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WOS: 000443568400006, PubMed ID: 29973698, Radiotherapy (RT) for prostate cancer (PC) can cause erectile dysfunction (ED) by damaging neurovascular structures with oxidative stress. In this study, we evaluated the effects of resveratrol, an antioxidant, on post-RT ED. Fifty rats in five groups were evaluated; control (C), prostate-confined radiotherapy with short- and long-term vehicle or resveratrol treatment. Cavernosal tissues were obtained to analyze glutathione (GSH), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), 8-hydroxy-2'-deoxy-guanosine (8-OHdG) levels and superoxide dismutase (SOD), caspase-3 activities, sirtuin-1, Foxo-3, nNOS, and eNOS protein expressions. Intracavernosal pressures (ICP) were measured for the long-term treatment group. In the RT long-term vehicle treatment group, tissue GSH, NO, cGMP, and SOD activity were decreased while 8-OHdg levels and caspase-3 activities were increased. Radiotherapy caused a decrease in sirtuin-1, nNOS, and eNOS protein expressions. These parameters were reversed by resveratrol treatment. Foxo-3 protein expressions were unaltered in the RT + short-term vehicle treatment group and started to increase as a defense mechanism in the RT long-term vehicle group; however, resveratrol treatment caused a significant increase in Foxo-3 expressions. Resveratrol preserved the metabolic pathways involved in erectile function and provided functional protection. Resveratrol can be used as a supplementary agent in patients undergoing radiotherapy to preserve erectile function., Marmara University Scientific Research Projects Committee [SAG-B-100914-0311], This study was supported by Marmara University Scientific Research Projects Committee with the grant number SAG-B-100914-0311.

WOS: 000461427300007, Background: Potential targets for prostate cancer therapy are urgently needed for curative of patients. Cyclosporine-A (CsA), an immunosuppressive and a selective cyclooxygenase-2 (COX-2) inhibitor, exerts antitumor activity. However, the molecular effects of CsA is not fully understood in prostate cancer. In this research, we sought to determine role and mechanism of CsA in prostate cancer. Materials and methods: PC3 and DU145 cells were treated with CsA time (12, 24, 48 h) and dose dependent (2.5, 10, 25 mu M) and cell survival, migration, colony formation, expression of apoptosis related proteins/genes using MTT assay, scratch assay, Western blotting/qPCR. At the same time, cells treated with CsA to test on the effects of COX-2 promoter activity using luciferase reporter plasmid. Lastly, functional role in the CsA treatment prostate cancer cells were interrogated for relationship of TGF beta, Akt, caspases and COX-2. Results: These study findings provided direct evidences that the CsA induced apoptosis and downregulated migration. Conclusions: CsA downregulated Akt as well as COX-2 and upregulated TGF beta, resulting in the suppression of cell migration which was augmented a potential therapeutic of CsA in prostate cancer cells., Cumhuriyet University Research Grant [ECZ-003/ECZ-008]; Scientific and Technological Research Council of Turkey (TUBITAK) [214Z057]; Science Academy's Young Scientist Award (BAGEP)-2016, The authors are grateful to Dr. Neerja Kaushik Basu for the kind gift of p-COX-2-Luc reporter plasmids. Authors would like to thank Mustafa Ergul and H. Eren Bostanci from Faculty of Pharmacy in Cumhuriyet University. This work was supported by the Cumhuriyet University Research Grant (Projects ECZ-003/ECZ-008) and by a grant (214Z057) from the Scientific and Technological Research Council of Turkey (TUBITAK) and Science Academy's Young Scientist Award (BAGEP)-2016 to Dr. Ozge Cevik.

WOS: 000381406300002, PubMed ID: 27399230, Although endogenous estrogen is known to offer cardiac and vascular protection, the involvement of estrogen receptors in mediating the protective effect of estrogen on hypertension-induced cardiovascular and renal injury is not fully explained. We aimed to investigate the effects of estrogen receptor (ER) agonists on oxidative injury, cardiovascular and renal functions of rats with renovascular hypertension (RVH). Female Sprague-Dawley rats were randomly divided as control and RVH groups, and RVH groups had either ovariectomy (OVX) or sham-OVX. Sham-OVX-RVH and OVX-RVH groups received either ER agonist diarylpropiolnitrile (1 mg/kg/day) or ER agonist propyl pyrazole triol (1 mg/kg/day) for 6 weeks starting at the third week following the surgery. At the end of the 9(th) week, systolic blood pressures were recorded, cardiac functions were determined, and the contraction/relaxation responses of aortic rings were obtained. Serum creatinine levels, tissue malondialdehyde, glutathione, superoxide dismutase, catalase levels, and myeloperoxidase activity in heart and kidney samples were analyzed, and Na+, K+-ATPase activity was measured in kidney samples. In both sham-OVX and OVX rats, both agonists reduced blood pressure and reversed the impaired contractile performance of the heart, while ER agonist improved renal functions in both the OVX and non-OVX rats. Both agonists reduced neutrophil infiltration, lipid peroxidation, and elevated antioxidant levels in the heart, but a more ER-mediated protective effect was observed in the kidney. Our data suggest that activation of ER might play a role in preserving the function of the stenotic kidney and delaying the progression of renal injury, while both receptors mediate similar cardioprotective effects., Scientific Research Project Commission of Marmara University (BAPKO) [SAG-A-010710-0221], This work was supported by the Scientific Research Project Commission of Marmara University (BAPKO); Project No: SAG-A-010710-0221.

