Posttreatment Effects of Olea Europaea L. Leaf Extract on Carbon Tetrachloride-Induced Liver Injury and Oxidative Stress in Rats

Derya Ustuner,Emine Colak,Murat Dincer,Neslihan Tekin,Dilek Burukoglu Donmez,Fahrettin Akyuz,Ertugrul Colak,Umut Kerem Kolac,Emre Entok,Mehmet Cengiz Ustuner 한국식품영양과학회 2018 Journal of medicinal food Vol.21 No.9

The aim of this study is to examine the therapeutic effects of Olea europaea L. leaf extract on carbon tetrachloride (CCl4)-induced liver damage in rats. In the experiments, 3- to 4-month-old 28 male Sprague–Dawley rats were divided into four groups: control, O. europaea leaf extract, CCl4, and curative. The CCl4 and curative groups received CCl4 (0.2 mL/kg) intraperitoneally for 10 days to form hepatic injury. O. europaea (80 mg/kg) leaf extract was given orally to the curative group dissolved in distilled water the following 14 days. Hepatic and antioxidant enzyme levels, p53, caspase 3, lipid peroxidation marker malondialdehyde (MDA), and also DNA fragmentation levels were determined to establish oxidative stress in hepatic cell damage and its consequences. After formation of liver damage, oral administration of the O. europaea significantly reduced CCl4-induced elevations of serum alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase levels (P < .001), MDA levels of both blood (P < .001) and liver tissues (P < .001), DNA fragmentation (P < .001), p53 (P < .001), and caspase 3 (P < .001) levels of liver tissues. Also this administration in curative group significantly increased CCl4-induced reductions of superoxide dismutase (SOD) (P < .001) and catalase (CAT) (P < .001) activity of blood samples and decreased SOD (P < .001) and CAT (P < .05) activity observed in liver tissue curative groups compared with CCl4 curative group. In CCl4 group, liver tissue samples exhibited remarkable damage because of CCl4 and reduction of these damages were observed in the curative group. Our results showed that O. europaea leaf extract was effective in reducing hepatic damage caused by CCl4 by reducing lipid peroxidation, regulating antioxidant enzymes, and minimizing DNA damage.

Naringenin Ameliorate Carbon Tetrachloride-Induced Hepatic Damage Through Inhibition of Endoplasmic Reticulum Stress and Autophagy in Rats

Derya Ustuner,Umut Kerem Kolac,Mehmet Cengiz Ustuner,Cihan Tanrikut,Zeynep Ozdemir Koroglu,Dilek Burukoglu Donmez,Hulya Ozen,Hilmi Ozden 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.11

Hepatic fibrosis emerges upon exposure of liver to various chemicals and if not treated, it develops various diseases such as cirrhosis and cancer. Carbon tetrachloride (CCl4) is a widely used toxin in animal models to develop hepatic fibrosis. Accumulation of unfolded proteins in cells causes stress in the endoplasmic reticulum (ER) and various mechanisms are involved in the cell to reduce the damage caused by these unfolding proteins. The most well known of these is the unfolded protein response. Further, autophagy works to remove these proteins if the damage cannot be repaired and is permanent. In our study, we investigated the effects of naringenin (NRG), a flavanon abundant in citrus fruits, on ER stress and autophagy in CCl4-injured rat liver. The animals were given 0.2 mL/kg of CCl4 for 10 days and treatment group was administered 100 mg/kg of NRG for 14 days. Histopathological examination was performed to show liver damage and to determine the therapeutic properties of the active substance. Transmission electron microscopy (TEM) analysis was carried out to establish cell level damage and effect of treatment. In addition, levels of ER stress and autophagy markers of liver were measured. According to our findings, TEM demonstrated positive effect of NRG and histological examinations reported ameliorative effects. In addition, NRG reduced levels of ER stress markers and inhibited autophagy significantly compared to CCl4-treated group. As a result, NRG significantly reduced damage in hepatocytes and provided a significant amelioration.

