Inducing Effect of Corylus avellana on Cytotoxic Activity in Lung and Breast Cancer Cells via Apoptosis.

Turkish hazelnut (Corylus avellana L. cv Tombul) is a widely used nut in the chocolate industry and is also rich in polyphenol content, which promises anticancer effects. The anti-cancer and apoptotic effects of hazelnut leaves extracts examined on lung and breast cancer cells. Sulforhodamine B (SRB) and Adenosine 5'- triphosphate (ATP) assays were carried out for cell viability measurement. The mode of cell death was shown morphologically by the double fluorescence staining. Apoptosis was determined by performing caspase-mediated cytokeratin 18 (M30 ELISA) and western blot analysis. PARP, caspase 3, caspase 8, DR4, and GAPHD (Glyceraldehyde-3-phosphate Dehydrogenase) protein bands were visualized as markers of apoptosis. A wound healing test was employed to measure cell migration. Methanol extract of hazelnut leaf exhibited inhibition of cell growth activities in a dose-dependent manner. IC50 values were determined as 32.17 µg/ml in MCF-7, 32.16 µg/ml in MDA-MB-231, 20.40 µg/ml in A549 and 12.04 µg/ml in H1299 cells for ethanol extract while it was determined as 21.08 µg/ml in MCF-7, 40.16 µg/ml in MDA-MB-231, 22.04 µg/ml in A549 and 5.91 µg/ml in H1299 cells in methanol extract. In comparison, methanol leaf extracts were more effective in H1299 cells (IC50 value was 5.91 µg/ml).In comparison, ethanol leaf extracts were more effective in H1299 cells (IC50 value was 9.722 µg/ml). Western blot analysis demonstrated that hazelnut leaf extract treatment of cancer cells led to cell death via apoptosis and inhibited cell migration in lung and breast cancer cell lines. The cytotoxic effects of hazelnut extract on breast and lung cancer cells might be valuable and promising in elucidating cell death mechanisms for the development of new methods in cancer treatment.

Toxic metal and trace element status in the breast milk of Turkish new-born mothers.

BACKGROUND AND AIM: This study aims to evaluate the toxic metal and trace element concentrations in breast milk obtained from new-born nursing mothers in rural Giresun province, located on the coast of the Black Sea. METHODS: Milk samples were randomly collected once from early lactation of 50 nursing mothers. Inductively coupled plasma mass spectrometry was used to analyse the concentrations of iron (Fe), nickel (Ni), manganese (Mn), cobalt (Co), chromium (Cr), copper (Cu), zinc (Zn), arsenic (As), molybdenum (Mo), cadmium (Cd) and lead (Pb) in the breast milk. Shapiro-Wilk test was used to evaluate the distribution of data. The Pearson-J correlation was used for normally distributed elements, and Spearman correlation analysis was used for others. RESULTS: The mean amounts of elements were 3.36 µg kg-1 of Cr, 9.26 µg kg-1 of Mn, 797 µg kg-1 of Fe, 1.99 µg kg-1 of Ni, 5.92 µg kg-1 of Cu, 379 µg kg-1 of Zn and 2.23 µg kg-1 of Pb. Co, As, Mo and Cd concentrations were below the detection limit. A highly significant correlation was found between iron and Nickel in breast milk. CONCLUSION: Our findings were evaluated in comparison with the WHO data, and whether they were in accordance with the recommended Dietary Reference Intake (DRI) values for 0-6-months-old infants was calculated. Pb levels were similar to those of WHO, while As and Cd were below the measurable limit. Fe, Mn, and Cr concentrations were higher than WHO data, while Co, Ni, Cu and Zn were lower. This research is the first study conducted in this region.

Association of increased levels of omentin-1 and carotid intima-media thickness with early signs of cardiovascular risk in patients with polycystic ovary syndrome: A prospective case control study.

