Gülinnaz Alper

Effect of dietary vitamin E supplementation on vascular reactivity of thoracic aorta in streptozotocin-diabetic rats.

The present study evaluated the effect of dietary vitamin E supplementation (1,000 mg/kg chow) on the alterations in vascular reactivity of streptozotocin-diabetic aorta of Wistar rats. After 12 weeks of treatment, thoracic aortic rings of rats were mounted in organ baths and contractile responses to phenylephrine and 5-hydroxytryptamine and relaxant responses to acetylcholine, calcium ionophore and sodium nitroprusside were assessed. Plasma vitamin E concentration as measured by HPLC was markedly decreased in diabetic rats and increased with dietary vitamin E supplementation. Induction of diabetes significantly impaired endothelium-dependent relaxations to acetylcholine and calcium ionophore in aortic rings, but did not change endothelium-independent relaxation to sodium nitroprusside. Vitamin E significantly improved the impaired endothelium-dependent relaxations, further it decreased the enhanced contractile response to phenylephrine and 5-hydroxytryptamine in diabetic rings. The mechanical denudation of endothelium or the chemical inhibition of endothelium-dependent relaxation with Nω-nitro-L-arginine methyl ester (100 µmol/l) significantly increased phenylephrine contractility in control rings and the rings of diabetic rats treated with vitamin E; such a difference was not observed in diabetic rats fed with normal diet. Liver and lung malondialdehyde concentrations, as an index of lipid peroxidation, were increased in diabetic rats and significantly decreased with vitamin E supplementation. It is concluded that dietary supplementation of vitamin E improved endothelial dysfunction in insulin-dependent model of uncontrolled diabetes, probably decreasing membranal lipid peroxidation.

MAO inhibitors and oxidant stress in aging brain tissue

The process of aging presents itself with various alterations in physiological events. Among many theories, the free radical (FR) theory of aging which reflects the FR damage to cellular components is accepted as one of the most important theories. Recently, the increases in catecholamine metabolism in aging have also attracted attention, and monoamine oxidase (MAO), a key enzyme in this process has been extensively studied. The aim of this study was to assess the role of FR species via MAO, a possible source of FRs, in physiological aging by determining the lipid peroxidation products (LPP) (malondialdehyde, diene conjugates) and antioxidant enzyme levels (superoxide dismutase (SOD) and catalase (CAT) in young (3 months old, n=10) and aging (16-18 months old, n=10) rat brain tissues of Swiss male albino rats. In the second part of the study, the same parameters were determined after the acute administration of MAO inhibitors (deprenyl and pargyline, 25 mg/kg i.p.) to investigate whether these agents have any beneficial effects in reducing oxidant stress via inhibition of MAO. In old rat brains, MAO activities showed a significant increase (P=0.000) in addition to an insignificant increase in LPP, while SOD (P=0.007) and CAT activities showed a decrease with advancing age. After the acute administration of both deprenyl and pargyline, a significant decrease in the MAO activities of both young (P=0.0002 for each) and aging rats (P=0.0002 for deprenyl and P=0.0001 for pargyline) were observed. It was noted that deprenyl causes a significant increase in CAT activity (P<0.05) but a significant decrease in SOD activity (P<0.05) in young rats, while it causes only a significant increase in SOD activity in aging rats (P<0.05). Both deprenyl and pargyline cause a significant decrease in conjugated diene levels of aging rats (P<0.05). These results confirm the role of catecholamine oxidation and MAO activity as one of the causative factors in increased oxidant stress during aging. By reducing the oxidant stress observed in aging brain, MAO inhibitors, especially deprenyl, may contribute to the control of the aging process.

Oxidative Stress Markers in Young Patients with Polycystic Ovary Syndrome, The Relationship between Insulin Resistances

OBJECTIVEnPolycystic ovary syndrome is a syndrome of ovarian dysfunction. Oxidative stress, inflammation and endothelial cell activation are thought to play concomitant roles in the pathogenesis of the above diseases particularly in the development of atherosclerotic lesions.nnnRESEARCH DESIGN AND METHODSnWe studied 58 polycystic ovary syndrome patients and age-matched 25 healthy controls consisting of women that have regular, ovulatory cycles and normal androgen levels. Homeostasis Model Assessment-Insulin Resistance for this study was taken as 1.75 that is the upper level of confidence interval of %95 of the mean of the healthy group. PCOS patients were divided into two groups as for below the cut-off level (<1.75) and above the cut-off level (> or =1.75). hs-CRP, fibrinogen, malondialdehyde, nitric oxide and disulfide level results were compared both in PCOS and control groups.nnnRESULTSnIn this study, sensitive CRP was found to be statical significantly higher in polycystic ovary syndrome groups whose Homeostasis Model Assessment-Insulin Resistance were > or =1.75 and <1.75 when compared to the control group. But, no significantly correlation was determined between malondialdehyde, nitric oxide and disulfide levels and CRP elevation.nnnCONCLUSIONSnIn our study, because those participants were young and non- obese patients with PCOS, malondialdehyde, nitric oxide and disulfide levels and Carotid Artery Intima-Media Thickness measurements as a pre-indicator of cardiovascular disease were not found to be different from those of the controls.

