Effect of atorvastatin therapy on oxidant-antioxidant status and atherosclerotic plaque formation

PubMed ID: 21731885Background: The aim of this study was to determine the oxidant-antioxidant status and lipid peroxidation products, as well as paraoxonase and atherosclerotic plaque formation, in a hypercholesterolemic atherosclerosis rabbit model to investigate the effects of atorvastatin in the atherosclerotic process. Methods: Forty male New Zealand rabbits were divided into four groups, ie, a control group receiving standard pellets, a group receiving atorvastatin therapy, a hypercholesterolemic group receiving an atherogenic diet, and a group receiving both an atherogenic diet and atorvastatin. Results: The atherogenic diet increased the levels of low-density lipoprotein (LDL) thiobarbituric acid reactive substances (1.84 vs 3.79 nmol/mg protein) and LDL-conjugated diene (147 vs 318 µmol/mg protein) after induction of oxidation by Cu2+, despite an increase of superoxide dismutase activity. Treatment with atorvastatin limited LDL oxidation significantly (LDL thiobarbituric acid reactive substances 2.19 nmol/mg protein, LDL-conjugated diene 222 µmol/mg protein). Paraoxonase, which prevents LDL oxidation and inactivates LDL-derived oxidized phospholipids, showed a pronounced decrease in the group receiving the atherogenic diet (110 U/L to 28 U/L), and atorvastatin treatment increased paraoxonase activity. Histological examination of arcus aorta tissues from the hypercholesterolemic group showed abundant plaque formation surrounding and obstructing the lumen, whereas treatment with atorvastatin prevented or limited plaque formation, keeping the plaque thin and localized. Conclusion: Atorvastatin has dramatic antiatherosclerotic effects, part of which seems to be due to the antioxidant features of the parent drug and/or its metabolites, favoring inhibition of LDL oxidation. © 2011 Sezer et al, publisher and licensee Dove Medical Press Ltd

Fenofibrate Treatment Enhances Antioxidant Status and Attenuates Endothelial Dysfunction in Streptozotocin-Induced Diabetic Rats

Diabetic endothelial dysfunction is accompanied by increased oxidative stress and upregulated proinflammatory and inflammatory mediators in the vasculature. Activation of peroxisome proliferator-activated receptor-alpha (PPAR-α) results in antioxidant and anti-inflammatory effects. This study was designed to investigate the effect of fenofibrate, a PPAR-α activator, on the endothelial dysfunction, oxidative stress, and inflammation in streptozotocin diabetic rats. Diabetic rats received fenofibrate (150 mg kg−1 day−1) for 4 weeks. Fenofibrate treatment restored the impaired endothelium-dependent relaxation and increased basal nitric oxide availability in diabetic aorta, enhanced erythrocyte/liver superoxide dismutase and catalase levels, ameliorated the abnormal serum/aortic thiobarbituric acid reactive substances, and prevented the increased aortic myeloperoxidase without a significant change in serum total cholesterol and triglyceride levels. It did not affect the decreased total homocysteine level and the increased tumor necrosis factor-α level in the serum of diabetic rats. Fenofibrate-induced prevention of the endothelial function seems to be related to its potential antioxidant and antiinflammatory activity

Infertility and the Presence of Insulin Resistance Are Associated With Increased Oxidative Stress in Young, Non-obese Turkish Women With Polycystic Ovary Syndrome

WOS: 000353251000010PubMed ID: 25850594Study Objective: To investigate the relationship between both insulin resistance and fertility and the oxidant/antioxidant system in young, non-obese patients diagnosed with polycystic ovary syndrome (PCOS). Design: Case-control study. Setting: Department of Obstetrics and Gynecology, Ege University, Izmir, Turkey. Participants: PCOS patients without insulin resistance (IR-) (n = 33), PCOS patients with insulin resistance (IR+) (n = 27), and healthy controls (n = 30). Patients with PCOS and regular sexual intercourse were further divided into infertile (n = 14) and fertile (n = 15) groups. Main Outcome Measures: The malondialdehyde (MDA) and thiol levels as well as the catalase (CAT) and superoxide dismutase (SOD) enzyme activities. Results: Both IR+ and IR- PCOS patients had higher MDA levels and lower thiol levels when compared to the controls (each P < .001). However, only IR- patients had significantly higher SOD (3700.81 +/- 410.13 vs 2614.19 +/- 611.80 U/g Hb; P < .001) and CAT (7565.06 +/- 628.27 vs 6819.61 +/- 539.2 U/g Hb; P < .001) activities when compared to the controls. Infertile PCOS patients had significantly higher MDA levels (347.5 +/- 22.8 vs 278.6 +/- 42.6 nmol/g Hb, P < .001) and lower thiol levels (498.5 +/- 56.2 vs 568.5 +/- 38.6 mu mol/l, P = .001) when compared to fertile patients. Conclusions: The results of this study demonstrated an imbalance in the oxidative-antioxidative system of PCOS patients. This imbalance was worse in IR+ and infertile PCOS patients