AIM: Omentin-1, an adipokine primarily secreted from visceral adipose tissue, regulates metabolic homeostasis, whereas carotid intima-media thickness (CIMT) is a valid marker for early diagnosis of atherosclerosis. We aimed to investigate whether polycystic ovary syndrome (PCOS) is related to levels of omentin-1 and CIMT and demonstrate the association with cardiovascular risk. METHODS: A prospective case-control study was performed on 47 PCOS patients and 35 healthy subjects. Hormonal and metabolic parameters, levels of serum omentin-1, and CIMT were evaluated in the two groups. RESULTS: The right, left, total CIMT, and levels of serum omentin-1 were significantly higher in the PCOS group than in the healthy controls (p = 0.015, p = 0.009, p = 0.021, and p = 0.002, respectively). Using multiple linear and backward elimination regression analyses, serum omentin-1 was found to be independently associated with age and Ln-transformed homeostasis model assessment of insulin resistance, and cardiovascular parameters were independently associated with body mass index (BMI). In the PCOS group, the means of right, left, and total CIMT were significantly higher in the subgroup with BMI levels ≥25 kg/m2 compared to the subgroup with BMI levels <25 kg/m2 (p < 0.001 for all comparisons). CONCLUSION: A significant increase in CIMT is associated with cardiovascular risk in patients with PCOS. Levels of serum omentin-1 were found to be significantly higher in early PCOS cases at a younger age, acting as a protective acute-phase reactant.

Investigating Fetuin-A and Paraoxonase-1 Activity as Markers in Polycystic Ovary Syndrome Based on Body Mass Index: A Prospective Case-Control Study.

Introduction Polycystic ovary syndrome (PCOS) may have an increased risk for the development of systemic and metabolic pathogenesis such as cardiovascular diseases, insulin resistance (IR), diabetes mellitus (DM) and dyslipidemia. However, there is no reliable marker to show the relation. Fetuin-A is an adipokine whereas paraoxonase-1 (PON-1) is a high-density lipoprotein-linked enzyme to demonstrate oxidative stress. This study aimed to evaluate serum fetuin-A and PON-1 levels in infertile PCOS women based on body mass index (BMI). Methods A prospective case-control study in a university setting was designed. A total of 88 patients admitted to the Giresun University Faculty of Medicine Gynecology Clinic between February and April 2021 were included in the study. The subjects were divided as follows: PCOS-low-BMI (BMI≤25) vs. Controls-low-BMI (BMI≤25) and PCOS-high-BMI (BMI>25) vs. Controls-high-BMI (BMI>25). Those who had at least two criteria of the 2003 Rotterdam Consensus were diagnosed with PCOS. Serum fetuin-A and PON-1 levels were compared. Results The mean levels of fetuin-A were not significantly different in the groups (p=0.955). Serum PON-1 levels were lower in the PCOS group (109.1±61.4 vs. 140.1±80.0; p=0.040), but it lost significance with adjusted values for covariants as age and BMI. Although PON-1 was not significantly different in the PCOS group of BMI<25 kg/m2 subgroup, it was significantly lower in the PCOS group of BMI≥25 kg/m2 subgroup (p=0.820 vs. p=0.048). Conclusion Serum fetuin-A activity did not differ with PCOS. Serum PON-1 might be a promising and research-worthy marker, especially for obese PCOS patients.

Cytotoxic and genotoxic effects of an endemic plant of Turkey Salvia kronenburgii on breast cancer cell lines.

CONTEXT: The natural products derived from plants are the important sources that can be used for breast cancer treatment. Salvia species and their derived products were recommended as potential antitumor substances. AIM: The potential cytotoxic and genotoxic effects of Salvia kronenburgii have been investigated on breast cancer cell lines, MCF-7 and MDA-MB-231. MATERIALS AND METHODS: Determination of chemical compounds of S. kronenburgii was done using a gas chromatography coupled to time-of-flight mass spectrometry system and a dual-stage commercial thermal desorption injector. Growth inhibition of the S. kronenburgii was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and ATP viability assays. The cell death mode was detected by fluorescent dyes. Genotoxic effect of S. kronenburgii was measured by comet assay. RESULTS: S. kronenburgii showed antiproliferative effect in a dose-dependent manner on MCF-7 and MDA-MB-231 cell lines by inducing apoptosis-like cell death. The pyknotic cell nuclei were observed at the cell lines in response to S. kronenburgii. Furthermore, significant increase was shown in genetic damage index and frequencies in the damaged cells. CONCLUSION: S. kronenburgii might be a promising natural source for cancer therapy. Further experiments need to be done in vivo to understand of the anticancer effects of this plant.

Cancer Statistics in Giresun Province, Turkey: A 12-Years Retrospective Review.

