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.

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.

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.

Two alternative models on the relationships between organizational justice, organizational commitment, burnout, and job satisfaction of education supervisors

Mehmet Karakus,Mehmet Ustuner,Mustafa Toprak 한국교육개발원 2014 KEDI Journal of Educational Policy Vol.11 No.1

This study aims to determine the relationships between organizational justice and affective and normative based outcome variables of education supervisors. Two alternative structural equation models were tested. The first model proposed burnout is the outcome of organizational justice and the antecedent of the variables of job satisfaction and organizational commitment. The second model proposed burnout is the outcome of the variables of organizational justice, job satisfaction, and organizational commitment. Although both the models had acceptable fit indices, the comparative fit indices showed the second model was more preferable. In this model, justice perceptions were found to have a positive effect on organizational commitment through the partial mediation effect of job satisfaction, and a negative effect on burnout through the full mediation effect of job satisfaction.

Which Endometrial Pathologies Need Intraoperative Frozen Sections?

Balik, Gulsah,Kagitci, Mehmet,Ustuner, Isik,Akpinar, Funda,Guven, Emine Seda Guvendag Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

Background: Endometrial cancers are the most common gynecologic cancers. Endometrial sampling is a preferred procedure for diagnosis of the endometrial pathology. It is performed routinely in many clinics prior to surgery in order to exclude an endometrial malignancy. We aimed to investigate the accuracy of endometrial sampling in the diagnosis of endometrial pathologies and which findings need intra-operative frozen sections. Materials and Methods: Three hundred nine women applying to a university hospital and undergoing endometrial sampling and hysterectomy between 2010 and 2012 were included to this retrospective study. Data were retrieved from patient files and pathology archives. Results: There was 17 patients with malignancy but endometrial sampling could detect this in only 10 of them. The endometrial sampling sensitivity and specificity of detecting cancer were 58.8% and 100%, with negative and positive predictive values of 97.6%, and 100%, respectively. In 7 patients, the endometrial sampling failed to detect malignancy; 4 of these patients had a preoperative diagnosis of complex atypical endometrial hyperplasia and 2 patients had a post-menopausal endometrial polyps and 1 with simple endometrial hyperplasia. Conclusions: There is an increased risk of malignancy in post-menopausal women especially with endometrial polyps and complex atypia hyperplasia. Endometrial sampling is a good choice for the diagnosis of endometrial pathologies. However, the diagnosis should be confirmed by frozen section in patients with post-menopausal endometrial polyps and complex atypia hyperplasia.

Primary Synovial Sarcoma of Lung

Devrim Cabuk,Berna Ustuner,Asli Gul Akgul,Ozgur Acikgoz,Busra Yaprak,Kazim Uygun,Salih Topcu,Bahar Muezzinoglu 대한흉부외과학회 2014 Journal of Chest Surgery (J Chest Surg) Vol.47 No.3

Synovial sarcoma (SS) is a highly malignant tumor that accounts for 10% of all soft-tissue sarcomas. Primary SS arising from the lung is extremely rare, and the prognosis is poor. We report a case of pulmonary SS presenting with a mass lesion invading the right upper and middle lobes, extending to the mediastinum and the chest wall. After tru-cut biopsy, surgical resection was performed. The final diagnosis was SS (biphasic type) based on histological and immunohistochemical findings. There are no guidelines for optimal treatment due to the rarity of these tumors. Current treatment includes surgery and adjuvant chemotherapy and/or radiotherapy.

MRI Findings of Intrinsic and Extrinsic Duodenal Abnormalities and Variations

Ebru Dusunceli Atman,Ayse Erden,Evren Ustuner,Caglar Uzun,Mehmet Bektas 대한영상의학회 2015 Korean Journal of Radiology Vol.16 No.6

This pictorial review aims to illustrate the magnetic resonance imaging (MRI) findings and presentation patterns of anatomical variations and various benign and malignant pathologies of the duodenum, including sphincter contraction, major papilla variation, prominent papilla, diverticulum, annular pancreas, duplication cysts, choledochocele, duodenal wall thickening secondary to acute pancreatitis, postbulbar stenosis, celiac disease, fistula, choledochoduodenostomy, external compression, polyps, Peutz-Jeghers syndrome, ampullary carcinoma and adenocarcinoma. MRI is a useful imaging tool for demonstrating duodenal pathology and its anatomic relationships with adjacent organs, which is critical for establishing correct diagnosis and planning appropriate treatment, especially for surgery.