Effects of a Static Synchronous Series Compensator (SSSC) Based on a Soft Switching 48-Pulse PWM Inverter on the Power Demand from the Grid

Ustun, Taha Selim,Mekhilef, Saad The Korean Institute of Power Electronics 2010 JOURNAL OF POWER ELECTRONICS Vol.10 No.1

In this paper the effects of a Static Synchronous Series Compensator, which is constructed with a 48-pulse inverter, on the power demand from the grid are studied. Extensive simulation studies were carried out in the MATLAB simulation environment to observe the compensation achieved by the SSSC and its effects on the line voltage, line current, phase angle and real/reactive power. The designed device is simulated in a power system which is comprised of a three phase power source, a transmission line, line inductance and load. The system parameters such as line voltage, line current, reactive power Q and real power P transmissions are observed both when the SSSC is connected to and disconnected from the power system. The motivation for modeling a SSSC from a multi-pulse inverter is to enhance the voltage waveform of the device and this is observed in the total harmonic distortion (THD) analysis performed at the end of the paper. According to the results, the power flow and phase angle can be controlled successfully by the new device through voltage injection. Finally a THD analysis is performed to see the harmonics content. The effect on the quality of the line voltage and current is acceptable according to international standards.

Effects of a Static Synchronous Series Compensator (SSSC) Based on a Soft Switching 48-Pulse PWM Inverter on the Power Demand from the Grid

Taha Selim Ustun,Saad Mekhilef 전력전자학회 2010 JOURNAL OF POWER ELECTRONICS Vol.10 No.1

In this paper the effects of a Static Synchronous Series Compensator, which is constructed with a 48-pulse inverter, on the power demand from the grid are studied. Extensive simulation studies were carried out in the MATLAB simulation environment to observe the compensation achieved by the SSSC and its effects on the line voltage, line current, phase angle and real/reactive power. The designed device is simulated in a power system which is comprised of a three phase power source, a transmission line, line inductance and load. The system parameters such as line voltage, line current, reactive power Q and real power P transmissions are observed both when the SSSC is connected to and disconnected from the power system. The motivation for modeling a SSSC from a multi-pulse inverter is to enhance the voltage waveform of the device and this is observed in the total harmonic distortion (THD) analysis performed at the end of the paper. According to the results, the power flow and phase angle can be controlled successfully by the new device through voltage injection. Finally a THD analysis is performed to see the harmonics content. The effect on the quality of the line voltage and current is acceptable according to international standards.

Postmenopausal Osteoporosis Is Associated with Serum Chemerin and Irisin but Not with Apolipoprotein M Levels

( Yaprak Engin-ustun ),( Emel Kıyak Caglayan ),( Ayse Yesim Gocmen2 ),( Muhammed Fevzi Polat ) 대한폐경학회 2016 대한폐경학회지 Vol.22 No.2

Objectives: The objective of this study was to describe the levels of chemerin, irisin and apolipoprotein M (apoM) in women with postmenopausal osteoporosis. Methods: The study included 88 women with postmenopausal osteoporosis. Based on World Health Organization criteria, women with a T-score of ≤ -2.5 were defined as osteoporotic. In this case-control study, postmenopausal women with T-score > -1 were selected as controls (n = 88) and case-matched in a 1:1 ratio based on age (within 2 years) and body mass index (BMI) (within 1.0 kg/m²). ApoM, irisin and chemerin levels were determined by a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results: There were no significant differences in age, BMI, parity, cholesterol and apoM levels between the two groups. C-reactive protein levels were significantly increased in women with osteoporosis. Serum chemerin levels (240.1 ± 46.1 vs. 261.5 ± 50.8 ng/ mL) were significantly lower in the women with osteoporosis, as compared to the controls (P = 0.004). Serum irisin levels were also decreased in women with osteoporosis (0.7 ± 0.2 vs. 0.8 ± 0.2 ng/mL; P = 0.007). Conclusions: In the present study, osteoporosis was associated with decreased levels of circulating chemerin and irisin. These findings suggested that adipokines might play a role in the pathogenesis of osteoporosis. (J Menopausal Med 2016;22:76-79)

Propolis Protects Endotoxin Induced Acute Lung and Liver Inflammation Through Attenuating Inflammatory Responses and Oxidative Stress

Berat Yangi,Mehmet Cengiz Ustuner,Murat Dincer,Cansu Ozbayer,Neslihan Tekin,Derya Ustuner,Emine Colak,Umut Kerem Kolac,Emre Entok 한국식품영양과학회 2018 Journal of medicinal food Vol.21 No.11

