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    Agomelatine pretreatment prevents development of hyperglycemia and hypoinsulinemia in streptozotocin-induced diabetes in mice
    (Wiley, 2019) Ozcan, Mete; Canpolat, Sinan; Bulmus, Ozgur; Ulker, Nazife; Tektemur, Ahmet; Tekin, Suat; Ozcan, Sibel
    The main objective of this study was to investigate potential effectiveness of agomelatine pretreatment in the prevention of diabetes itself and encephalopathy, with a focus on brain tissue oxidative stress and inflammatory processes in streptozotocin (STZ)-induced diabetic mice. Interleukine-1 beta (IL-1 beta) and TACR1 (NK1), which is a tachykinine receptor, were used for the investigation of inflammation in the brain regions including raphe nucleus, periaqueductal gyrus (PAG), amygdala, and nucleus accumbens. The effects of agomelatine on total antioxidant capacity were also evaluated. In the in vitro part of the study, the effects of agomelatine on cell viability were investigated in dorsal root ganglion (DRG) neurons. Fasting blood glucose levels were measured 72 h after STZ injection to determine the diabetic condition. Agomelatine pretreatment prevented both hyperglycemia and hypoinsulinemia in STZ-treated mice. When STZ was injected to induce diabetes in mice, neither hyperglycemia nor hypoinsulinemia was developed in agomelatine pretreated mice and 6 weeks after development of diabetes, agomelatine treatment significantly decreased levels of IL-1 beta mRNA in raphe nucleus and nucleus accumbens. TACR1 mRNA levels were lower in raphe nucleus, PAG, and amygdala of agomelatine-treated diabetic mice. The increase in total antioxidant capacity after agomelatine administration may responsible for its beneficial effect in the prevention of diabetes. We showed that agomelatine reversed high glucose-induced cell viability decreases in DRG neurons. Both the antihyperglycemic and antioxidant effects of agomelatine might have contributed to the DRG neuron viability improvement. In conclusion, agomelatine seems to both prevent development of diabetes and reverse the encephalopathic changes caused by diabetes.
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    Effects of Different Levels of Restraint Stress on Bone-Implant Contact
    (Lippincott Williams & Wilkins, 2019) Bozoglan, Alihan; Dundar, Serkan; Yildirim, Tuba T.; Bulmus, Ozgur; Ertugrul, Abdullah Seckin; Bozoglan, Merve Y.; Tekin, Samet
    This study examined the effects of different levels of chronic restraint stress on bone-titanium implant contact in rats. This study included 32 adult female Sprague-Dawley rats. The machined surface titanium implants were surgically placed into the metaphyseal region of the rat tibias. Next, the rats were divided randomly into 4 groups, namely, control (CNT) (n = 8), low-restraint stress (LRS) (n = 8), medium-restraint stress (MRS) (n = 8), and high-restraint stress (HRS) (n = 8) groups. The rats in the CNT group received only the titanium implants surgically but did not receive any further treatment during the experimental period of 30 days. The rats in the LRS, MRS, and HRS groups were applied restraint stress for 1, 2, and 4 hours, respectively, daily for 28 days starting from day 2 after the surgery. At the end of the study period, the rats were sacrificed and their implants and the surrounding bone tissues were harvested for performing non-decalcified histological analysis. Moreover, blood samples were collected from the rats and were centrifuged for analyzing serum cortisol levels. Serum cortisol levels of the rats in the LRS, MRS, and HRS groups were higher than those of the rats in the CNT group (P<0.05). Moreover, serum cortisol levels of the rats in the HRS group were higher than those of the rats in the MRS and LRS groups (P<0.05). The extent of bone-implant contact was lower in the rats in the HRS group than in the rats in the CNT and LRS groups (P<0.05). These data suggest that the application of 4-hour chronic restraint stress during the 28-day experimental period impaired the bone-implant contact.
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    Effects of restraint stress and high-fat diet on osseointegration of titanium implants: an experimental study
    (Sociedade Brasileira De Pesquisa Odontologica, 2020) Dundar, Serkan; Bozoglan, Alihan; Bulmus, Ozgur; Tekin, Samet; Yildirim, Tuba Talo; Kirtay, Mustafa; Toy, Vesile Elif
    This study aimed to investigate the effects of chronic restraint stress (RS) and a high-fat diet (HFD) on the osseointegration of titanium implants in a rat model. After the surgical insertion of titanium implants into the metaphysis of the tibial bone, the rats were randomly divided into four equal groups (n = 8 each): control (CNT), restraint stress (RS), high-fat diet (HFD), and restraint stress plus high fat diet (RS-HFD). CNT: Rats received no further treatment during the 92-day experimental period. RS: Stress was applied to the rats beginning from two days after the implant surgery for one hour per day for the first 30 days, two hours per day for the next 30 days, and three hours per day for the last 30 days. HFD: Rats were fed a HFD for the following 90 days starting two days after surgery. RS-HFD: Rats were fed a HFD and RS was applied to rats for the following 90 days, starting two days after surgery. At the end of the experimental period, the rats were euthanized, and the implants and surrounding bone tissues were removed for histological analysis. Statistical analysis was performed by one way ANOVA and Bonferrroni tests. There were no significant differences in the bone-implant connection levels between the groups (p > 0.05), but in the HFD and RS-HFD groups, the bone filling ratios were found to be lower compared with the controls (p < 0.05) The data analyzed in this study suggest that an HFD with or without chronic RS adversely affected bone tissue in the rats during the 90-day osseointegration period.
