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.

An Experimental Comparison of the Analgesic and Anti-Inflammatory Effects of Safflower Oil, Benzydamine HCl, and Naproxen Sodium

Ali Alaiye,Ercan Kaya,Mehmet Ozgur Pınarbaslı,Nusin Harmancı,Cafer Yıldırım,Dilek Burukoglu Donmez,Cemal Cingi 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.8

The study aims to establish how feasible a natural therapy option (safflower oil) is in the treatment of postoperative pain. Naproxen sodium has already been experimentally proven to be effective for this purpose. Accordingly, the analgesic and anti-inflammatory effects of safflower oil were compared with those obtained with benzydamine HCl and naproxen sodium. Forty-two, healthy, adult female rats of Wistar albino species were divided at random into six groups of seven rats. The intervention allocation was as follows: Group No. 1—physiological saline 0.9%; Group No. 2—safflower oil 100 mg/kg; Group No. 3—safflower oil 300 mg/kg; Group No. 4—benzydamine HCl 30 mg/kg; Group No. 5—benzydamine HCl 100 mg/kg; and Group No. 6—naproxen sodium 10 mg/kg. Following allocation of treatment, pain was induced experimentally and tested in various ways (hot plate test, tail-pinching test, and writhing test) and the efficacy of each treatment in providing peripheral and central analgesia was evaluated. The second stage consisted of providing different treatments to four groups (groups 7–10) of seven rats each, chosen at random. The allocations were as follows: Group No. 7—physiological saline 0.9%; Group No. 8—safflower oil 300 mg/kg; Group No. 9—benzydamine HCl 100 mg/kg; and Group No. 10—naproxen sodium 10 mg/kg. To create experimental inflammation, 2% formaldehyde was injected into the experimental animal's paw and the resulting edema was measured and recorded for a 10-day period. Edema inhibition was calculated as a percentage. The rats were sacrificed and the paw and stomach dissected for histopathological examination. The data were used for statistical analysis, using the Shapiro–Wilk, Kruskal–Wallis H test, and two-way analysis of variance. In the tail-pinching test, it was determined that a 300 mg/kg dose of safflower oil shows central spinal analgesic efficacy and this effect is close in magnitude to 10 mg/kg of the reference material, naproxen sodium. In the squirming test, it was observed that the 100 and 300 mg/kg doses of safflower oil had a peripheral analgesic effect when compared with the serum physiological (placebo) group. The peripheral efficacy of 300 mg/kg safflower oil was found to approximate that of 10 mg/kg naproxen sodium. In rats treated with benzydamine HCl 100 mg/kg, similar peripheral analgesic efficacy to naproxen sodium 10 mg/kg was noted. In the hot plate test, no difference in the analgesic efficacy between the various agents was found. The change in inhibition of edema between the 1st and 10th days was most marked in rats receiving naproxen sodium 10 mg/kg. A significant difference was determined in the safflower oil 300 mg/kg and benzydamine HCl 100 mg/kg groups (P < .001). Regarding histopathology findings in the rat paw, significant differences were seen in venous congestion between placebo and safflower oil 300 mg/kg and in inflammation between the control and benzydamine HCl 100 mg/kg groups. Regarding the histopathology findings in the rat stomach, significant differences were observed in venous congestion between placebo and safflower oil 300 mg/kg; in damage to the epithelium between placebo and safflower oil 300 mg/kg and between naproxen sodium 10 mg/kg and safflower oil; and in cell infiltration and development of edema between placebo and safflower oil 300 mg/kg. It is predicted that further research into safflower oil and benzydamine HCl will create opportunities to develop analgesic–anti-inflammatory therapeutics of a novel kind for the treatment of postoperative pain and inflammation.

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.