WOS: 000430919000030, PubMed ID: 28478022, Objective: Oxygen free radicals are important components involved in the histopathologic tissue alterations observed during abdominal aortic aneurysms (AAAs). This study examined whether melatonin has protective or therapeutic effects against AAAs. Methods: Sprague-Dawley rats were divided into four groups. A CaCl2 model was used to induce AAA. Starting on the operation day (Mel+AAA+Mel group) or 4 weeks after the operation (AAA+Mel group), the rats received intraperitoneal melatonin (10 mg/kg/day) for 6 and 2 weeks, respectively. The control and AAA groups received vehicle for 2 weeks after the sham operation and AAA induction, respectively. Angiographic measurements were recorded at the beginning, week 4, and week 6 of the study. After decapitation, aorta tissues were taken for the measurement of malondialdehyde, 8-hydroxy-2'-deoxyguanosine, glutathione levels, and myeloperoxidase and caspase-3 activity. Matrix metalloproteinase (MMP)-2, MMP-9, tumor necrosis factor-a, and inducible nitric oxide synthase protein expressions were analyzed by Western blot technique. Aortic tissues were also examined by light microscopy. Results: CaCl2 caused an inflammatory response and oxidative damage indicated by rises in malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels. Myeloperoxidase and caspase-3 activities were increased, but glutathione levels were reduced. On the one hand, MMP-2, MMP-9, tumor necrosis factor-a, and inducible nitric oxide synthase protein expressions were increased in the vehicle-treated AAA group. On the other hand, melatonin treatment reversed all of these biochemical indices and histopathologic alterations. Conclusions: According to the data, although melatonin tended to reverse the biochemical parameters given on week 4, the preventive effect is more pronounced when given concomitantly with AAA induction because values were closer to the control levels., Marmara University Scientific Research Projects Commission [SAG-C-TUP-12114-0355], This project was supported by Marmara University Scientific Research Projects Commission (project no: SAG-C-TUP-12114-0355).

WOS: 000395036200008, PubMed ID: 27690684, Objective: To determine the levels of WISP1 and betatrophin in normal weight and obese women with polycystic ovary syndrome (PCOS) and to assess their relationship with anti-Mullerian hormone (AMH) levels, atherogenic profile and metabolic parametersMethods: In this prospective cross-sectional study, the study group was composed of 49 normal weighed and 34 obese women with PCOS diagnosed based on the Rotterdam criteria; 36 normal weight and 26 obese age matched non-hyperandrogenemic women with regular menstrual cycle. Serum WISP1, betatrophin, homeostasis model assessment of insulin resistance (HOMA-IR) and AMH levels were evaluated. Univariate and multivariate analyses were performed between betatrophin, WISP1 levels and AMH levels, metabolic and atherogenic parameters.Results: Serum WISP1 and betatrophin values were elevated in the PCOS group than in the control group. Moreover, serum WISP1 and betatrophin levels were higher in the obese PCOS subgroup than in normal weight and obese control subgroups. Multivariate analyses revealed that Body mass index, HOMA-IR, AMH independently and positively predicted WISP1 levels. Serum betatrophin level variability was explained by homocysteine, HOMA-IR and androstenedione levels.Conclusion: WISP1 and betatrophin may play a key role on the pathogenesis of PCOS.

WOS: 000394539800004, Platelets are sensitive cells and are easily activated by different stimulants in the circulation system. It is known that tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine and plays a role in inflammation. The role of TNF-a in the apoptotic process in blood platelets is unknown. In order to study the formation of apoptosis in platelets after incubation with TNF-alpha and/or ADP, several biomarkers were chosen: phosphatidylserine (PS) exposure and P-selectin binding; cGMP, Cyt-c, and Ca2+ levels and NOS activation; and gene and protein expression of caspase-3 and iNOS. Platelets were incubated with 100 pg/mL TNF-a and/or 50 mM iNOS specific inhibitor, such as at 1400 W for 1 h at 37 degrees C in the presence of 5 mu M ADP. According to the results, the levels of PS exposure and P-selectin binding were significantly higher in TNF-alpha + ADP platelets, which decreased with the addition of 1400 W. A significant induction in cGMP, Cyt-c, and Ca2+ levels was observed in platelets treated with TNF-alpha + ADP. On the other hand, the upregulation of the apoptotic gene caspase-3 and iNOS expression levels in TNF-alpha-treated and ADP-activated platelets was significantly reversed with the addition of 1400 W. These data demonstrate that TNF-alpha promotes iNOS expression through caspase-3 stimulation in human platelets, and its concomitance leads to the triggering of apoptosis-mediated inflammation upon platelet activation., Marmara University Research Unit [SAG-C-DRP-010710-0216]; Cumhuriyet University Research Unit [ECZ-001], The research was supported by the Marmara University Research Unit (Grant No. SAG-C-DRP-010710-0216) and was partly supported by the Cumhuriyet University Research Unit (Grant No. ECZ-001).

