels of oxidised LDL (oxLDL) were measured by sandwich enzyme-linked immunosorbent assay (ELISA). Results: After eight weeks of feeding with a high-cholesterol diet, an elevated level of oxLDL was observed in the plasma in the HD group compared with the ND group [214.42 ± 17.46 vs 69.13 ± 9.92 mg/dl (5.55 ± 0.45 vs 1.78 ± 0.26 mmol/l); p < 0.01]. AV administration significantly reduced oxLDL levels in the HD + AV compared to the HD group [126.52 ± 9.46 vs 214.42 ± 17.46 mg/dl (3.28 ± 0.25 vs 5.55 ± 0.45 mmol/l); p < 0.01]. Results also showed that compared with the HC group, the HC + AV group had lower levels of p38 phosphorylation (p < 0.05) and higher levels of Bcl-2 expression (p < 0.05). Lower levels of cleaved caspase-3 were observed in the HC + AV group in comparison with the HC group (p < 0.05). Conclusions: The resultant data suggest that the anti-apoptotic effect of AV could be partially mediated by the pro-inflammatory protein p38 MAPK and the anti-apoptotic protein Bcl-2 in the rat carotid artery. Atorvastatin can therefore be considered a target drug in the prevention or development of atherosclerotic events.

Background: Rheumatoid arthritis (RA) is one of most important collagen vascular diseases. It has an unknown origin. Objectives: The aim of this study was to evaluate circulating levels of osteoprotegerin (OPG), total soluble receptor activator of nuclear factor-Kappa B ligand (total sRANKL), and OPG/RANKL ratio in patients with RA. Methods: Forty-five females with RA, who fulfilled the American college of rheumatology (ACR) criteria for RA were included in this cross-sectional study. The overall disease activity was evaluated by the disease activity score based on 28 joint counts (DAS-28). The OPG and sRANKL were measured by the enzyme-linked immunosorbent assays (ELISA). The levels of high sensitive C-reactive protein (hsCRP) were measured by ELISA. We used Pearson's correlation for our comparisons. Results: There was no statistically significant dierence between the levels of hsCRP, OPG, sRANKL and RANKL/OPG ratio in terms of DAS; 28 grades in our patients.No significant correlation was found between the serum levels of OPG and DAS-28 (P = 0.525), duration of the disease (P = 0.884), Z score of the femur (P = 0.546) and Z score of the spine (P = 0.492), T score of the femur (P = 0.137) and T score of the spine (P = 0.821) in the patient group. No significant correlations were found between sRANKL levels with DAS-28 (0.919), Z score of the femur (P = 0.971), Z score of the spine (P = 0.832) and T score of the femur (P = 0170) in the studied groups. Conclusions: Our study showed that there was no significant correlation between hsCRP, OPG, sRANKL and RANKL/OPG ratio in DAS-28 grading of our patients. For this reason they will not be used for evaluating disease activity. However, there was a significant dierence between case and control groups except for sRANKL (pg/mL).

Introduction: Nephrotoxicity as a side effect caused by the immunosuppressive drug, cyclosporine-A (CsA), can be a major problem in transplant medicine. Oxidative stress may play an important role in the CsA-induced nephrotoxicity. It has been shown that the antihypertensive drug, valsartan (Val), has also renoprotective effects but, its molecular mechanism is largely unknown. In the present study, it was aimed to evaluate the Val effect in the alleviation of CsA nephrotoxicity via probable renal glutathione peroxidase (GPx) upregulation and oxidative stress decrease. Methods: Thirty-two Sprague-Dawley rats were divided into four groups based on CsA and/or Val administration: group A (Control, 1 mL/kg/day of olive oil as vehicle), group B (CsA, 30 mg/kg/day), group C (CsA+Val, 30+30 mg/kg/day), and group D (Val, 30 mg/kg/day). After the administration period (six weeks), renal GPx expression was evaluated by real-time polymerase chain reaction (PCR). Plasma levels of GPx and 8-Hydroxydeoxyguanosine (8-OHdG) were measured by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA) and protein carbonyl groups (PCG) were measured by spectrophotometer. Plasma levels of urea and creatinine were measured by an autoanalyzer. Results: CsA treatment led to the decrease in renal expression and plasma levels of GPx in comparison to other study groups. Rats received CsA were detected to have significantly (p

CONTEXT AND OBJECTIVE: Red grape seed extract (RGSE) contains oligomeric proanthocyanidin complexes as a class of flavonoids. These compounds are potent antioxidants and exert many health-promoting effects. This study aimed to determine the effects of RGSE on serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo-AI) levels and paraoxonase (PON) activity in patients with mild to moderate hyperlipidemia (MMH). DESIGN AND SETTINGS: A randomized double-blind placebo-controlled clinical trial was conducted at Shahid-Modarres Hospital (Tehran, Iran) and Tabriz University of Medical Sciences. Seventy MMH patients were randomly assigned to receive treatment (200 mg/day of RGSE) or placebo for eight weeks. RESULTS: Significant elevation in serum levels of apo-AI (P = 0.001), HDL-C (P = 0.001) and PON activity (P = 0.001) and marked decreases in concentrations of TC (P = 0.015), TG (P = 0.011) and LDL-C (P = 0.014) were found in the cases. PON activity was significantly correlated with apo-AI (r = 0.270; P < 0.01) and HDL-C (r = 0.45; P < 0.001). Significant differences between the RGSE and control groups (before and after treatment) for TC (P = 0.001), TG (P = 0.001), PON (P = 0.03), apo-AI (P = 0.001) and LDL-C (P = 0.002) were seen. CONCLUSION: It is possible that RGSE increases PON activity mostly through increasing HDL-C and apo-AI levels in MMH patients. It may thus have potential beneficial effects in preventing oxidative stress and atherosclerosis in these patients.

