Sule Tamer

The benefits of hormone replacement therapy on plasma and platelet antioxidant status and fatty acid composition in healthy postmenopausal women

Oxidative stress is suggested to play an important role in the pathogenesis of cardiovascular disease (CVD). Various hormone replacement therapy (HRT) protocols are used to reduce the CVD risk in postmenopausal women. Recent studies found that HRT lowers lipid levels and improves vascular endothelial function in postmenopausal women. In this study the effects of HRT on plasma and platelet membrane fatty acid composition and the oxidant-antioxidant system in postmenopausal women are investigated. Blood samples were obtained from 50 postmenopausal women. Before starting treatment, all participants underwent clinical, biochemical and hormonal screening procedures including gynecologic and physical breast examination. Then oral HRT (2 mg estrodiol valerate + 1 mg cyproterone acetate) were given to all subjects for 1 year. Levels of malondialdehyde (MDA), total thiol (t-SH) and fatty acid contents, activities of glutathione-Stransferase (GST) and superoxide dismutase (SOD) were measured before and after treatment. Platelet membrane palmitic, stearic and oleic acid contents decreased (6.5%, 22.5% and 21.9% respectively) and linoleic and arachidonic acid contents increased (21.2% and 25.4% respectively) after HRT. Platelet MDA, GST and SOD levels were lower and t-SH content was higher than pre-treatment levels. These results indicate that hormone replacement therapy may affect platelet membrane fatty acid content and oxidant-antioxidant balance in postmenopausal women.

Oxidant–antioxidant profiles of platelet rich plasma in smokers

Cigarette smoke is a major risk factor for both coronary heart disease and peripheral vascular disease and has been reported to contain many oxidizing agents that lead to generation of free radicals. In this study, we investigated the levels of lipid peroxides (LPO) and antioxidant vitamins (C and E), total thiol content (t‐SH), the activities of superoxide dismutase (SOD), glutathione S‐transferase (GST) and glutathione peroxidase (GPx) in the platelet‐rich plasma (PRP) and plasma of 50 smokers and 30 non‐smokers. Total cholesterol (TC), low density‐cholesterol (LDL‐C), triglyceride (TG) and phospholipid (PL) levels of the plasma were significantly higher (p < 0.001) and high density‐cholesterol (HDL‐C) levels were significantly lower in smokers (p < 0.001) when compared with non‐smokers. In plasma and PRP, LPO levels, GST and SOD activities were found to be increased (p < 0.001) in smokers, whereas GPx activity, vitamin C levels and t‐SH content were found to be decreased. On the other hand, the levels of vitamin E was unchanged in plasma and PRP. The relationships between plasma levels of lipids, LPO and antioxidant systems were also investigated in both groups. A strong positive correlation was found between TC and Vit E (r = 0.5575; p < 0.001), LPO and PL (r = 0.4270; p < 0.01), LPO and GST (r = 0.3770; p < 0.01) and t‐SH and GPx (r = 0.3781; p < 0.01) in smokers. These findings reveal a disturbance of oxidant‐antioxidant balance by free radicals present in cigarette smoke, which may cause reduction in platelet hyperreactivity and endothelial dysfunction in smokers.

Identification of gene variants related to the nitric oxide pathway in patients with acute coronary syndrome