Propolis is a natural bee product, and it has many effects, including antioxidant, anti-inflammatory, antihepatotoxic, and anticancer activity. In this study, we aimed to explore the potential in vivo anti-inflammatory, antioxidant, and antiapoptotic properties of propolis extract on lipopolysaccharide (LPS)-induced inflammation in rats. Forty-two, 3- to 4-month-old male Sprague Dawley rats were used in six groups. LPS (1 mg/kg) was administered intraperitoneally to rats in inflammation, inflammation + propolis30, and inflammation+propolis90 groups. Thirty milligram/kilogram and 90 mg/kg of propolis were given orally 24 h after LPS injection. After the determination of the inflammation in lung and liver tissues by 18F-fluoro-deoxy-d-glucose–positron emission tomography (18FDG-PET), samples were collected. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), nitric oxide (NO), and DNA fragmentation were determined. The decrease of MDA levels in inflammation + propolis30 and inflammation + propolis90 groups was determined compared to the inflammation group in lung and liver tissues. The increase of SOD% inhibition in inflammation + propolis90 group was determined in liver, lung, and hemolysate compared to the inflammation group. Increased CAT activities in inflammation + propolis30 and inflammation + propolis90 groups were observed in liver tissue and hemolysate compared to inflammation group. In lung tissue, NO levels were lower in inflammation group compared to the control group, but DNA fragmentation levels were higher. 18F-FDG uptake of tissues in inflammation + propolis30 and inflammation + propolis90 groups was decreased compared to the inflammation group. In conclusion, the data of this study indicate that the propolis application may serve as a potential approach for treating inflammatory diseases through the effect of reducing inflammation and free oxygen radical production.

The Anti-Inflammatory and Antioxidant Effects of Salvia officinalis on Lipopolysaccharide-Induced Inflammation in Rats

Umut Kerem Kolac,Mehmet Cengiz Ustuner,Neslihan Tekin,Derya Ustuner,Emine Colak,Emre Entok 한국식품영양과학회 2017 Journal of medicinal food Vol.20 No.12

Salvia officinalis, which has a high phenolic acid and flavonoid content, is a powerful antioxidant and anti-inflammatory herb. Inflammation plays an important role in the pathophysiology of many diseases and could cause damage by means of oxidative stress. The aim of this study was to investigate the anti-inflammatory and antioxidant activity of S. officinalis formed lipopolysaccharide (LPS)-induced experimental inflammation model. Four- to five-month-old 42 female Wistar albino rats were divided into six groups. Three groups were administered intraperitoneally 1 mg/kg LPS. Twenty-four hours after injection of LPS, 10 and 30 mg/kg S. officinalis extract were given orally to treatment groups. Pulmonary and hepatic 18F-fluoro-deoxy-D-glucose (18F-FDG) uptake was calculated to determine the status of inflammation by 18F-fluoro-deoxy-D-glucose-positron emission tomography (18FDG-PET) scan. Antioxidant enzyme activities and nitric oxide (NO) and malondialdehyde (MDA) levels were determined. Nuclear factor-kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α) levels were also detected in serum. As a result, lung and liver 18F-FDG uptake was found to be higher in the inflammation group than control group. MDA levels in erythrocyte and all tissue samples (liver, lung, and kidney) were found to be significantly higher compared to treatment groups. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities of the inflammation group in the liver, lung, kidney tissues, and erythrocyte SOD and CAT activities were determined to significantly lower than groups treated with S. officinalis. Increased NO, NF-κB, and TNF-α levels were found in the inflammation group. S. officinalis has been observed to have useful effects on LPS-induced inflammation and oxidative stress in rats.

Protective Effects of the Nuclear Factor Kappa B Inhibitor Pyrrolidine Dithiocarbamate on Experimental Testicular Torsion and Detorsion Injury

Kabay, Sahin,Ozden, Hilmi,Guven, Gul,Burukoglu, Dilek,Ustuner, Mehmet Cengiz,Topal, Fatma,Gunes, Hasan Veysi,Ustuner, Derya,Ozbayer, Cansu The Korean Society of Pharmacology 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.4