Introduction: There are many ideas concerning the etiology and pathogenesis of preeclampsia including endothelial dysfunction, inflammation and angiogenesis. Elevated levels of total homocysteine (Hcy) and lipoprotein (a) [Lp(a)] are risk factors for endothelial dysfunction. This study aimed to evaluate the effect of high dose folic acid (FA) on serum Hcy and Lp(a) concentrations with respect to methylenetetrahydrofolate reductase (MTHFR) polymorphisms 677C→T during pregnancy. Methods: In a prospective uncontrolled intervention, 90 pregnant women received 5 mg FA supplementation before pregnancy till 36th week of pregnancy. The MTHFR polymorphisms 677C→T, serum lactate dehydrogenase activity, urine protein and creatinine concentrations were measured before starting folic acid administration. Serum levels of Hcy and Lp(a) were determined before and after completion of folic acid supplementation period. Results: Supplementation of the patients with FA for 36 week decreased the median (minimum–maximum) levels of serum Hcy from 11.40 µmol/L (4.40-28.70) to 9.70 (1.60-20.80) µmol/L (p=0.001). There was no significant change in serum Lp(a) after FA supplementation (p=0.17). The overall prevalence of genotypes in pregnant women that were under study for MTHFR C677T polymorphism was 53.3% CC, 26.7% CT and 20.0% TT. There was no correlation between decreasing level of serum Hcy in the patients receiving FA and MTHFR polymorphisms. Conclusion: Although FA supplementation decreased serum levels of Hcy in different MTHFR genotypes, serum Lp(a) was not changed by FA supplements. Our data suggests that FA supplementation effects on serum Hcy is MTHFR genotype independent in pregnant women.

Introduction: The oxidative stress has been proposed as an important case of exudative age-related macular degeneration (E-ARMD). The aim of the present study was to investigate homocysteine (Hcy), asymmetric dimethylarginine (ADMA) and oxidized low-density lipoprotein cholesterol (Ox-LDL-C) levels, the factors involved in oxidative stress, in the patients with E-ARMD. Methods: In a cross-sectional study, 45 patients with E-ARMD were compared with 45 sex- and age-matched healthy controls. The levels of biochemical factors, Hcy, ADMA, and of Ox-LDL were estimated by standard methods in both study groups. Results: The levels of Hcy (15.4 ± 7.2 vs. 10.7 ± 3.7 μM, P = 0.001), Ox-LDL (52.2 ± 13.8 vs. 37.8 ± 10.8 U/l, P = 0.001), and ADMA (0.84 ± 0.23 vs. 0.71 ± 0.26 μM, P = 0.012) were significantly higher in the patients with E-ARMD than those in the controls. In the patient group, there was a positive and significant correlation between serum Ox-LDL and Hcy concentrations (r = 0.719, P = 0.001), but no correlation was found between serum ADMA and Ox-LDL (r = 0.010, P = 0.900) and also between serum Hcy and ADMA levels (r = -0.070, P = 0.600). Conclusion: The high levels of Hcy as an oxidant agent and ADMA as an endogenous nitric oxide synthase inhibitor can lead to increase Ox-LDL levels, and they may have important roles in oxidative stress, which can be a trigger in E-ARMD.

Oxidative stress and neuroinflammation are critically involved in amyloid beta (Aβ) induced cognitive impairments. β-Lapachone (β-LAP) is a natural activator of NAD(P)H quinone oxidoreductase 1 (NQO1) which has antioxidant and anti-inflammatory properties. This study investigated the effect of β-LAP administration on Aβ-induced memory deficit, oxidative stress, neuroinflammation, and apoptosis cell death in the hippocampus. Forty BALB/c mice were allocated into control, sham, β-LAP (βL), Aβ, and Aβ + βL groups. Intracerebroventricular injection of Aβ1-42 was used to induce Alzheimer’s disease (AD) model. Mice in the βL and Aβ + βL groups were treated with β-LAP (10 mg/kg, i.p) for 4 days. Results revealed that β-LAP attenuated memory impairment in the Aβ-received mice, as measured in the novel object recognition (NOR) and Barnes maze tests. Moreover, Aβ resulted in inflammasome activation evident by enhanced caspase-1 immunoreactivity and interleukin-1 beta (IL-1β) protein levels. However, β-LAP could markedly reduce reactive oxygen species (ROS) production and down-regulate mRNA expression of NLRP3 inflammasome and protein levels of cleaved caspase 1 and IL-1β. Additionally, β-LAP-treated mice showed increased SIRT1 levels and NAD+/NADH ratio in the hippocampus. These results were followed by fewer number of TUNEL-positive cell, reduced hippocampal atrophy and neuronal loss in the hippocampal dentate gyrus (DG). These results indicated that the protective effect of β-LAP against AD-associated cognitive deficits is partially through its strong antioxidant and anti-inflammatory actions.