Dysfunction of vascular endothelium is known to have an essential role in the atherosclerotic process by releasing mediators including nitric oxide (NO). Nitric oxide maintains endothelial balance by controlling cellular processes of vascular smooth muscle cells. Evidence suggests that variations in the NO pathway could include atherosclerotic events. The objective of this study was to determine the possible effects of genes on the nitric oxide pathway in the development of acute coronary syndrome (ACS). The blood samples of 100 patients with ACS and 100 controls were collected at Istanbul University, Department of Cardiology. DNA samples were genotyped by using Illumina Cyto-SNP-12 BeadChip. The additive model and Correlation/Trend Test were selected for association analysis. Afterwards, a Q-Q graphic was drawn to compare expected and obtained values. A Manhattan plot was produced to display p-values that were generated by -log10(P) function for each SNP. The p-values under 1×10(-4) were selected as statistically significant SNPs while p-values under 5×10(-2) were considered as suspicious biomarker candidates. Nitric oxide pathway analysis was then used to find the single nucleotide polymorphisms (SNPs) related to ACS. As a result, death-associated protein kinase 3 (DAPK) (rs10426955) was found to be most statistically significant SNP. The most suspicious biomarker candidates associated with the nitric oxide pathway analysis were vascular endothelial growth factor A (VEGFA), methionine sulfoxide reductase A (MSRA), nitric oxide synthase 1 (NOS1), and GTP cyclohydrolase I (GCH-1). Further studies with large sample groups are necessary to clarify the exact role of nitric oxide in the development of disease.

Cyclosporin A-Associated Changes in Red Blood Cell Membrane Composition, Deformability, Blood and Plasma Viscosity in Rats

Most of the studies concerning the effects of cyclosporin A (Cs A) on red blood cell (RBC) rheology were carried out in human transplant recipients who may still have residual insufficiency and concomitant administration of other immunosuppressive and antihypertensive drugs. The aim of this study is to evaluate the effects of Cs A on red cell rheology and membrane composition in nontransplant healthy rats. Female Wistar albino rats were divided into two groups of 10 animals each. Rats received 10 mg/kg Cs A, i.p. or saline for 4 weeks. Cs A administration significantly increased the RBC deformability, and plasma and blood viscosity (p < 0.001, p < 0.01 and p < 0.01, respectively). Cs A administration to the rats increased RBC membrane cholesterol (CHO) levels and the CHO/phospholipid (PL) ratio significantly (p < 0.01 and p < 0.05, respectively) but did not change RBC membrane proteins and membrane PL levels. These results suggest that Cs A changes the rheological functions of RBC and lipid content of RBC membrane in healthy rats and thereby it may play an important role in the regulation of microcirculation.

Therapeutic Effects of Simvastatin on Galectin-3, and Oxidative Stress parameters in Lung Tissue in Endotoxemia

Galectins constitute of a soluble mammalian β-galactoside binding lectin family, which play homeostatic roles in the regulation of the cell cycle, and apoptosis, in addition to their inflammatory conditions. Galectin-3 has an important role in the regulation of various inflammatory conditions including endotoxemia, and airway inflammation. Statins, the key precursor inhibitors of 3-hydroxyl-3-methyl coenzyme A (HMG-CoA) reductase, may prevent the progression of inflammation in sepsis after prior statin treatment. Endotoxemia leads to the formation of oxidative stress parameters in proteins, carbohydrates, and DNA. In the present study, we aimed to show the effects of simvastatin on Galectin-3, and glutathione reductase (GR), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and thiobarbituric acid reactive substances (TBARS) levels in lung tissue of rats which were treated with lipopolysaccharides (LPS) during the early phase of sepsis. Rats were divided into four groups as the control, LPS (20 mg/kg), simvastatin (20 mg/kg), and simvastatin+LPS group. Galectin-3 expression in formalin-fixed paraffin-embedded lung tissue sections was demonstrated by using the immunohistochemistry methods. There were reduced densities, and the decreased number of Galectin-3 immunoreactivities in the simvastatin+LPS group compared with the LPS group in the pneumocytes, and in the bronchial epithelium of lung tissue. In the LPS group, GR, GSH-Px, and SOD were found lower than the levels in simvastatin-treated LPS group (P<0.05, P<0.01, P<0.01 respectively) in the lung tissue. However, TBARS decreased in the simvastatin+LPS group compared with the levels in LPS group (P<0.001). Simvastatin attenuates LPS-induced oxidative acute lung inflammation, oxidative stress, and suppresses LPS-induced Galectin-3 expression in the lung tissue.