WOS: 000393171200001, PubMed ID: 27913135, This study evaluated the effect of mycophenolate mofetil (MMF) on uterine tissue preservation following ischaemia/reperfusion (I/R) injury. Uterine I/R injury was induced in rats by clamping the lower abdominal aorta and ovarian arteries for 30 min. Group I/R + V (n = 7) received vehicle alone while Group I/R + M (n = 7) received 20 mg/kg/day MMF. Control groups underwent sham surgery and received vehicle (Group C) or 20 mg/kg/day MMF (Group M) (n = 7 for both). Four hours after detorsion, uterine tissue 8-hydroxy-2'-deoxyguanosine (8-OHdG), glutathione, malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and serum ischaemia modified albumin (IMA) concentrations were measured. Histopathological analyses were performed. The I/R + M group showed significant reduction in serum IMA and uterine tissue 8-OHdG, MDA and MPO and significant increase in SOD concentrations compared with the I/R + V group, indicating a protective effect against I/R oxidative damage (P = 0.009, P = 0.006, P = 0.002, P = 0.003 and P = 0.009, respectively). Histopathological evaluation revealed MMF treatment resulted in significantly less tissue and cellular damage and apoptosis compared with the I/R + V group. These results indicate MMF is effective in attenuating uterine tissue damage and preventing apoptosis following uterine I/R injury, probably via anti-inflammatory and anti-oxidative action. (C) 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

WOS: 000398862500009, PubMed ID: 28394499, ObjectivesTo examine the possible protective effect of quercetin (QT), which is well known for its antioxidant and protective effects in circumstances of oxidative stress, on urinary bladder tissue in a rat model of ischemia/reperfusion (I/R) injury, which is a known factor for the development of lower urinary tract dysfunction partly mediated by the generation of free radicals causing oxidative damage. MethodsThirty male Sprague-Dawley rats were subjected to I/R injury through clamping the abdominal aorta for 30 min and then allowing reperfusion for the next 60 min. Quercetin (20 mg/kg; subcutaneously) or vehicle were given before ischemia and just before reperfusion. Findings of the isometric contraction studies in the organ bath and of the histological examinations along with oxidative stress markers were evaluated in bladder tissues. ResultsIncreased malondialdehyde (MDA) levels and myeloperoxidase (MPO) activities and decreased glutathione (GSH) levels and superoxide dismutase (SOD) activities in the I/R group were reduced by QT treatment. In the I/R group, pro-apoptotic marker caspase-3 was increased and anti-apoptotic bcl-2 protein was decreased, while QT treatment significantly reversed these parameters. In the I/R group contractile responses of the bladder strips to carbachol were significantly lower than those of the control group, which were reversed by QT treatment. ConclusionQuercetin treatment protects bladder tissue contractility against acute I/R injury by decreasing oxidative stress and apoptosis induced by I/R.

WOS: 000399742600012, PubMed ID: 27267804, Objective: To investigate Wnt1-inducible signaling pathway protein-1 (WISP1) levels and their correlation with metabolic parameters in pregnant women with gestational diabetes mellitus (GDM) and non-GDM healthy pregnant women. Materials and Methods: In this prospective cross-sectional study, the study group was composed of 62 women with GDM and 73 healthy pregnant women matched for age, body mass index (BMI) and gestational age. Blood samples were collected at 25-29th gestational week. Serum WISP1, betatrophin, glucose, fasting insulin, glycosylated hemoglobin A1c, total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, C reactive protein, alanine aminotransferase and creatinine levels were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) values was calculated. The level of significance was accepted as p

WOS: 000398070900028, PubMed ID: 27900560, Background The present study aimed to investigate the effects of Roux-en-Y gastric bypass (RYGB) and prosthesis placement on gastric emptying rate in conjunction with serum ghrelin-obestatin-leptin responses in non-obese rats with intact or denervated afferent innervation. Methods Under anesthesia, male Sprague-Dawley rats underwent either sham operation, RYGB, prosthesis, and/or Gregory cannula placement. Three weeks later, liquid or solid gastric emptying tests were performed and serum ghrelin, leptin and obestatin levels were measured. Results Both prosthesis placement and RYGB surgery delayed non-nutrient liquid emptying; while solid nutrient emptying was delayed only by RYGB. Nutrient-dependent (acid, hyperosmolal and peptone) delay in liquid emptying was abolished in rats with prosthesis. By vagal afferent denervation, delayed liquid emptying was abolished, while solid emptying was further delayed in rats with prosthesis. Ghrelin and obestatin levels were depressed in prosthesis-placed rats, but RYGB surgery had no impact on both levels. Leptin level was elevated in solid-food-given rats with prosthesis, but not changed in RYGB group, while it was reduced following liquid meal. All the changes observed in ghrelin, obestatin, or leptin levels in response to meal ingestion were reversed with vagal afferent denervation. Conclusions Both RYGB and prosthesis placement had delaying effects on gastric emptying rate of non-obese rats. Our results indicate that the short-term changes in gastric motility and hormone responses induced by volume reduction are reversed by afferent denervation, suggesting that sparing the vagal innervation could be essential for reaching optimum motility and hormone changes expected after bariatric surgery., Marmara University Research Fund, The authors acknowledge Merve Evren, PhD Candidate at Ege University Natural and Applied Sciences Department of Biotechnology, for the preparation of the excellent medical illustrations. This work was supported by a grant from Marmara University Research Fund.