Empagliflozin, a SGLT-2 inhibitor, improves diabetic nephropathy through its pleiotropic anti-inflammatory effects. The present study aims to evaluate empagliflozin effects on renal and urinary levels of tubular epithelial cell injury markers in streptozotocin-induced diabetic rats. Empagliflozin at 10 mg/kg (p.o.) was administered for 4 weeks, beginning 8 weeks after induction of diabetes. Renal function as well as markers of renal tubular epithelial cell injury were assessed in kidney tissue homogenates and urine. Empagliflozin was able to ameliorate diabetes induced elevations in serum cystatin C levels. It also alleviated renal KIM-1/NGAL levels and urinary albumin, α-GST, and RBP excretions. In addition to decreasing urinary levels of cell cycle arrest indices i.e. TIMP-2 and IGFBP7, empagliflozin mitigated acetylated NF-κB levels in renal tissues of diabetic rats. As a whole, these findings reveal empagliflozin capability in improving diabetic nephropathy via ameliorating indices of renal inflammation, injury, and cell cycle arrest on streptozotocin-induced diabetic rats.

Objective: Pentraxin 3 (PTX3) and C-reactive protein (CRP) may be associated with development of diabetic vascular complications. In the current study we evaluated the relationship between PTX3 levels and the presence and severity of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). Furthermore, we compared the sensitivity and specificity of PTX3 and CRP for detection of CAD. Methods: In 275 T2DM patients, coronary angiography revealed CAD (stenosis ≥ 50% at least in one vessel) in 140 patients and 135 patients without CAD. Gensini score was used to assess the severity of CAD. Demographic parameters and biochemical characteristics were measured in all participants. Results: Log-transformed mean plasma PTX3 levels were higher in T2DM patients with CAD than in T2DM patients without CAD (2.42 ng/mL vs 1.98 ng/mL, p

The aim of the present study was to evaluate the osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B ligand (RANKL), oxidant, and antioxidant status in untreated active pulmonary tuberculosis patients (PTB). Serum was obtained from 42 patients with different forms of untreated active PTB and 41 healthy subjects, as the control group. The serum levels of OPG, RANKL, tumor necrosis factor alpha (TNFα), malondialdehyde (MDA), total antioxidant capacity (TAC), and the lipid profiles were determined using standard methods. Patients with PTB were detected to have significantly higher plasma MDA, TNFα, OPG, and RANKL levels, and lower TAC levels, when compared to the healthy controls(p

Hyperlipidemia can lead to atherosclerosis by lipoprotein deposition inside the vessel wall and oxidative stress induction that leads to the formation of atherosclerotic plaque. Oxidized low-density lipoprotein particles (Ox-LDL) have a key role in the pathogenesis of atherosclerosis. The lipid-lowering properties and antioxidants of the grape seed can be beneficial in atherosclerosis prevention. We conducted a randomized double-blind placebo-controlled crossover clinical trial. Fifty-two mildly hyperlipidemic individuals were divided into two groups that received either 200 mg/day of the red grape seed extract (RGSE) or placebo for 8 weeks. After an 8-week washout period, the groups were crossed over for another 8 weeks. Lipid profiles and Ox-LDL were measured at the beginning and the end of each phase. RGSE consumption reduced total cholesterol (-10.68±26.76 mg/dL, P=.015), LDL cholesterol (-9.66±23.92 mg/dL, P=.014), and Ox-LDL (-5.47±12.12 mg/dL, P=.008). While triglyceride and very low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased by RGSE, the changes were not statistically significant. RGSE consumption decreases Ox-LDL and has beneficial effects on lipid profile-consequently decreasing the risk of atherosclerosis and cardiovascular disorders-in mild hyperlipidemic individuals.

Serum receptor activator of nuclear factor-κ B ligand and osteoprotegrin are mediated to vascular calcification in the general population. Our knowledge is very sparse in hemodialysis and renal transplant patients. Receptor activator of nuclear factor-κ B ligand, osteoprotegrin, intact parathyroid hormone, calcium, and phosphorus were measured in blood samples of 45 hemodialysis and 45 age-matched renal transplant patients. Osteoprotegrin (P = 0.001) and intact parathyroid hormone (P = 0.001) levels in the hemodialysis patients were higher than the renal transplant recipients. Osteoprotegrin had positive correlation with duration of dialysis and age in the hemodialysis (r = 0.88, P = 0.001 and r = 0.34, P = 0.02, respectively) and renal transplant patients (r = 0.92, P = 0.001 and r = 0.46, P = 0.001, respectively). Hemodialysis patients have higher osteoprotegrin levels than the renal transplant recipients. It may act as a protective factor for renal osteodystrophy or only as a secondary phenomenon of advanced renal failure.