Testicular torsion results with the damage of the testis and it is a surgical emergency. Pyrrolidine dithiocarbamate (PDTC) is a low-molecular-weight antioxidant and potent inhibitor of nuclear factor kappa B (NF-${\kappa}B$) activation. In this study, we aimed to investigate the effects of PDTC to testicular torsion-detorsion (T/D) injury. Forty adult male Sprague-Dawley rats were separated into four groups. A sham operation was performed in group I. In group II, torsion is performed 2 hours by 720 degree extravaginally testis. In group III, 4 h reperfusion of the testis was performed after 2 h of testicular torsion. In group IV, after performing the same surgical procedures as in group III, PDTC (100 mg/kg, intravenous's) was administered before 30 min of detorsion. The testes tissue malondialdehyde (MDA), superoxide dismutase (SOD) catalase (CAT) level was evaluated. Histological evaluations were performed after hematoxylin and eosin staining. Testicular tissue MDA levels were the highest in the T/D groups compared with treatment group. Administration of PDTC prevented a further increase in MDA levels. Significant decrease occurred in CAT and SOD levels in treatment group compared with the control group. The rats in the treatment group had normal testicular architecture. The results suggest that PDTC can be a potential protective agent for preventing the biochemical and histological changes related to oxidative stress in testicular injury caused by testis torsion.

Protective Effects of the Nuclear Factor Kappa B Inhibitor Pyrrolidine Dithiocarbamate on Experimental Testicular Torsion and Detorsion Injury

Sahin Kabay,Hilmi Ozden,Gul Guven,Dilek Burukoglu,Mehmet Cengiz Ustuner,Fatma Topal,Hasan Veysi Gunes,Derya Ustuner,Cansu Ozbayer 대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.4

Testicular torsion results with the damage of the testis and it is a surgical emergency. Pyrrolidinedithiocarbamate (PDTC) is a low-molecular-weight antioxidant and potent inhibitor of nuclear factorkappa B (NF-κB) activation. In this study, we aimed to investigate the effects of PDTC to testiculartorsion-detorsion (T/D) injury. Forty adult male Sprague-Dawley rats were separated into four groups. A sham operation was performed in group I. In group II, torsion is performed 2 hours by 720 degreeextravaginally testis. In group III, 4 h reperfusion of the testis was performed after 2 h of testiculartorsion. In group IV, after performing the same surgical procedures as in group III, PDTC (100 mg/kg,intravenous’s) was administered before 30 min of detorsion. The testes tissue malondialdehyde (MDA),superoxide dismutase (SOD) catalase (CAT) level was evaluated. Histological evaluations were performedafter hematoxylin and eosin staining. Testicular tissue MDA levels were the highest in theT/D groups compared with treatment group. Administration of PDTC prevented a further increase inMDA levels. Significant decrease occurred in CAT and SOD levels in treatment group compared withthe control group. The rats in the treatment group had normal testicular architecture. The resultssuggest that PDTC can be a potential protective agent for preventing the biochemical and histologicalchanges related to oxidative stress in testicular injury caused by testis torsion.

Effects of Feed Intake and Water Hardness on Fluralaner Pharmacokinetics in Layer Chickens

Ataman Bilge Sari,Yigit Gunes,Ceren Anlas,Fulya Ustun Alkan,Enes Guncum,Oya Ustuner,Tulay Bakirel 대한수의학회 2022 Journal of Veterinary Science Vol.23 No.5

Background: Fluralaner is a novel drug belonging to the isoxazoline class that acts on external parasites of domestic animals. It is used systemically via drinking water, especially against red poultry mite in layer chickens. Fluralaner is frequently used in layers infected with D. gallinae. However, no study to date has investigated the effects of feed intake and water hardness. Objectives: This study aimed to investigate the effects of variable water hardness and feed intake on the pharmacokinetic profile of fluralaner. Methods: Layer chickens were divided into four groups (n = 8): fed + purified water (Group 1), feed restricted + purified water (Group 2), feed restricted + hard water (Group 3), and feed restricted + soft water (Group 4). After administering a single dose of the drug with drinking water, the blood samples were collected for 21 days. Fluralaner concentrations in plasma samples were determined by liquid chromatography/tandem mass spectrometry. The maximum plasma concentration (Cmax), time to reach maximum plasma concentration (tmax), area under the concentration–time curve values (AUC0-21d), half-life (t1/2), and other pharmacokinetic parameters were calculated. Results: Although the highest maximum plasma concentration (Cmax) was determined in Group 1 (fed + purified water), no statistically significant difference was found in the Cmax, tmax, t1/2, MRT0-inf_obs, Vz/Fobs, and Cl/F_obs parameters between the experimental groups. Conclusions: It was concluded that the feed intake or water hardness did not change the pharmacokinetic profile of fluralaner in layer chickens. Therefore, fluralaner could be used before or after feeding with the varying water hardness in poultry industry.