WOS: 000341231200011, PubMed ID: 25039564, Ionizing radiation (IR) can induce cell damage and cell death through the reactive oxygen species generated by radiolytic hydrolysis. The present study was aimed to determine the possible protective effects of quercetin, a well-known antioxidant agent, against IR-induced bladder and kidney damage in rats. Sprague-Dawley rats were exposed to 8-Gy whole-abdominal IR and given either vehicle or quercetin (20 mg/kg, ip). Rats were decapitated at either 36 h or 10 days following IR, where quercetin or vehicle injections were repeated once daily, and kidney and bladder samples were obtained for the determination of myeloperoxidase and caspase-3 activities, an index of tissue neutrophil infiltration and apoptosis, respectively. Radiation-induced inflammation was evaluated through tissue cytokine, TNF-alpha levels. In order to examine oxidative DNA damage, tissue 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. All tissues were also examined microscopically. In the saline-treated irradiation groups, myeloperoxidase and caspase-3 activities, 8-OHdG and TNF-alpha levels were found to be increased in both tissues (p < 0.05). In the quercetin-treated-IR groups, all these oxidant responses were prevented significantly (p < 0.05). The present data demonstrate that quercetin, through its free radical scavenging and antioxidant properties, attenuates irradiation-induced oxidative organ injury, suggesting that quercetin may have a potential benefit in radiotherapy by minimizing the adverse effects and will improve patient care.

WOS: 000342223100005, PubMed ID: 24914105, It has been previously shown that acetylcholine (ACh) may affect pro-inflammatory and anti-inflammatory cytokines. The role of the cholinergic system in radiation-induced inflammatory responses and tissue damage remains unclear. Therefore, the present study was designed to determine the radio-protective properties of the cholinergic system in the ileum and the liver of rats. Rats were exposed to 8-Gy single-fraction whole-abdominal irradiation and were then decapitated at either 36 h or 10 d post-irradiation. The rats were treated either with intraperitoneal physiological saline (1 ml/kg), physostigmine (80 mu g/kg) or atropine (50 mu g/kg) twice daily for 36 h or 10 d. Cardiac blood samples and liver and ileal tissues were obtained in which TNF-alpha, IL-1 beta and IL-10 levels were assayed using ELISA. In the liver and ileal homogenates, caspase-3 immunoblots were performed and myeloperoxidase (MPO) activity was analyzed. Plasma levels of IL-1 beta and TNF-alpha increased significantly following radiation (P < 0.01 and P < 0.001, respectively) as compared with non-irradiated controls, and physostigmine treatment prevented the increase in the pro-inflammatory cytokines (P < 0.01 and P < 0.001, respectively). Plasma IL-10 levels were not found to be significantly changed following radiation, whereas physostigmine augmented IL-10 levels during the late phase (P < 0.01). In the liver and ileum homogenates, IL-1 beta and TNF-alpha levels were also elevated following radiation, and this effect was inhibited by physostigmine treatment but not by atropine. Similarly, physostigmine also reversed the changes in MPO activity and in the caspase-3 levels in the liver and ileum. Histological examination revealed related changes. Physostigmine experiments suggested that ACh has a radio-protective effect not involving the muscarinic receptors.

WOS: 000323107900003, PubMed ID: 23758074, Reactive oxygen metabolites play an important role in the ischemia/reperfusion (I/R)-induced tissue injury. This study was designed to investigate the possible protective effects of quercetin against I/R injury of the rat corpus cavernosum tissue. To induce I/R injury, abdominal aorta was clamped for 30 min and reperfused for 60 min. Quercetin (20 mg/kg) or vehicle was given before ischemia and just after reperfusion in the I/R group and in the sham-operated control group in which clamping was not performed. After decapitation, corpus cavernosum tissues were removed and either placed in organ baths or stored for evaluating biochemical parameters. Oxidative injury was examined by measuring lucigenin chemiluminescence (CL), nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities and caspase-3 protein levels. In the I/R group, contractile responses to phenylephrine and relaxation responses to carbachol were impaired significantly compared with those in the control groups, while quercetin treatment in I/R group reversed both of the responses. On the other hand, increase in lucigenin CL, NO, MDA levels and MPO and caspase-3 activities and decrease in GSH levels and SOD activity in the cavernosal tissues of the I/R group were also significantly reversed by quercetin treatment. Furthermore, observed distorted morphology with ruptured endothelial cells and vacuolization in the cytoplasm of cavernosal tissues of I/R no longer persisted in the quercetin-treated I/R group. Thus, our results suggested that treatment with quercetin may have some benefits in controlling I/R-induced tissue injury through its anti-inflammatory, anti-apoptotic, and antioxidant effects.

WOS: 000318810800005, PubMed ID: 23609809, Etodolac hydrazide and a novel series of etodolac hydrazide-hydrazones 315 and etodolac 4-thiazolidinones 1626 were synthesized in this study. The structures of the new compounds were determined by spectral (FT-IR, 1H NMR, 13C NMR, HREI-MS) methods. Some selected compounds were determined at one dose toward the full panel of 60 human cancer cell lines by the National Cancer Institute (NCI, Bethesda, USA). 2-(1,8-Diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-yl)acetic acid[(4-chlorophenyl)methylene]hydrazide 9 demonstrated the most marked effect on the prostate cancer cell line PC-3, with 58.24% growth inhibition at 105M (10 mu M). Using the MTT colorimetric method, compound 9 was evaluated in vitro against the prostate cell line PC-3 and the rat fibroblast cell line L-929, for cell viability and growth inhibition at different doses. Compound 9 exhibited anticancer activity with an IC50 value of 54 mu M (22.842 mu g/mL) against the PC-3 cells and did not display any cytotoxicity toward the L-929 rat fibroblasts, compared to etodolac. In addition, this compound was evaluated for caspase-3 and Bcl-2 activation in the apoptosis pathway, which plays a key role in the treatment of cancer., Scientific and Technical Research Council of Turkey (TUBITAK) [SBAG-HYD-339 (108S257)], This research was supported by The Scientific and Technical Research Council of Turkey (TUBITAK), Research Fund Project Number: SBAG-HYD-339 (108S257). The authors are grateful to Dr. Jurgen Gross from the Institute of Organic Chemistry, University of Heidelberg, for his generous help on obtaining HR-EI/FAB mass spectra of the synthesized compounds. We thank the Division of Cancer Research, National Cancer Institute, Bethesda, MD, USA, for the anticancer activity screening. Etodolac was supplied by Bilim Pharmaceutical Industry Inc.