Objective The aim of the present study was to evaluate of Fetuin-A and Pentraxin3 (PTX3) as the main factors for vascular calcification and inflammation in hemodialysis (HD) and renal transplant (RT) patients. Method Serum was obtained from 45 stable chronic HD patients and 44 stable RT recipients. Biochemical factors, intact Parathormone, high-sensitive C-reactive protein (hsCRP), Fetuin-A and PTX3 levels were determined by standard methods. Results In the RT recipients PTX3 level was significantly higher than the HD patients [5.78(1.09–20.36) ng/mL vs. 1.65(0.24–7.89) ng/mL, p ≤ 0.001]. Serum Fetuin-A concentration was significantly higher in the HD compared to RT group [43.39(27.75–81.48) ng/mL vs. 38.76(22.26–89.07) ng/mL, p = 0.020]. hsCRP level was also higher in the HD than the RT group [2.90(0.1–8.50) mg/L vs. 1.1(0.1–7.9) mg/L, p = 0.003]. Conclusion Although our study shows that serum PTX3 is increased and Fetuin-A is decreased after successful RT, their direct role on atherosclerosis needs further studies in the future.

PURPOSE Disequilibrium between oxidative stress and antioxidant levels has been proposed as an important case of exudative age-related macular degeneration (AMD). The aim of the present study was to investigate homocysteine (Hcy) level and antioxidant paraoxonase 1 (PON1) activity within its phenotypes together with oxidized low-density lipoprotein (OX-LDL) levels in the patients with exudative AMD. METHODS Serum PON1 activity and plasma Hcy and OX-LDL levels were analyzed in 45 exudative AMD patients and compared with 45 healthy controls. Paraoxonase 1 activity was measured in serum using paraoxon and phenylacetate as substrates. The PON1 phenotype was determined using double-substrate method. Homocysteine and OX-LDL levels were determined by enzyme-linked immunosorbent assay method. RESULTS The distribution of PON1 phenotypes was significantly different between the patients with exudative AMD and control subjects (chi-square = 6.17, P = 0.01). AA phenotype with low activity was significantly more frequent in exudative AMD patients compared with healthy subjects (62.2% vs. 35.6%, respectively). Other phenotype frequencies in the patients compared with controls were as AB phenotype (intermediate activity) 28.9% versus 46.7% and BB phenotype (high activity) 8.9% versus 17.8%, respectively. Except in BB phenotype (P = 0.2), patients with AA and AB phenotypes had higher plasma Hcy levels in comparison to those of controls (P = 0.02 and P = 0.03, respectively). The mean OX-LDL levels, in all 3 phenotypes (P < 0.05), and OX-LDL/high-density lipoprotein ratio, in AA and AB phenotypes (P = 0.001, P = 0.1, respectively) but not in BB (P = 0.1), were significantly higher in the patients than controls. No significant differences in comparison of Hcy and OX-LDL levels between 3 PON1 phenotypes in both control (P = 0.6 for Hcy, P = 0.7 for OX-LDL) and patients (P = 0.8 for Hcy, P = 0.6 for OX-LDL) were found CONCLUSION Increased plasma OX-LDL levels and ratios of OX-LDL/high-density lipoprotein, as biomarkers of lipoprotein oxidative stress, higher levels of Hcy, as oxidant agent, and more common low or intermediate PON1 activity in patients with exudative AMD, compared with controls, indicate that PON1 activity is insufficient to explain the increased oxidative stress observed in exudative AMD.

Objectives: To investigate the effect of lovastatin therapy and withdrawal on paraoxonase 1 (PON1) and arylesterase (ARE) activities, and low-density lipoprotein cholesterol (LDL-C) susceptibility to oxidation in people with type 2 diabetic nephropathy (T2DN). Design and methods: Lovastatin (20 mg/day) was administered to 30 people with T2DN for 90 days and then withdrawn for 30 days. PON1 and ARE activities were measured by the spectrophotometric method. Susceptibility of LDL-C to oxidation was determined as the production of conjugated dienes. Results: After 90 days of lovastatin intervention, PON1 and ARE activities and LDL-C lag phase were significantly increased (p = 0.004, 0.002, and

Objective Soluble receptor activator of nuclear factor-kappa B ligand (sRANKL) to osteoprotegerin ratio is designated as a bone metabolism equation in many rheumatologic disorders and would be modified with fish oil (FO) supplementation. Design and methods Eighty-three females with rheumatoid arthritis were divided randomly to 40 and 43 patients treated with (1 g/day) or without FO for 3 months accompanied with conventional drugs, respectively. Osteoprotegerin, sRANKL, tumor necrosis factor alpha (TNFα) serum levels were measured before and after treatment. Results Serum levels of osteoprotegerin increased, although sRANKL, TNFα and sRANKL/osteoprotegerin ratio decreased with FO therapy. A significant positive correlation was observed between sRANKL/osteoprotegerin ratio and TNFα levels ( r = 0.327 , p = 0.040) in the FO-treated group. Conclusions FO could decrease the inflammatory response by lowering of serum TNFα levels and sRANKL/osteoprotegerin ratio.