Effect of vitamin E and C supplementation combined with oral antidiabetic therapy on the endothelial dysfunction in the neonatally streptozotocin injected diabetic rat

This study investigates the contribution of vitamin supplementation to the efficacy of oral antidiabetic therapy on the reversal of endothelial dysfunction in a model of type‐2 diabetes in rat.

The relationship of the interleukin-6 -174 G>C gene polymorphism with oxidative stress markers in Turkish polycystic ovary syndrome patients.

Objective: Interleukin-6 (IL-6) is a key pro-inflammatory and immune-modulatory cytokine of relevance for cardiovascular (CD) diseases. Cardiovascular risk factors that have been reported include oxydative stress markers [nitric oxide (NO), malondialdehyde (MDA), disulphite (SH)]. We aimed to evaluate the relation between the IL-6 G/C gene polymorphism and oxidative stress markers in polycystic ovary syndrome (PCOS) patients. Design and patients: We studied 85 PCOS patients and 115 healthy controls. PCOS was defined by the Rotterdam PCOS consensus criteria. Results: The genotype IL-6 distribution did differ between the control group (CC 9.6%, GC 63.4%, GG 27.0%) and the PCOS patients (CC 4.7%, GC 29.4%, GG 65.9%) (p<0.001). The frequency of the polymorphic G allele was also not similar for the group with PCOS as for the control group with 80.6% and 58.7%, respectively (p<0.001). No statistically significant difference was determined for MDA and NO levels in PCOS patients and control group (p>0.05). Only SH levels were found to be high in favor of patient group (p<0.05). No statistically significant difference was determined between IL-6 G/C gene polymorphism and oxidative stress markers in PCOS patients and in the control group. Conclusion: Gene polymorphism of IL-6 −174 G>C is a risk factor for PCOS in Turkish patients. IL-6 gene polymorphisms are not related to NO, MDA, and SH levels in PCOS. Our negative results in risks factors of CV disorders can probably be explained by the fact that metabolic parameters and endothelial systems of patients may not yet be affected in this short period of time.

Effect of I-deprenyl and gliclazide on oxidant stress/antioxidant status and dna damage in a diabetic rat model.

Background: This study investigates the possible effect of monoamine oxidase inhibitor (MAOI), selegyline (l-deprenyl), in combination with oral antidiabetic-gliclazide (OAD), in preventing oxidative stress in streptozotocin-induced diabetes model in male Swiss Albino rats by measuring oxidant stress/DNA damage and antioxidant levels. Methods: Diabetic rats were divided into four groups (n = 10) as [1] diabetic untreated (DM), [2] deprenyl treated (DM + D), [3] gliclazide treated (DM + O), and [4] gliclazide and deprenyl treated (DM + O + D). Controls were divided into two groups (n = 8) [1] untreated (C), and [2] deprenyl treated (C + D). Gliclazide 5 mg/kg and/or MAOI 0.25 mg/kg daily were given orally by gavage for 4 weeks. At the end of the 12th week, catalase and superoxide dismutase (SOD) levels in erythrocyte lysates (EL); total antioxidant status (TAS), 8-hydroxy-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and vitamin A and E levels in plasma, MDA, and MAO in liver homogenates were determined. Results: Diabetic rats showed a decrease in EL-SOD, plasma TAS, and vitamin E, and an increase in plasma 8-OHdG, plasma, and liver MDA levels (p < 0.05). Gliclazide and/or deprenyl decreased 8OHdG levels and increased antioxidant levels and survival when compared with untreated diabetic rats (p < 0.05). The lowest 8-OHdG levels were determined in the DM + O + D group. Conclusions: The combined treatment of deprenyl and gliclazide may contribute to the control of the physiopathological mechanisms underlying both the process of aging and type 2 diabetes by reducing oxidant stress and DNA damage, improving antioxidant status, and increasing survival, and may have implications for further clinical studies.