WOS: 000316611700079, PubMed ID: 23519201, A series of novel N-(3-substituted aryl/alkyl-4-oxo-1,3-thiazolidin-2-ylidene)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamides 2a-e were synthesized by the addition of ethyl alpha-bromoacetate and anhydrous sodium acetate in dry ethanol to N-(substituted aryl/alkylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoro-methyl)- 1H-pyrazol-1-yl] benzene sulfonamides 1a-e, which were synthesized by the reaction of alkyl/aryl isothiocyanates with celecoxib. The structures of the isolated products were determined by spectral methods and their anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV NS5B RNA-dependent RNA polymerase (RdRp) activities evaluated. The compounds were also tested for gastric toxicity and selected compound 1a was screened for its anticancer activity against 60 human tumor cell lines. These investigations revealed that compound 1a exhibited anti-inflammatory and analgesic activities and further did not cause tissue damage in liver, kidney, colon and brain compared to untreated controls or celecoxib. Compounds 1c and 1d displayed modest inhibition of HCV NS5B RdRp activity. In conclusion, N-(ethylcarbamothioyl)-4-[5-(4-methylphenyl)- 3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (1a) may have the potential to be developed into a therapeutic agent., Research Fund of Marmara University [SAG-A-310510-0175]; National Institute of Health [CA153147], We wish to thank the National Cancer Institute for in vitro pharmacological screening. This work was generously supported by the Research Fund of Marmara University, project number: SAG-A-310510-0175 to S. G. K. HCV NS5B inhibition studies were supported by the National Institute of Health Research Grant CA153147 to N.K.-B. The authors are grateful to Jurgen Gross from the Institute of Organic Chemistry, University of Heidelberg, for his generous help on obtaining HR-EI mass spectra of the synthesized compounds.

WOS: 000406687000043, PubMed ID: 28215833, Background Testicular torsion is a common problem and, to date, there is no agent to preserve testicular function following detorsion. Platelet-rich plasma (PRP), with its rich growth factor composition, has proven beneficial in regenerative therapy. It is believed that PRP has not been studied in testis for ischemia/ reperfusion (I/R) injury. Objective This study investigated the effect of PRP in an I/R rat model 1 month after detorsion. Study design Of 24 adult male Spraguee-Dawley rats, 18 were randomly assigned into three groups, with six in each: control, I/R and I/R + PRP. The PRP was prepared from the remaining six. Each group underwent right orchiectomy. Ischemia was performed by rotating the left testis 720 degrees and fixing with a nylon suture for 4 h. Reperfusion occurred 4 h later by removing the suture, and PRP was administered at a dose of 10 ml (2000 x 10(9)/l) into the left testis via the intra-parenchymal route. Animals were sacrificed at the fourth week, and testes were taken for malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), myeloperoxidase (MPO), transforming growth factor beta (TGF-beta), and caspase-3 measurements. Results Ischemia/reperfusion caused a significant increase in MDA, MPO and caspase-3 activity, and significant decrease in GSH levels and SOD activity. The PRP treatment helped correct the alterations in SOD, caspase-3, and MPO activities and MDA levels. However, the mean MDA level and MPO activity were not totally restored compared with the controls. Serum testosterone levels of the I/R group were significantly lower compared with the control and I/R + PRP groups. TGF-b and caspase-3 protein expressions were significantly higher in the I/R group compared with the control group and were low with PRP administration compared with I/R groups (summary Table). Discussion The findings of the present study suggest that PRP, by inhibiting neutrophil infiltration and oxidative stress and increasing antioxidant defense, exerts protective effects on testicular tissues against I/R. This study had some limitations: a scoring system was not used in the assessment of spermatogenesis in the histopathological findings and specific testis cell types were not histologically assessed. Conclusions In light of the biochemical, histological and, especially, hormonal findings, intraparenchymal PRP injection may have a protective effect in testicular tissue against I/R injury.