Background High serum phosphate and fibroblast growth factor-23 (FGF-23) levels are well-recognized independent risk factors of mortality and morbidity in patients with chronic kidney diseases (CKDs). Sevelamer, as a phosphate chelating agent, reduces serum phosphate and FGF-23 levels produced by bone osteocytes. This study aimed to determine the best dose at which sevelamer could successfully reduce serum phosphate and FGF-23 levels in rat models of adenine-induced CKD. Methods CKD was induced using adenine. Healthy and CKD-induced rats were divided into 6 groups as follows: healthy controls; CKD controls; rats treated with 1%, 2%, and 3% sevelamer for CKDs; and healthy rats administered 3% sevelamer. Biochemical factors and serum FGF-23 levels were measured using spectrophotometry and enzyme-linked immunosorbent assay methods. Results Serum phosphate levels were best decreased in rats receiving 3% sevelamer in their diet (5.91±1.48 mg/dL vs. 8.09±1.70 mg/dL, P

BACKGROUND Pregnancy Associated Osteoporosis (PAO) can lead to serious difficulties such as fragility fractures, elongated back pain and height loss in affected women. Soluble Receptor Activator of Nuclear Factor-Kappa B ligand (sRANKL) to Osteoprotegerin (OPG) ratio is chosen as a bone metabolism equation in many bone diseases characterized by bone resorption, such as post-menopausal osteoporosis and would be modified with folic acid supplementation. This study was done to compare the effects of high dose (5mg/day) and low dose (0.5 mg/day) folic acid in the RANKL/OPG ratio and Tumor Necrosis Factorα (TNFα) concentration during pregnancy. METHODS Forty-five pregnant women who visited the AL-Zahra Hospital, Tabriz Iran, from September 2013 to November 2014 were assigned into two groups in this randomized, double-blind, clinical trial, included women who took 5 mg/day (group1) and who took 0.5 mg/day (Group 2) folic acid supplementation before pregnancy until 36th pregnancy. The biochemical variables in serum of pregnant women were measured before and at the end of the study. The study was registered in the Iranian Registry of Clinical Trials (IRCT) as ID, IRCT2013122315903N1. RESULTS OPG levels were significantly higher compared with the baseline value (P=0.008), although sRANKL (P

Objective. Lipoprotein a [Lp(a)] is a strong biochemical risk factor that predicts posttransplant atherosclerosis. In this study we measured the ankle to arm blood pressure index (AAI) as a predictor of clinical atherosclerosis and assessed its relationship to serum Lp(a) values among 60 renal transplant recipients. Materials and Methods. After measuring the AAI in a recumbent position, biochemical factors including cholestrol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and Lp(a) were measured by commercial kits in 60 renal transplant and 30 healthy subjects. Results were analyzed using SPSS. Results. Lp(a) concentrations were significantly higher among transplant recipients compared with the control group (P .05). AAI was similar between the kidney transplant recipients and controls, showing no significant correlation of Lp(a) concentration with AAI. Conclusion. Increased serum Lp(a) in renal transplant recipients, a potent biochemical risk factor for atherosclerosis, was not associated with abnormal AAI.

Aims: Following carnitine administration a decrease in plasma levels of triglyceride (TG) and increase in total high-density lipoprotein cholesterol (HDL-C) has been reported. Our hypothesis was that it also improves the HDL2/HDL3 ratio, symptomatic intradialytic hypotension, and anemia in hemodialysis (HD) patients. Methods: Forty HD patients with a mean (± SD) age of 53 ± 13 years were treated with 500 mg/day carnitine taken orally for 2 months. Patients were used as their own controls (before treatment). Lipid and lipoproteins were determined by Alcyon Abbott autoanalyzer. HDL subclasses were measured by magnesium precipitation after fractionation with dextran sulfate. Hemoglobin, hematocrit and serum albumin were measured by standard methods. The results were analyzed by SPSS 11.05. Results: We found a significant decrease in serum TG (2.22 ± 0.99 vs. 1.93 ± 1.07 mmol/l, p < 0.01) and VLDL-C (0.93 ± 0.36 vs. 0.81 ± 0.34 mmol/l, p = 0.01) and a marked increase in HDL-C (0.9 ± 0.16 vs. 1.06 ± 0.24 mmol/l, p < 0.05), HDL2-C (0.17 ± 0.06 vs. 0.27 ± 0.14 mmol/l, p < 0.05) and albumin (37 ± 4 vs. 42 ± 5 g/l, p = 0.01) levels. The serum levels of total cholesterol (4.61 ± 0.89 vs. 4.5 ± 0.95 mmol/l, p = 0.1), LDL-C (2.78 ± 0.85 vs. 2.6 ± 0.89 mmol/l, p > 0.05), HDL3-C (0.73 ± 0.1 vs. 0.79 ± 0.17 mmol/l, p > 0.05), hemoglobin, hematocrit, and intradialytic blood pressure did not change after the treatment. Conclusion: Treatment with 500 mg/day carnitine taken orally for 2 months reduces serum levels of TG and VLDL-C, and increases HDL-C, HDL2-C and albumin in HD patients.

