Cahide Gokkusu

Changes of oxidative stress in various tissues by long-term administration of vitamin E in hypercholesterolemic rats

BACKGROUND Free radical-mediated oxidative stress has been implicated in the genesis and progression of atherosclerosis. METHODS The lipid peroxides and antioxidant status of various tissues were investigated in hypercholesterolemic rats and the effect of vitamin E supplementation on defense systems. RESULTS Cholesterol-feeding caused a significant increase in the lipid peroxide concentrations of plasma, erythrocytes, liver and brain. In addition, a significant decrease in glutathione (GSH) content, glutathione peroxidase (GSH-Px) and glutathione transferase (GSH-ST) activities were found in erythrocytes and liver but superoxide dismutase (SOD) activity remained unchanged in these tissues in comparison to the control group. Vitamin E supplementation to hypercholesterolemic rats induced a significantly decrease in lipid peroxide concentrations and a significant increase in the GSH content, GSH-Px and GSH-ST activities in erythrocytes and liver. CONCLUSIONS Long-term administration of vitamin E may play an important role in suppressing oxidative stress, and thus, may be useful for the prevention and/or early treatment of hypercholesterolemia.

Association of genetic variants in Methylenetetrahydrofolate Reductase and Paraoxonase-1 genes with homocysteine, folate and vitamin B12 in coronary artery disease

Background The aim of the present study was to investigate the association between genetic variants in metylenetetrahydrofolate reductase (MTHFR) and Paraoxonase-1 (PON1) 55/192 genes and total homocysteine (tHcy), folate, B12 vitamin, and PON1 levels in patients with coronary artery disease (CAD). Methods The study included 235 patients with CAD and 268 healthy control subjects. Results LL and LM genotypes and L allele of PON1 55 were over-represented in patients. In contrast, MM genotype and M allele were more frequent in controls. QQ genotype and Q allele of PON1 192 and CT genotype of MTHFR were significantly diminished and QR genotype and R allele were significantly elevated in CAD patients compared with controls. The plasma tHcy were elevated but B12 levels were diminished in patients. PON1 55 and 192 genetic variants were significantly associated with PON1 activity, triglyceride, total cholesterol, tHcy and, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol in patients, respectively. Conclusion Genetic variants of PON1 55/192 and MTHFR were associated with CAD.

Thymosin α1 protects liver and aorta from oxidative damage in atherosclerotic rabbits

Abstract The thymus hormones were reported to be effective on lipid peroxidation and the antioxidant system. Thymus plays a broader role than just regulating the immune system. Thymosin α1 is the first subgroup extracted from thymosin F5 and has higher biological activity than thymosin F5. In the present study, we have examined the effects of thymosin α1 on lipid levels and lipid peroxidation and glutathione (GSH) content in the plasma, liver and aorta tissues of atherosclerotic rabbits. At the end of thymosin α1 treatment, we determined the lipid levels and lipid peroxidation of the plasma, liver and aorta tissues and hepatic subcellular fractions in these rabbits. Our results demonstrated that thymosin α1 might normalize changed lipid levels and increased lipid peroxides and also elevate decreased GSH in the plasma, liver and aorta tissues of atherosclerotic rabbits. Results of this study suggest that thymosin a, may be beneficial to prevent and/or to treat atherosclerosis.

Influences of genetic variants in interleukin-15 gene and serum interleukin-15 levels on coronary heart disease