WOS: 000380750600011, PubMed ID: 27083693, This study evaluated the effects of N-acetylcysteine (NAC) and enoxaparin on ovarian tissue preservation, ovarian reserve and oxidative damage following ovarian torsion/detorsion injury. Rats were divided into four groups (n = 6/group): control; ischaemia/reperfusion (I/R); I/R + NAC; I/R + enoxaparin. Twenty-four hours after detorsion, ovarian tissues were collected for histopathological analysis and measurement of tissue 8-OHdG, GSH, MDA, MPO and SOD concentrations, as well as pre- and post-operative circulating AMH concentrations. Administration of NAC resulted in more pre-antral follicles compared with enoxaparin treatment and haemorrhage and follicle cell degeneration were more pronounced in I/R + enoxaparin group than I/R + NAC group. Both NAC and enoxaparin led to a significant reduction in ovarian tissue 8-OHdG (P = 0.004 and P = 0.01, respectively) and MPO (P = 0.013 and P = 0.023, respectively) concentrations compared with I/R group, indicating a protective effect against I/R oxidative damage. Only NAC-treated animals showed a significant increase in GSH and SOD concentrations and decrease in MDA concentrations compared with I/R group (P = 0.007, P = 0.024 and P = 0.026, respectively). These results indicate that NAC is more effective than enoxaparin in minimizing ovarian damage and preserving ovarian reserve following ovarian torsion. (C) 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

WOS: 000375841100014, PubMed ID: 25775378, The aim of this study is to determine the cutaneous wound healing effects of the ethanol extract of Cotinus coggygria leaves in rats by excision wound model to provide scientific evidence for the traditional use of C. coggygria Scop. The levels of malondialdehyde, catalase, superoxide dismutase, glutathione and hydroxyproline were investigated in wound tissues. Histopathological examination was also performed. The hydroxyproline content of the granulation tissue and the glutathione levels were both significantly higher in the treatment group than in the control group (p < 0.05 for both); while the malondialdehyde levels were significantly lower in the treatment group (p < 0.05). These results were supported with histological results. The ethanol extract of C. coggygria Scop could be considered as an effective agent in wound healing in accordance with its traditional use., Marmara University Scientific Research Projects Committee [SAG-A-200611-0185], This study was supported by Marmara University Scientific Research Projects Committee [ grant number SAG-A-200611-0185].

WOS: 000387981700014, PubMed ID: 27664884, Background: The aim of our study was to investigate the antifibrotic and antioxidant effects of Myrtus communis subsp. communis (MC) extract against liver injury and fibrosis occurring in rats with biliary obstruction. Materials and methods: The rats were randomized into four groups (n = 8). Control group (C), MC-administrated group (MC), the bile duct ligation (BDL), and BDL + MC groups. MC was administered at a dose of 50 mg/kg a day orally for 28 days. In blood samples, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase levels, tumor necrosis factor-alpha, and interleukin-1 beta measurement were measured. Oxidative injury was examined by measuring luminol and lucigenin chemiluminescence, malondialdehyde and glutathione levels, superoxide dismutase and myeloperoxidase activities. Transforming growth factor-beta and hydroxyproline levels were measured for analyzing fibrosis. The hepatic injury was also analyzed microscopically. Results: Plasma total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-alpha, and interleukin-1 beta levels were found significantly high in the BDL group, while these values significantly decreased in the BDL group treated with MC. On the other hand, the glutathione and superoxide dismutase values significantly decreased in the BDL group compared to the control group but increased markedly in BDL + MC group compared to the BDL group. Malondialdehyde levels, myeloperoxidase activity, tissue luminol, lucigenin, transforming growth factor-beta, and hydroxyproline levels when compared with the control group increased dramatically in the BDL group and reduced the MC + BDL group. Conclusions: Our results suggest that MC protects the liver tissues against oxidative damage following BDL via its radical scavenging and antioxidant activities, which appear to involve the inhibition of tissue neutrophil infiltration. (C) 2016 Elsevier Inc. All rights reserved.

WOS: 000381362100004, PubMed ID: 26950289, Background Being an inevitable component of free tissue transfer, ischemia-reperfusion injury tends to contribute to flap failure. TNF- is an important proinflammatory cytokine and a prominent mediator of the ischemia-reperfusion injury. Etanercept, a soluble TNF- binding protein, has shown anti-inflammatory and anti-apoptotic effects in animal models of renal and myocardial ischemia-reperfusion injury. We have designed an experimental study to investigate the effect of etanercept on myocutaneous ischemia-reperfusion injury on transverse rectus abdominis myocutaneous flap model in rats.Methods Twenty-four male Sprague-Dawley rats were divided into 3 groups: In group 1 (sham), the TRAM flap was raised and sutured back without further intervention. In group 2 (control), the flap was raised and the ischemia-reperfusion protocol was followed. In group 3, etanercept (10 mg/kg, i.v.) was administered 10 minutes before reperfusion. At the end of the reperfusion period, biochemical and histolopathological evaluations were performed on serum and tissue samples.Results In the etanercept group the IMA and 8-OHdG levels (p=0.005 and p=0.004, respectively) were found significantly lower, and the GSH and SOD levels (p=0.01 and p

WOS: 000378389200128, PubMed ID: 27336623, Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets' tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight into the proteins that are involved in the platelets' activation response during ischemic stroke. It could be argued that this study lays the foundation for future mechanistic studies., Marmara University Research Unit Grants [SAG-C-DRP-010710-0216], This research was supported by Marmara University Research Unit Grants SAG-C-DRP-010710-0216. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