Background: Endotheline-1 (ET-1), an endothelial mediator, influences on mineral metabolism; especially vascular calcification in uremic patients. Objectives: The aim of the present study was to evaluate of ET-1, high-sensitivity C-reactive protein (hs-CRP) and mineral metabolites as the main factors for vascular calcification and inflammation in hemodialysis (HD) patients. Patients and Methods: In this cross-sectional study, 46 chronic stable HD patients were selected from nephrology departments of Tabriz University of Medical Sciences affiliated hospitals and classified based on phosphorus (P), Ca-P product (Ca × P) and intact Parathyroid Hormone (iPTH) levels. We evaluated fasting serum ET-1and hs-CRP levels by the standard methods and compared with 46 healthy control subjects. Results: The levels of serum hs-CRP and ET-1 were significantly higher in the patient’s group compared with controls (4.40 ± 1.26 vs. 1.38 ± 1.61, P < 0.0001, and 2.31 ± 0.87 vs. 0.75 ± 0.48, P < 0.0001, respectively) and with regard to Ca × P product cut-off point (3.99 ± 0.78 vs. 5.33 ± 1.64, P < 0.0001, and 2 ± 0.73 vs. 3.04 ± 0.73, P < 0.0001 respectively). ET-1 was correlated significantly with hs-CRP level (r = 0.776, P < 0.0001). Serum P, Ca × P and iPTH levels directly and Ca indirectly were correlated with serum ET-1 in HD patients (r = 0.932, P < 0.0001, r = 0.766, P < 0.0001, r = 0.514, P < 0.0001, r = -0.538, P < 0.0001 respectively). Multiple regression analysis demonstrated that serum P were independently associated with ET-1 levels (β = 0.932, P < 0.0001). Conclusions: Serum P and iPTH levels were independently associated with ET-1 and those may play a role in development of endothelial dysfunction in chronic kidney disease.

Patients on maintenance hemodialysis (HD) face an increased risk of atherosclerosis, a crucial problem and the leading cause of cardiovascular morbidity and mortality. This study was designed to evaluate the effects of zinc supplementation on paraoxonase (PON) enzyme activity in patients on HD.This double-blind randomized controlled trial was conducted from June 2005 to June 2007. Sixty HD patients were enrolled and divided into two groups: treatment (case) and control. The treatment and control groups were treated with 100 mg/day zinc or placebo, respectively, for 2 months. Serum zinc concentration was measured by atomic absorption spectrophotometry. PON activity was evaluated by spectrophotometric method. Lipid profile was determined using commercial kits, and apolipoprotein AI (Apo-AI) and B (Apo-B) levels were measured by commercial immunoturbidimetric kits.In the case group, there was no significant change in the serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and Apo-B levels, while the serum levels of high-density lipoprotein (HDL), Apo-AI, and PON activity were significantly increased (p = 0.02). In the control group, although significant increases were observed in the serum levels of TC, TG, and Apo-B (p = 0.009, 0.019, and 0.001, respectively), the serum PON activity was significantly decreased (p = 0.025) and the serum levels of HDL, LDL, and Apo-AI were not changed. At the end of intervention period, the serum level of Apo-AI and PON activity were significantly higher in the case group.Zinc supplementation increased both the activity of PON and the serum level of Apo-AI in the HD patients.

Objectives This study was designed to determine the effects of zinc supplementation on oxidative stress in hemodialysis (HD) patients through evaluating total antioxidant capacity (TAC), whole blood glutathione peroxidase (GSH) level, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) level. Design and Setting Double-blinded randomized controlled trialfrom October 2006 to December 2007 at Tabriz Imam Khomeini Hospital. Subjects Sixty-five HD patients were randomly enrolled into 2 groups. Intervention Patients received placebo in group A and zinc (100 mg/day) in group B for 2 months. After a washout period for 2 months, the groups were crossed over and the study was continued for an additional 2 months. Main outcome measures Serum zinc concentration was measured using atomic absorption spectrophotometry. TAC, GSH level, and SOD activity were determined by commercial enzyme-linked immunosorbent assay kits. MDA level was measured using a thiobarbituric acid method. Results The levels of serum zinc, TAC, GSH ( P P P = .003 for group B) significantly increased after zinc supplementation whereas the serum level of MDA decreased after the same period ( P = .003 for group A and P Conclusions Zinc supplementation for 2 months improved the serum levels of zinc, antioxidant status, and lipid peroxidation in HD patients.

Objectives Tuberculosis remains one of the most common infectious diseases and a leading cause of mortality world wide. There is some evidence for the possible involvement of Mycobacterium tuberculosis in atherosclerosis. We aim to investigate total antioxidant capacity (TAC), red blood cell superoxide dismutase (SOD) activity, whole blood glutathione peroxidase (GPX) activity, low-density lipoprotein (LDL) susceptibility to oxidation, and malondialdehyde (MDA) levels in patients with pulmonary tuberculosis (PTB). Methods Forty-five males with active PTB (case group) and 45 healthy age-matched males (control group) were enrolled in the study. TAC, SOD and GPX activities were determined by commercial ELISA kits. MDA levels were measured using the thiobarbituric acid method. LDL susceptibility to oxidation was assessed by measuring lag phase duration. Results TAC, SOD and GPX activities, and lag phase duration in the case group were significantly lower than the control group ( p = .002, p = .004, p = .008, and p = .004, respectively; independent), while the MDA levels was higher in case group ( p = .024). Conclusions Our findings suggest a higher susceptibility of LDL to oxidation and higher levels of lipid peroxidation, and therefore, a possible higher risk of atherosclerosis in patients with PTB.