AIM: The aim of this retrospective study was to analyze 6,613 diagnosed cancer cases in the Black Sea Turkish province of Giresun over a period of 12 years. MATERIAL AND METHOD: Data of this retrospective crosssectional study was collected from 6,613 cancer patients at Prof. Dr. A. Ilhan Özdemir Education and Research Hospital between 2005- 2016. MINITAB 15 package software was used for statistical analysis. Chi-Square test and differences between two ratios significance test were used to calculate the relationship between two nominal (categorical) variables. RESULTS: Total 6,613 cancer patient's (3,759 men, 56.8% and 2,854 women, 43.2%) average age is 66.27±17.17. The most frequent types of cancer found among men included prostate (24.4%), bronchus-lung (12.5%) and colorectal (11.15%) cancer; whilst among for women it was breast (26%), thyroid (14.9%) and skin (10.6%) cancer, respectively. Kidney, bronchus-lung, skin, larynx, breast, bladder and thyroid cancer types were determined to be statistically significant according to gender (p<0.05). CONCLUSION: We reviewed the diagnosed cancer cases in Giresun province from 2005 to 2016. For men, the order of the most frequent cancer types mentioned is consistent with the statistics of both the European Union (EU) as well as the United States of America (USA); whereas for women it was consistent with Turkey's own national statistics. However, our findings state that thyroid cancer is the second most common cancer type among Turkish women, this is in contrast to most other parts of the world, the EU and USA.

Neuroprotective effects of erythropoietin against oxidant injury following brain irradiation: an experimental study.

INTRODUCTION: Radiation therapy (RT) is a major treatment modality, and the central nervous system is a dose-limiting organ in clinical RT. This experimental study aims to present the evaluation of the neuroprotective effects of erythropoietin (EPO) against oxidant injury following brain irradiation in rats. MATERIAL AND METHODS: Forty Wistar rats were randomly assigned to four groups (n = 10 each). In group 1 the rats received no EPO and underwent sham RT. The rats in groups 2 and 3 received EPO. In group 2 rats underwent sham RT, while in group 3 rats received RT. The rats in group 4 received no EPO and underwent RT. Rats were irradiated using a Cobalt-60 teletherapy machine using a single fraction of 20 Gy covering the whole brain. Cervical dislocation euthanasia was performed. The nitrite and malondialdehyde (MDA) levels and the superoxide dismutase (SOD) and glutathione peroxidase (GSHPX) activities were evaluated in dissected brain tissues. RESULTS: The nitrite and MDA levels were higher in the RT group (2.10 ±0.62 ppm, 26.02 ±2.16 nmol/ml; p < 0.05) and lower in the EPO + RT group (1.45 ±0.12 ppm, 25.49 ±1.90 nmol/ml; p < 0.05). The SOD and GSHPX activity was higher in the EPO + RT group (2.62 ±0.49 U/mg, 1.75 ±0.25 U/mg, p < 0.05). CONCLUSIONS: This study supports the probable neuroprotective effects of EPO against oxidant injury following brain irradiation in a rat model, presumably through decreasing free radical production and increasing expression of antioxidant enzymes.

Correlations between oxidative DNA damage, oxidative stress and coenzyme Q10 in patients with coronary artery disease.

The correlation of coronary artery disease (CAD) with pro-oxidant/antioxidant balance and oxidative DNA damage was investigated. Seventy-seven patients with CAD and 44 healthy individuals as control were included in this study. The comparative ratios of ubiquinol-10/ubiquinone-10, 8-hydroxy-2(')-deoxyguanosine/deoxyguanosine and the level of MDA measured by HPLC and the activities of GPX and SOD by colorimetric approach in blood samples obtained from patients with CAD were unraveled.8-OHdG/dG ratios, serum MDA level and GPX activity were found significantly elevated level in serum of CAD patients compared to control group. The SOD activity was observed in stable levels in CAD patients. Ubiquinol-10/ubiquinone-10 ratio was significantly lower in patients with CAD than the controls. The positive correlation was observed between 8-OHdG/dG ratios in both MDA levels and GPX activity, while the significant negative correlation was seemed between the ratio of 8-OHdG/dG and ubiquinol-10/ubiquinone-10 as well as MDA levels and ubiquinol-10/ubiquinone-10 ratio. We conclude that, both the disruption of pro-oxidant/antioxidant balance and oxidative stress in DNA may play an important role in the pathogenesis of coronary artery disease.

Accelerated atherosclerosis in haemodialysis patients; correlation of endothelial function with oxidative DNA damage.