WOS: 000365505600011, Elimination of reactive oxygen species (ROS) can be an important strategy to improve healing of wounds. ROS have an effect on proliferation and cell survival signaling, which results in alteration of apoptotic pathways in cells. Melatonin has antioxidant properties on skin wounds. In our study, we investigated the effects of topical melatonin (3%, w/w) on apoptosis and p53 protein expression together with parameters of oxidative stress in a cutaneous excision wound model. Bcl-2 protein levels in wound tissue at the end of days 3, 7, and 14 were significantly increased, while caspase-3 activity and p53 protein expression in wound tissue at the end of days 3, 7, and 14 were also reduced with melatonin treatment during wound healing. On days 3 and 7 after the wound, malondialdehyde level was reduced and glutathione was increased with melatonin treatment. Melatonin decreased myeloperoxidase levels and increased hydroxyproline levels in wound tissue at the end of day 7. However, melatonin had no significant effect on percentage of wound closure. Considering our results, topical melatonin displays antioxidant, antiapoptotic, and p53-inhibitory effects, but these effects are not sufficient for the acceleration of wound closure., Marmara University Research Unit [SAG-D-050614-0237], This work was supported by the Marmara University Research Unit (Grant No: SAG-D-050614-0237). The authors would like to thank Prof Dr Goksel Sener for her contribution.

WOS: 000349006400018, PubMed ID: 25253099, Estrogen or combinational hormone therapy can protect to menopausal symptoms but exogenous estrogen therapy has some potential risks which in turns lead to the appearance of various diseases. In recent years plants with high phytoestrogen content are recommended as therapeutic agents for postmenopausal hormonal treatment. In this research, we investigated the effects of Momordica charantia (MC) on the estrogen production and E2 as well as anti-oxidative and anti-apoptotic role on the ovariectomy rat model. The rats were ovariectomized and fed on 2 g/kg of fruit extra of MC for 30 days by gavage. 17-beta estradiol (E2) and 8-OHdG levels in serum, markers of oxidative damage of ROS and ESR alpha, ESR beta and NF-kB gene levels were measured in uterus horn tissue. Caspase-3, caspase-9, TNF-alpha, IL-6, IL-10, Bcl-2 and Nf-kB proteins expression were assessed by western blotting. Structural changes in tissue were examined with H&E staining. MC administration also stimulated the E2 production and ESR alpha/ESR beta gene levels and the inhibited oxidative damage. Furthermore, MC treatment enhanced anti-apoptotic and anti-inflammatory process and tissue regeneration. Data herein support that MC directly regulates uterine estrogen response and may serve as a new phytoestrogenic substance for the treatment of post-menopausal symptoms., Marmara University Scientific Research Project Coordination [SAG-C-YLP 101012-0315], The research funded from Marmara University Scientific Research Project Coordination with grant number (SAG-C-YLP 101012-0315).

WOS: 000396525000087, PubMed ID: 27717860, OBJECTIVE To evaluate the protective effects of melatonin (Mel) on an ethylene glycol (EG)-induced nephrolithiasis model in rats. MATERIALS AND METHODS Thirty-two Wistar albino rats were divided into 4 groups: control, EG, prevention Mel (Mel + EG + Mel), and therapeutic Mel (EG + Mel). EG (0.75%) was added to drinking water to create nephrolithiasis model. The EG group received EG and the Mel + EG + Mel group received both EG and Mel for 8 weeks. In the EG + Mel group, EG is given for 8 weeks and Mel is given for the last 4 weeks of the experiment. At the end of experimental period, urine, blood samples, and tissues were collected. RESULTS In 24-hour urine samples, calcium, citrate, and creatinine levels were decreased and oxalate levels were increased in the EG group, whereas Mel prevention and Mel treatment reversed these parameters back to control levels. Malondialdehyde, glutathione activities, myeloperoxidase, superoxide dismutase levels, and caspase-3 activity showed improvements in the Mel-treated groups when compared with the EG group. 8-Hydroxydeoxyguanosine, matrix metalloproteinase 9 levels, N-acetyl-beta-glucosaminidase activity, and osteopontin mRNA expression were elevated in the EG group and decreased back to control levels in the Mel + EG + Mel and EG + Mel groups. Histological examination showed improvement in the Mel-treated groups when compared with the EG group. CONCLUSION Mel can prevent crystalluria and kidney damage due to crystal formation and aggregation. It can be considered as a potential prophylactic and protective agent in high-risk patients with urinary stone formation or recurrence if supported by further clinical studies. (C) 2016 Elsevier Inc.

WOS: 000333324400007, PubMed ID: 24552354, Oxidative stress plays an important role both in spinal cord injury (SCI) and erectile dysfunction (ED). The present study investigated the effects of melatonin and tadalafil treatment alone or in combination on SCI-induced ED. Male Wistar albino rats (n=40) were divided into five groups: sham-operated control and SCI-injured rats given either vehicle, melatonin (10mg/kg, i.p.), tadalafil (10mg/kg, p.o.) or a combination of melatonin and tadalafil. Spinal cord injury was induced using a standard weight-drop method. On Day 7 after SCI, intracavernosal pressure (ICP) was measured and all rats were decapitated. Cavernosal tissues were obtained to examine caspase 3, nitric oxide synthase (NOS), myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, as well as cGMP, nerve growth factor (NGF), malondialdehyde (MDA) and glutathione (GSH) levels. Spinal cord injury caused oxidative damage, as evidenced by increases in MDA and cGMP levels. In addition, MPO and caspase 3 activites were increased after SCI, whereas GSH and NGF levels and SOD activity were reduced. Melatonin effectively reversed these oxidative changes. Furthermore, in rats treated with both melatonin and tadalafil, the recoveries were more pronounced than in rats given either melatonin or tadalafil alone. The ICP/mean arterial pressure value in vehicle-treated SCI rats was significantly higher than in the control group, whereas in the tadalafil- and tadalafil+melatonin-treated groups have returned this value had returned to control levels. As an individual treatment, and especially when combined with tadalafil, a well-known agent in the treatment of ED, melatonin prevented SCI-induced oxidative damage to cavernosal tissues and restored ED, most likely due to its anti-oxidant effects.