Purpose: The main aim of this study was to evaluate the inhibitory impacts of the aqueous extract of garlic (Ga) on the formation of cataract induced by sodium selenite (Se). Methods: Thirty-two Wistar albino rat pups (4 equal groups: G1, G2, G3, and G4) were treated as follows: G1, subcutaneous (s.c.) and intraperitoneal (i.p.) injection of normal saline (0.3 mL) on postpartum (day 10); G2, i.p. injection of aqueous extract of garlic (1 mL/kg body weight) and s.c. injection of normal saline (0.3 mL) on postpartum (day 10); G3, s.c. injection of sodium selenite (20 nmol/g body weight) and i.p. injection of normal saline (0.3 mL) on postpartum (day 10); and G4, s.c. injection of sodium selenite (20 nmol/g body weight) and i.p. injection of aqueous extract of garlic (1 mL/kg body weight) on postpartum (day 10). Daily i.p. injections of aqueous extract of garlic (in G2 and G4) and normal saline (in G1 and G3) were continued for 14 days. The development of cataract was assessed over a period of 2 weeks after injection of sodium selenite. For further examination, the rats’ lenses were removed and analyzed for glutathione (GSH), malondialdehyde (MDA) levels, and superoxide dismutase (SOD), glutathione peroxidase (GPX) activities. Results: In G3 (Se-treated group), all rats developed grade 3 cataract in both eyes. However, in G1 (untreated control group), G2 (Ga-treated group), and G4 (Ga–Se-treated group), the lenses in both eyes of all rats remained clear ( P < 0.0001). This clinical fi nding was associated with higher GSH level and GPX, SOD activities and lower level of MDA in the Se- and Ga-treated group (G4) compared with SS-treated group (G3) rat lenses ( P < 0.003). Conclusions: Intraperitoneal injection of the Ga in rat model appeared to effectively prevent Se-induced cataract, thus such herbal remedy may be considered for treatment of cataract.

Oxidative stress is the main mechanism resulting in cyclosporine-induced nephrotoxicity. Because of its ability to stimulate endogenous melatonin production, isoproterenol is one of the most powerful antioxidant drugs. In this study, we sought to determine the effect of isoproterenol on cyclosporine-induced nephrotoxicity in rats.Thirty two young male Wistar rats were divided into four groups: of group A were controls that received placebo; group B, received intraperitoneal isoproterenol (20 mg/kg/d) alone; group C, intravenous cyclosporine (15 mg/kg/d) alone; and group D, both drugs simultaneously at the same doses and durations namely cyclosporine 1 week after administration of isoproterenol. Blood samples to measure serum urea, creatinine, and melatonin levels were drawn four times for each group: before injection, at the mid period of treatment, at the end of treatment, and 1 week after the last injections.Isoproterenol increased mean serum melatonin level in groups B and D rats (P.05). With regard to deteriorated renal function [DRF = (urea + creatinine)/2], administration of cyclosporine with (group D) or without (group C) isoproterenol was associated with decreased renal function (P.05), although it was more perturbed in the latter instance. Measured DRF at the middle and the end of drug administration periods of A and B (revealed significant differences compared with groups C and D; P.05).Although cyclosporine-induced nephrotoxicity is not completely eliminated by isoproterenol, the latter showed some protective effects.

Fifty-four juvenile male New Zealand white rabbits were randomly allocated to 9 groups including chow-fed rabbits without mineral supplementation, HC diet fed rabbits without mineral supplementation, HC + Cu, HC + Zn, HC + FeO, HC + Cu + Zn, HC + FeO + Cu, HC + FeO + Zn, and HC + FeO + Cu + Zn. Feeding HC diet resulted in a significant (P.001) increase in the serum cholesterol, TG, LDL, and very LDL except HDL when compared with chow-fed rabbits. The highest serum lipid profiles were observed in the FeO rabbits without copper or zinc supplementation. A modest decrease in serum thiobarbituric acid reactant substances in rabbits given the HC + Zn was accompanied by a significant (P.05) increase in antioxidant enzymes activities excluding superoxide dismutase that was markedly lower than those given the HC + Cu (12.83 +/- 2.13 vs 16.00 +/- 2.23 U/mL serum). Supplementation with copper alone in both the FeO and the non-FeO rabbits significantly (P.001) enhanced serum ceruloplasmin activity in comparison with other groups, but co-supplementation of copper plus zinc in the non-FeO rabbits did not significantly (P.05) affect ceruloplasmin activity in comparison with those treated with unsupplemented regimens. A significant decrease was found in sudanophilia area of rabbits supplemented with zinc (62.36% +/- 3.55%) compared to those given the HC + FeO, the HC + FeO + Cu, and HC without mineral supplementation; however, no significant (P.05) difference in animals given the HC + Cu, the HC + Cu + Zn, and the HC + FeO + Zn was observed. Based on these findings, it may be suggested that the antiatherogenic effects of zinc in presence of copper, on which there is overloading of iron, is reduced under hypercholesterolemia.