BACKGROUND: Accelerated atherosclerosis is the major cause of mortality in patients on chronic haemodialysis (HD). The aim of this study was to evaluate the relationship between oxidative DNA damage [8-hydroxy-2'-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG ratio)], oxidative stress biomarkers and endothelial function in HD patients as an indicator of atherosclerosis. METHODS: Forty-four chronic HD patients without known atherosclerotic disease and 55 age- and sex-matched healthy individuals were included in the study. Plasma malondialdehyde (MDA) levels and 8-OHdG/dG ratio were determined as oxidative stress markers. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured as antioxidants. Endothelial function was assessed by ultrasonography. RESULTS: 8-OHdG/dG ratio and MDA levels were higher in HD patients than controls while SOD and GPx activities were lower in HD patients compared to controls. Flow-mediated dilatation FMD% in HD patients were lower than the control group (7.28 ± 0.79 versus 11.18 ± 0.82, P < 0.001). There was a significant negative correlation between FMD% and 8-OHdG/dG ratio (r = -0.678, P < 0.01) and MDA levels (r = -0.517, P < 0.01), while there was a significant positive correlation between FMD% and SOD (r = 0.538, P < 0.01) and GPx levels (r = 0.720, P < 0.01). CONCLUSIONS: Our data have demonstrated that HD patients exhibit increased oxidative DNA damage and decreased antioxidant activity. We propose that endothelial function is negatively correlated with 8-OHdG/dG ratio and positively correlated with antioxidant enzymes. To our knowledge, this is the first study to demonstrate the inverse relationship between endothelial function and plasma oxidative DNA damage in HD patients.

Lipid peroxidation, DNA damage and coenzyme Q10 in lung cancer patients--markers for risk assessment?

OBJECTIVES: Early diagnosis and prevention is very important for lung cancer patients. Previous studies have emphasized that the level of coenzyme Q10 (CoQ10), present primarily in mitochondria, decreases with age and is low in patients with chronic diseases. Our goal was to find out if there is any relationship between lung cancer and CoQ10 and lipid peroxidation levels. DESIGN AND METHODS: Blood samples from lung cancer patients were collected. Total and oxide CoQ10 levels, 8-OHdG (product of DNA damage), and malondialdehyde (MDA) levels (lipid peroxidation) were analyzed with high performance liquid chromatography (HPLC). RESULTS: The MDA level (P<0.001) and DNA damage rate (8-OHdG) (P<0.001) was higher in cancer patients than in the control group; in contrast, theCoQ10 enzyme level was significantly lower (P<0.001). CONCLUSION: The results suggest that the aforementioned parameters can be useful for lung cancer risk assessment.

Oxidative DNA damage correlates with carotid artery atherosclerosis in hemodialysis patients.

Oxidative stress is accepted as a nonclassical cardiovascular risk factor in chronic renal failure patients. The aim of this study was to evaluate the relation between oxidative DNA damage (8-hydroxy-2'-deoxyguanosine/deoxyguanosine [8-OHdG/dG] ratio), oxidative stress biomarkers, antioxidant enzymes, and carotid artery intima-media thickness (CIMT) in hemodialysis (HD) patients. Forty chronic HD patients without known atherosclerotic disease and 48 age- and sex-matched healthy individuals were included in the study. Plasma malondialdehyde (MDA) levels and 8-OHdG/dG ratio were determined as oxidative stress markers. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured as antioxidants. CIMT was assessed by carotid artery ultrasonography. 8-OHdG/dG ratios and MDA levels were higher; SOD and GPx activities were lower in HD patients compared to controls. HD patients had significantly higher CIMT compared to controls (0.61 ± 0.08 vs. 0.42 ± 0.05, p < 0.001). There was a significant positive correlation between CIMT and 8-OHdG/dG ratio (r = 0.57, p < 0.01) and MDA levels (r = 0.41, p < 0.01), while there was a significant negative correlation between CIMT and SOD (r = -0.47, p < 0.01) and GPx levels (r = -0.62, p < 0.01). It is firstly demonstrated that CIMT is positively correlated with oxidative DNA damage in HD patients without known atherosclerotic disease.

Trace elements, heavy metals and vitamin levels in patients with coronary artery disease.