WOS: 000327407300023, PubMed ID: 24057255, Stroke is a disease that affects the blood vessels that supply blood to the brain. Although platelets are implicated in the pathophysiology of stroke the mechanism is still not clear and there antiplatelet agents available for the prevention and treatment of stroke. We herein examined the relationship between the potential cytokine, TNF-alpha platelet activation and apoptosis in acute ischemic stroke patients. We selected 60 patients (mean age 57.9 +/- A 10.2 years) who had not taken any antiplatelet drugs for 14 days. A group of 45 participants (mean age 51.05 +/- A 9.07 years) were selected as the control group. For both the patients and for the control group, P-selectin (CD62p) and Annexin-V binding, cytochrome-c levels, caspase-3 gene expression and caspase-3 releasing and plasma TNF-alpha levels were measured in platelets. The results showed significant increase in plasma TNF-alpha and platelet Annexin-V, CD62p, cytochrome-c and caspase-3 gene expression in stroke patients compared to the control group. The data of this work suggests that inflammation may have a role in platelet apoptosis in stroke which may suggest a new aspect of the role of inflammation in the development of acute ischemic stroke., Marmara University Research Unit [SAG-C-DRP-010710-0216], This study was funded by the Marmara University Research Unit (Grant No. SAG-C-DRP-010710-0216).

WOS: 000321737300034, PubMed ID: 23490140, Background: Spinal cord injury (SCI) leads to an inflammatory response and generates oxidative stress, which has deleterious effects on the function of several organ systems, including the urinary bladder. The present study was designed to investigate the putative beneficial effect of quercetin against SCI-induced bladder damage. Materials and methods: In order to induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10 was used. Injured animals were given either 20 mg/kg quercetin or vehicle 15 min post injury and repeated twice daily for 7 d. After decapitation, bladder strips were placed in organ bath and isometric contractions to carbachol (10(-8) to10(-4) M) were recorded. In order to examine oxidative tissue injury, luminol chemiluminescence, nitric oxide, malondialdehyde, and glutathione levels and superoxide dismutase, myeloperoxidase, and caspase 3 activities of bladder tissues were measured along with histologic evaluations. Proinflammatory cytokines tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 were also assayed in blood samples. Results: In the injured animals, the contractile responses of the bladder strips were lower than those of the control group and were reversed by treatment with quercetin. On the other hand, increase in nitric oxide, malondialdehyde, luminol chemiluminescence levels, and myeloperoxidase and caspase 3 activities of tissues in the SCI group were significantly reversed by quercetin treatment. Similarly, plasma cytokine levels, which were elevated in the vehicle-treated SCI group, were reduced with quercetin treatment. Furthermore, treatment with quercetin also prevented the depletion of tissue glutathione levels and superoxide dismutase activity seen in the SCI group. Conclusions: According to the results, quercetin exerts beneficial effects against SCI-induced oxidative damage through its anti-inflammatory and antioxidant effects. (c) 2013 Elsevier Inc. All rights reserved.

WOS: 000312511800009, PubMed ID: 22986158, Spinal cord injury (SCI) leads to an inflammatory response that generates substantial secondary damage within the tissue besides the primary damage. Leukotrienes are biologically active 5-lipoxygenase products of arachidonic acid metabolism that are involved in the mediation of various inflammatory disorders including SCI. In this study, we investigated the possible protective effects of montelukast, a leukotriene receptor blocker, on SCI-induced oxidative damage. Wistar albino rats (n = 24) were divided randomly as control, vehicle- or montelukast (10 mg/kg, ip)-treated SCI groups. To induce SCI, a standard weight-drop method that induced a moderately severe injury at T10 was used. Vehicle or montelukast were administered to the injured animals 15 min after injury. At seven days post-injury, neurological examination was performed and rats were decapitated. Blood samples were taken to evaluate leukotriene 134 levels, and pro-inflmamatory cytokines (TNF-alpha, IL-1 beta) while in spinal cord and urinary bladder samples malondialdehyde (MDA), glutathione (GSH), luminol chemiluminescence (CL) levels and myeloperoxidase (MPO) and caspase-3 activities were determined. Tissues were also evaluated histologically. SCI caused significant decreases in tissue GSH, which were accompanied with significant increases in luminol CL and MDA levels and MPO and caspase-3 activities, while pro-inflammatory cytokines in the plasma were elevated. On the other hand. montelukast treatment reversed these parameters and improved histological findings. In conclusion, SCI caused oxidative tissue injury through the activation of pro-inflammatory mediators and by neutrophil infiltration into tissues, and the neuroprotective and antiapoptotic effects of montelukast are mediated by the inhibition of lipid peroxidation, neutrophil accumulation and proinflammatory cytokine release. Moreover, montelukast does not only exert antioxidant and antiapoptotic effects on the spinal cord, but it has a significant impact on the bladder tissue damage secondary to SCI. (C) 2012 Elsevier Inc. All rights reserved.