In this study the effect of losartan and enalapril on the reduction of DNA damage was evaluated in regard to renin-angiotensin system (RAS) polymorphisms.After determination of genotypes of RAS polymorphism by PCR, 64 renal transplant recipients were randomly allocated to one of four groups: the first and second groups were treated with E (E+: 10 mg/day) and L (L+: 50 mg/day) alone, respectively. The third group received E+L (E+L+: 10 + 50 mg/day), and the forth group received no medication (E-L-). The subjects were followed for 8 weeks. After a 2-week washout period, the E group changed to L and vice versa as a cross-over design. They were followed for another 8 weeks. Before and after treatment, we checked 8-OHdG and malondialdehyde (MDA) as biomarkers of DNA damage and lipid peroxidation, respectively.8-OHdG levels were significantly decreased after treatment in the E+L+ and L+ groups (P0.001, P = 0.001, respectively). Only the TT genotype of AGT had the most antioxidative role regarding the treatment (P = 0.01). We found a remarkable correlation between MDA and DNA damage levels before and after intervention (r = 0.48, P0.001; r = 0.35, P = 0.006).The protective effects of L+ and E+L+ on DNA breaks are surprising regarding the RAS polymorphisms.

Objectives: In this study, the effect of enalapril (E) and/or losartan (L) on lipid peroxidation (LPO) is studied in renal transplant recipients (RTRs) with regard to polymorphisms of renin–angiotensin system (RAS). Design and methods: After determination of genotypes of the angiotensin-converting enzyme (ACE I/D), angiotensinogen (AGT M235T) and angiotensin II type 1 receptor (ATR1 A1166C) by PCR, sixty-four RTRs recruited to four groups randomly: first (13 patients) and second (20 patients) groups were treated with enalapril (E + : 10 mg/day) and losartan (L + : 50 mg/day) alone for 2 months, respectively. After 2 weeks as washout period, E group changed to L and vice versa as a cross-over design and they were treated for another 2 months. The third group (13 patients) as positive control received enalapril + losartan (E + L + : 10 mg/day + 50 mg/day) for 16 weeks, and the forth group (18 patients) as negative control received no medication (E − L − ). Malondialdehyde (MDA) as LPO marker was measured before and after treatment. In this study, P Results: After 2 months of treatment, MDA level significantly decreased in all of the groups except the E − L − . MDA level in pre- vs. post-intervention for the E + L + , E + , L + and E − L − groups were as follows: 5.81 ± 2.13 nmol/mL vs. 1.61 ± 0.80 nmol/mL ( P = 0.001), 5.10 ± 2.05 nmol/mL vs. 1.68 ± 1.01 nmol/mL ( P = 0.003), 5.20 ± 1.61 nmol/mL vs. 1.22 ± 0.27 nmol/mL ( P = 0.000) and 5.27 ± 2.12 nmol/mL vs. 5.07 ± 2.03 nmol/mL ( P = 0.52), respectively. Also, the same results were found in the end of 16th week. Although patients with DD genotype of ACE had higher MDA ( P = 0.01) levels, RAS polymorphisms could not predict the antioxidative response rate to the drugs ( P > 0.05). Conclusions: E and/or L reduce MDA regardless of the RAS genotypes.

This study was designed to determine the effect of nandrolone decanonate (ND) on HDL-C, apolipoproteins and paraoxonase (PON) activity in stable hemodialysis patients.64 hemodialysis patients were treated with ND at a dose of 100 mg/I.M./week for 4 months. HDL-C, Apo-AI, Apo B, concentrations and PON activity were measured before and after 2 and 4 months of treatment as well as 2 months after withdrawing the treatment.After 4 months of treatment, an elevation in the serum levels of Apo B (P0.0001) and a marked decrease in the concentration of HDL-C (P0.0001), Apo-AI (P0.0001) and PON activity (P0.0001) were found. A significant correlation between PON and both Apo-AI (r=0.270, P0.04) and HDL-C (r=0.455, P0.0001) and also between HDL-C and Apo-AI (r=0.305, P0.02) were found.Results revealed the adverse effects of ND on apolipoprotein levels in our study population. It is possible that ND reduces PON activity mostly by reducing both the HDL-C and Apo-AI levels.

Malnutrition, anemia and increased atherosclerosis are the main causes of mortality in hemodialysis patients. Therapies designed to improve the disorders might therefore be expected to improve outcome. The effects of Nandrolone Decanoate (ND), in 64 stable hemodialysis patients, were studied with respect to the following parameters: nutritional status, hematological indexes, lipid profiles including serum levels of lipoprotein(a) [Lp(a)] in terms of differences in apolipoprotein(a) [apo(a)]. The patients were treated with ND at dose of 100 mg/I.M./week for 4 months. After 2 and 4 months of treatment the elevations in the serum levels of albumin (p 30 mg/dl) than those of with low Lp(a) (

BackgroundImbalanced Matrix Gla protein (MGP) and Osteoprotegerin (OPG) levels occur in inflammatory diseases.Aim of the workThe aim of the present study was to evaluate serum MGP and OPG levels in Rheumatoid Arthritis (RA) patients and study their relation to the disease activity.Patients and methodsForty-five female RA patients and 45 age and sex-matched healthy controls were included in this study. Disease activity score 28-C-reactive protein (DAS28-CRP) was used for the assessment of disease activity. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), MGP and OPG were measured in patients and controls. The associations of MGP and OPG with DAS28-CRP and the other laboratory and clinical variables were analyzed.ResultsRA patients had significantly higher serum OPG levels (408.3±520.9pg/ml) and hs-CRP (2.8±1.9mg/l) than the control (92.5±86.3pg/ml and 0.9±1.5mg/l respectively) (p