Thrombin-activatable fibrinolysis inhibitor and cardiovascular risk factors in polycystic ovary syndrome.

OBJECTIVEnWe aimed to assess circulating thrombin activatable fibrinolysis inhibitor (TAFI) levels and carotid intima-media thickness (CIMT) in PCOS patients and control subjects. In this study we aimed to evaluate the relation between the levels of TAFI and homocysteine, high sensitive CRP (hsCRP), fibrinogen and CIMT in PCOS patients carrying a potential risk for developing CVD and diabetes and compared with age- and body mass index-matched controls.nnnRESEARCH DESIGN AND METHODSnWe studied 68 PCOS patients and 26 healthy controls. We conducted an observational study examining noninvasive markers of early CV disease in women with PCOS including structural CIMT. Noninvasive markers of early CVD, CIMT were measured in PCOS patients and control subjects. Metabolic parameters included fasting insulin and glucose levels, lipid and androgen levels, TAFI levels, hsCRP.nnnRESULTSnFasting glucose levels, prolactin, TSH, Total-cholesterol, LDL-cholesterol, triglyceride, estradiol, DHEA-S and age were similar in the two groups, whereas serum insulin, fibrinogen, hs-CRP, 17-OHP, free-testosterone, total testosterone, HOMA-IR, HDL were significantly elevated in PCOS patients in comparison to control subjects (p<0.05). Plasma TAFI levels were similarly in PCOS patients compared with healthy controls. No difference was observed in the combined IMT among the studied groups.nnnCONCLUSIONSnIn our study, no significant difference in lipid parameters was determined between patients with PCOS and healthy controls. In our study, we did not observed any difference in CIMT measurements and TAFI levels between patients with PCOS and healthy controls that can be explained by their low ages and short duration of PCOS.

Age and sex related alterations in serum and platelet monoamine oxidase.

The process of aging presents itself with various alterations in physiological events. Although the turnover of catecholamines increases with aging, there is a lack of response to catecholamines in target tissues. One of the key enzymes in catecholamine metabolism is monoamine oxidase. It has been suggested that tissue and serum monoamine oxidase activities show pathological alterations in various diseases while physiological fluctuations can also be detected in normals. The aim of this study is to determine the sex and age related changes of platelet and serum monoamine oxidase in healthy volunteers. In this study, 75 healthy volunteers of different ages (21-80 a) and sexes (40 females, 35 males) were included. Serum and platelet monoamine oxidase determinations were performed spectrophotofluorometrically by Tufvessons (Scand J Clin Lab Invest 1970; 26:151-4) and Kramls (Biochem Pharmacol 1965; 14:1684-6) modified methods, respectively. While there was no significant difference in serum monoamine oxidase activities related to age and sex, platelet monoamine oxidase manifested a significant increase in females compared to males (p < 0.05) and the mean values in both sexes showed an increase with age (p < 0.001). The results of this study imply that platelet monoamine oxidase shows an age related increase which is more prominent in females.

Effect Of G2706A and G1051A polymorphisms of the ABCA1 gene on the lipid, oxidative stress and homocystein levels in Turkish patients with polycystıc ovary syndrome

BackgroundObesity, insulin resistance and hyperandrogenism, crucial parameters of Polycystic ovary syndrome (PCOS) play significant pathophysiological roles in lipidemic aberrations associated within the syndrome. Parts of the metabolic syndrome (low HDL and insulin resistance) appeared to facilitate the association between PCOS and coronary artery disease, independently of obesity. ABCA1 gene polymorphism may be altered this components in PCOS patients.In this study, we studied 98 PCOS patients and 93 healthy controls. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin, malondialdehyde, nitric oxide, disulfide levels and ABCA genetic study.ResultsIn PCOS group fasting glucose, DHEAS, 17-OHP, free testosterone, total-cholesterol, triglyceride, LDL-cholesterol and fibrinogen were significantly different compare to controls. The genotype ABCA G2706A distribution differed between the control group (GG 60.7%, GA 32.1%, AA 7.1%) and the PCOS patients (GG 8.7%, GA 8.7%, AA 76.8%). The frequency of the A allele (ABCAG2706A) was higher in PCOS patients than control group with 13,0% and 23,2%, respectively. In this study, the homocystein and insulin levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.ConclusionsWe found higher percentage of AA genotype and A allele of ABCA G2706A in PCOS patients compare to controls. The fasting insulin and homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.