AIM: In the present study, we aimed to assess serum concentrations of zinc (Zn), copper (Cu), iron (Fe), cadmium (Cd), lead (Pb), manganese (Mn), vitamins A (retinol), D (cholecalciferol) and E (α-tocopherol) in patients with coronary artery disease (CAD) and to compare with healthy controls. METHODS: A total of 30 CAD patients and 20 healthy subjects were included in this study. Atomic absorption spectrophotometry (UNICAM-929) was used to measure heavy metal and trace element concentrations. Serum α-tocopherol, retinol and cholecalciferol were measured simultaneously by high performance liquid chromatography (HPLC). RESULTS: Demographic and baseline clinical characteristics were not statistically different between the groups. Serum concentrations of retinol (0.3521 ± 0.1319 vs. 0.4313 ± 0.0465 mmol/I, p=0.013), tocopherol (3.8630 ± 1.3117 vs. 6.9124 ± 1.0577 mmol/I, p<0.001), cholecalciferol (0.0209 ± 0.0089 vs. 0.0304±0.0059 mmol/I, p<0.001) and Fe (0.5664 ± 0.2360 vs. 1.0689 ± 0,4452 µg/dI, p<0.001) were significantly lower in CAD patients. In addition, while not statistically significant serum Cu (1.0164 ± 0.2672 vs. 1.1934 ± 0.4164 µg/dI, p=0.073) concentrations were tended to be lower in patients with CAD, whereas serum lead (0.1449 ± 0.0886 vs. 0.1019 ± 0.0644 µg/dI, p=0.069) concentrations tended to be higher. CONCLUSIONS: Serum level of trace elements and vitamins may be changed in patients with CAD. In this relatively small study we found that serum levels of retinol, tocopherol, cholecalciferol, iron and copper may be lower whereas serum lead concentrations may be increased in patients with CAD.

Catalase, carbonic anhydrase and other biochemical parameters in esophageal cancers in Turkey.

PURPOSE: The main aim of our investigation is to show possible changes in antioxidant balance and selected biochemical parameters in esophageal cancers. MATERIALS AND METHODS: This study was performed for the determination of levels in 25 patients diagnosed as having cancer in the Yuzuncu Yil University (Medical Oncology) and 15 healthy volunteers at same department with negative cancer signs. RESULTS: The activity levels of catalase of sick and health groups were 33.8±4.31 (EU/gHg)-1, 122.4±31.7 (EU/gHg)-1, respectively. Th differance between the average levels was significant (p<0.001). CA (carbonic anhydrase) activity was 2.19±0.12 (EU/gHg)-1, 2.46±0.32 (EU/gHg)-1 in groups at same order with no statistical significance (p>0.05). The levels of albumin, globulin, ferritin, ALT, LDH, glucose, CRP, AST and uric acid were also determined in sick and healthy groups: 4.04±0.24, 4.04±0.43 gr/dl (p>0.05); 4.46±0.82, 3.17±0.10g/dl (p>0.05); 175.4±29.1, 260.4±15.45g/dI (p<0.001); 12.7±1.13, 19.5±1.91 ng/ml (p<0.001); 317.6±13.8, 298.0±12.1 mg/dl (p>0.05); 106.5±12.1, 89.7±2.2 (p>0.05), 5.94±1.04, 4.41±0.28 U/L (p>0.05); 19.4±1.68, 19.5±1.91 mg/dl (p>0.05); 30.0±3.24, 10.5±0.64 mg/dl (p<0.01) respectively. CONCLUSIONS: Consequently, in diagnosis of esophageal cancer, CA, CRP, uric acid and antioxidant examinations may be very important factors. Additional studies are needed to further address this important issue.

Relationship between erythrocyte catalase and serum adenosine deaminase activities in eclampsia.

OBJECTIVE: To examine the relationship between antioxidant status and T-cell activation in the pathogenesis of eclampsia by measuring the activities of erythrocyte catalase, an enzyme of antioxidant mechanism, and serum adenosine deaminase (ADA), regarded as a marker of T-cell activation. METHODS: A total of 60 patients [20 eclamptic (E) pregnant women, 20 healthy pregnant (HP) women and 20 non-pregnant (NP) women] were included in the study. Maternal venous blood samples were obtained from each patient during weeks 28-37 of gestation, and biochemical analyses of catalase activity in erythrocytes and ADA activity in serum were carried out. RESULTS: Erythrocyte catalase activity was significantly lower and serum ADA activity was significantly higher in the E pregnant women when compared with the HP women and NP women (P <0.001). No significant correlation was observed between erythrocyte catalase activity and serum ADA activity. CONCLUSIONS: Erythrocyte catalase and serum ADA activities may at least in part contribute to the pathogenesis of eclampsia. However, more studies are needed to verify and clarify the relationship between antioxidant status and T-cell activation in eclampsia.