LC-MS/MS measurement of leukocyte cystine; effect of preanalytic factors

Sezer, Ebru/0000-0002-6900-3539;WOS: 000509632900074PubMed: 31892015Cystinosis is an autosomal recessive disorder characterized by the accumulation of cystine in lysosomes, causing irreversible damage to organs, especially the kidneys. Intracellular leukocyte cystine concentrations are used to diagnose cystinosis and to monitor cysteamine treatment. the aim of this study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method without derivatization capable of measuring leukocyte intracellular cystine concentrations. During development, the effects of using three different protein precipitation agents were evaluated in terms of sensitivity and the matrix effect, with 12% trichloroacetic acid providing the highest sensitivity. the effects of different blood collection tubes were also assessed in terms of recovery, matrix effect, and protein content. Compared to other methods, our method was quicker (run time of 3 min), was linear over the range 0.078-100 mu M, and had lower limits of detection (0.0192 mu M) and quantification (0.0582 mu M). the intra-day and inter-day reproducibility %CVs were <= 10%. and the method had excellent recovery rates (94%-106%). Other parameters including matrix selectivity, injection carryover, leukocyte lysate stability were also validated and met the acceptance criterias of European Medicines Agency (EMA) Guideline. the assay was successfully applied to quantify cystine leukocyte concentration in healthy and cystinosis patients.Ege University Research FundEge University [16 TIP 002]This project was funded by the Ege University Research Fund (Project Number 16 TIP 002)

How Preeclampsia Affects Oxidant Status and Antiiflammatory Potential of Breast Milk?

WOS: 00044435580011

Assessing Anticancer Potential of Blueberry Flavonoids, Quercetin, Kaempferol, and Gentisic Acid, Through Oxidative Stress and Apoptosis Parameters on HCT-116 Cells

###EgeUn###In recent years, natural products gained popularity with their anti-inflammatory and antioxidant effects mediated by chemical compounds within their composition. Study results offering them as palliative therapy options in cancer or as anticancer agents with high levels of cytotoxicity brought a new approach to combine cancer treatment protocols with these products. From a different perspective, edible types of these products are suggested in daily diets due to their potential cancer preventive effects. Our preliminary work was on blueberry extracts (Vaccinium myrtillus) as a main representative of these natural products, and the contents of the extracts were analyzed with liquid chromatography tandem mass spectrometry (LC MS/MS) to reveal the composition and distribution of polyphenolic compounds within. The most abundant polyphenols detected in V. myrtillus extracts were quercetin, kaempferol, and a phenolic acid, gentisic acid (GA). The compounds were further evaluated on treated HCT-116 cells for their potential anticancer effects by measuring total antioxidant status, total oxidant status, and 8-hydroxydeoxyguanosine levels for evaluation of oxidative stress and through protein array analysis and flow cytometric analysis for evaluation of apoptosis. In analysis of oxidative stress parameters, reduced total oxidant levels and reduced oxidative stress index levels were found in cells treated with the compounds in comparison with untreated cells. In apoptosis-related protein profiles, at least twofold reduction in various apoptotic proteins was observed after quercetin and kaempferol treatment, whereas a different profile was observed for GA. Overall, results of this study showed that quercetin and kaempferol have strong cytotoxic, antioxidant, and apoptotic effects, although GA is mostly effective as an antioxidant polyphenol on HCT-116 cells

Research training program in a Turkish medical school: challenges, barriers and opportunities from the perspectives of the students and faculty members

WOS:000606856200001PubMed: 33397360Background Providing medical students with opportunities for research experience is challenging for medical schools in developing countries. The Research Training Program (RTP), which is carried out in Ege University Faculty of Medicine (EUFM) parallel to the core curriculum, aims to improve the scientific competencies of the highly motivated students and to provide them with the opportunity to conduct a research. The purpose of this project is to evaluate RTP through the perspectives of students and faculty members. Methods This phenomenological study included two groups; students of RTP and faculty members who contributed to the program. Interviews were conducted with the research group whose selection was determined by maximum variation technique. Interviews with new individuals continued until data saturation was reached. Interpretative data analysis started with close reading of the transcripts and generating a list of codes. Coding by two independently, developing categories and themes were the following steps. Results Twenty-one RTP students and 14 faculty members were interviewed. The main motivation for students to participate was the desire to learn how to do research. The introduction course providing the students with the basic competencies needs to be improved in terms of practical activities. It was reported that during the project process students needed intensive guidance especially in finding a research topic and a mentor. The students' lack of time, deficit of enough mentoring and the fact that conducting a research does not provide a competitive advantage for residency are important obstacles to the completion of the program. The most frequently mentioned achievement of the students is to learn all the stages of the research as well as getting acquainted with critical thinking. Conclusions This research showed that it was realistic to implement research programs for highly motivated students in medical schools with conditions like those in EUFM. The solution of mentor shortage emerged in this study is dependent on the adoption of student research as a national policy. Getting acquainted with the interrogative thinking style, conducting research, and making lifelong learning a core value are more important outcomes of research programs than the number of completed projects.Ege University Scientific Research Projects CommissionEge University [18-TIP-018]This research received a funding grant from Ege University Scientific Research Projects Commission (Project No. 18-TIP-018). The funding was used for the purpose of purchasing audio record devices and covering expenses for hiring a professional transcriber