Interleukin-15 (IL-15) is a potent proinflammatory cytokine that is now considered a key component of atherosclerosis. Proinflammatory gene polymorphisms lead to variations in the production and level of the proteins. In light of these findings, we hypothesized that variations in the gene coding for IL-15 influence the risk of coronary heart disease (CHD) by modulating the IL-15 levels. To test this hypothesis, we examined 5 single nucleotide polymorphisms (SNPs) in IL-15 gene and IL-15 levels in 102 patients with acute coronary syndrome (ACS), 102 patients with chronic ischemic stable CHD and 162 healthy control subjects. This study is the first report showing the influences of IL-15 gene variants and IL-15 levels on CHD. The five single nucleotide polymorphisms (SNPs) within the IL-15 gene, G367A, C267T, A14035T, C13687A, and A10504G were carried out by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). Serum IL-15 levels were significantly higher in both acute and chronic patients than in controls. Genetic variants of IL-15 gene and IL-15 levels were associated with CHD. In conclusion, our study supports the hypothesis that genetic variation in IL-15 gene and IL-15 levels influence the risk of CHD. Further studies are needed to confirm our hypothesis.

Homocysteine and pro-inflammatory cytokine concentrations in acute heart disease

Inflammation is involved in development and progression of atherosclerosis. Interleukin-2 (IL-2) and interleukin-6 (IL-6) have been correlated with various cardiovascular diseases. Hyperhomocysteinemia is an important risk factor for atherosclerosis and thrombotic disease. Recent studies have demonstrated that homocysteine (Hcy) enhances productions of several pro-inflammatory cytokines. In the light of these findings, we decided to determine if any relationship exists between IL-2 and IL-6, the pro-inflammatory cytokines, and total homocysteine (tHcy) in acute coronary syndrome (ACS). A total of 102 patients with ACS and 90 healthy subjects were included in the study. The levels of tHcy, IL-2 and IL-6 were higher and folic acid was lower in patients as compared with those of controls. Furthermore, data of the area under ROC plot for IL-2 demonstrated that IL-2 had higher sensitivity. These data suggest that enhanced inflammation may be associated with tHcy-related cardiovascular disease.

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.

Vitamin E and ATPases: Protection of ATPase Activities by Vitamin E Supplementation in Various Tissues of Hypercholesterolemic Rats

It has been shown that the lipid composition of plasma membrane can be modified in vivo by dietary fat. It has also been observed that an increase in the cholesterol content of plasma membranes results in decreased activities of ATPases. In the present study, we evaluated the changes in the activities of ATPases from erythrocytes, hepatocytes, and kidney cortex caused by cholesterol-rich diet in rats and subsequently examined the role of vitamin E administration on the cholesterol-induced effects in these tissues. Administration of hypercholesterolemic diet to the rats for 4.5 months, significantly decreased membrane Na(+)-K(+)-ATPase and Ca+2-ATPase activities in comparison to the controls in all tissues studied. Vitamin E supplementation to the hypercholesterolemic rats led to a recovery in membrane ATPase activities. In conclusion, vitamin E supplementation to the rats provided protection against hypercholesterolemic diet-induced impairment of membrane-bound ATPases.

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.

The evaluation of lipid peroxidation and acute effect of octreotide on lipid peroxidation in patients with active acromegaly

BACKGROUND Although lipid peroxidation has been suggested to play a role in the etiology of many diseases, there is no report about its role in acromegaly in the literature. In the present study, we analyzed the basal levels of lipid peroxides (LPO) in newly diagnosed acromegalic patients, and to evaluate whether octreotide (OCT) has any effect on lipid peroxidation in these patients. METHODS Plasma lipid peroxide levels before and after acute OCT administration were measured in 12 newly diagnosed acromegalic patients. Blood samples were drawn at basal and 4, 8, and 24 h after octreotide injection (100 microg s.c.). Plasma concentrations of lipid peroxides were estimated from measurement of thiobarbituric acid reactive substance (TBARS), using 1,1,3,3-tetra-ethoxypropane as a standard. RESULTS This study shows that acromegalic patients have significantly higher basal plasma lipid peroxides levels compared to hours after OCT injection (p<0.001). Although a significant decrease was observed after 8 and 24 h in comparison to basal level (p<0.001), the lipid peroxide levels tended to increase at 24 h though still low when compared to basal level. CONCLUSION Acromegalic patients have high basal lipid peroxide levels, which was significantly decreased after OCT administration.

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.