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    Pinealectomy alters IFN-? and IL-10 levels in primary thymocyte culture of rats
    (C M B Assoc, 2018) Sahin, Zafer; Sandal, Suleyman; Yilmaz, Bayram; Bulmus, Ozgur; Ozdemir, Gokcen; Kutlu, Selim; Godekmerdan, Ahmet
    Melatonin, produced mainly by the pineal gland, has an immunomodulatory role. However, the effects of the pineal gland and/or melatonin on thymus cytokine levels such as interferon-gamma (IFN-gamma), interleukin (IL)-4, and IL-10 are not well known. Twenty-one male Wistar rats (220-250 gr) were randomly divided into three groups (n=7): intact control, sham, and pinealectomy. Primary thymocyte cultures were prepared from each group and dispensed into well plates as Control, DMSO (or vehicle), Sham-pinealectomy, Pinealectomy, Pinealectomy+10 mu M melatonin, and Pinealectomy+100 mu M melatonin. IFN-gamma, IL-4, and IL-10 concentrations were measured in the thymocytes (as nonstimulated and Concanavalin A-stimulated) after 24 h. IFN-gamma levels significantly increased and IL-10 levels significantly decreased in both media prepared from pinealectomized rats. There was no significant difference between the groups in terms of IL-4. In the pinealectomy+100 mu M melatonin group, IFN-gamma and IL-10 levels did not differ from the pinealectomy group. However, the dose of 100 mu M melatonin caused a decrease in levels of IFN-gamma in both thymocyte media and an increase in the concentration of IL-10 in Concanavalin A-stimulated thymocytes. In conclusion, pineal gland and or melatonin affect IFN-gamma and IL-10 levels in the thymus gland.
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    Pinealectomy alters ıfn-gamma and ıl-10 levels in primary thymocyte culture of rats
    (C m b assoc, 34 boulevard solferıno, 86000 poıtıers, france, 2018) Sahin, Zafer; Sandal, Suleyman; Yilmaz, Bayram; Bulmus, Ozgur; Ozdemir, Gokcen; Kutlu, Selim; Godekmerdan, Ahmet; Kelestimur, Haluk
    Melatonin, produced mainly by the pineal gland, has an immunomodulatory role. However, the effects of the pineal gland and/or melatonin on thymus cytokine levels such as interferon-gamma (IFN-gamma), interleukin (IL)-4, and IL-10 are not well known. Twenty-one male Wistar rats (220-250 gr) were randomly divided into three groups (n=7): intact control, sham, and pinealectomy. Primary thymocyte cultures were prepared from each group and dispensed into well plates as Control, DMSO (or vehicle), Sham-pinealectomy, Pinealectomy, Pinealectomy+10 mu M melatonin, and Pinealectomy+100 mu M melatonin. IFN-gamma, IL-4, and IL-10 concentrations were measured in the thymocytes (as nonstimulated and Concanavalin A-stimulated) after 24 h. IFN-gamma levels significantly increased and IL-10 levels significantly decreased in both media prepared from pinealectomized rats. There was no significant difference between the groups in terms of IL-4. In the pinealectomy+100 mu M melatonin group, IFN-gamma and IL-10 levels did not differ from the pinealectomy group. However, the dose of 100 mu M melatonin caused a decrease in levels of IFN-gamma in both thymocyte media and an increase in the concentration of IL-10 in Concanavalin A-stimulated thymocytes. In conclusion, pineal gland and or melatonin affect IFN-gamma and IL-10 levels in the thymus gland.
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    Protective Effect of Pomegranate Juice on Lead Acetate-Induced Liver Toxicity in Male Rats
    (Pera Yayincilik Hizmetleri, 2024) Pekmez, Hidir; Annac, Ebru; Bulmus, Ozgur; Zencirci, Buesra; Aydin, Merve; Aydin, Ali
    Objective: Lead has been reported to cause oxidative stress in liver tissues and cause histopathological changes. Studies have shown that pomegranate juice has antioxidant properties that prevent oxidative stress. In this study, the harmful effects of lead acetate on rat liver tissue and the efficacy of pomegranate juice against these effects were investigated. Methods: 28 male Wistar albino rats were divided into four groups: control, lead acetate (50 mL/ kg), pomegranate juice (1 mL/kg), and lead acetate + pomegranate juice (50 mL/kg+1 mL/kg). Lead acetate and pomegranate juice were administered orally. Results: When compared with the control group, it was seen that the lead acetate had an increase in the malondialdehyde level and a decrease in reduced Glutathione, Glutathione S-transferase, and Carboxylesterases. Group lead acetate + pomegranate juice had a reduction in malondialdehyde level and an increase in Glutathione, Glutathione S-transferase, and Carboxylesterases compared with the group lead acetate. The lead level of group lead acetate + pomegranate juice decreased compared to the group lead acetate. Cellular degeneration and irregular hepatic cords were observed in group lead acetate's liver tissue, and the negative changes were lost in group lead acetate + pomegranate juice. Conclusion: It was observed that pomegranate juice had a protective effect against liver toxicity caused by lead acetate.
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    The protective effects of pomegranate juice on lead acetate-induced neurotoxicity in the male rat: A histomorphometric and biochemical study
    (Wiley, 2022) Annac, Ebru; Uckun, Mirac; Ozkaya, Ahmet; Yologlu, Ertan; Pekmez, Hidir; Bulmus, Ozgur; Aydin, Ali
    The purpose of this study was to investigate the potential side-effects of lead acetate (LA), which is toxic to the nerves, blood and muscles, in the rat brain. The neuroprotective effects of pomegranate juice (PJ) against LA exposure were also observed. The experiment involved 28 male Wistar albino rats aged 12 weeks. These were divided into four groups: Control, PJ, LA and LA+PJ. Stereological techniques were employed to determine hippocampal volume in each rat brain. Biochemical investigations and histopathological examinations were also performed. Analysis demonstrated a significant decrease in hippocampal volume in the LA group compared to the control group (p < .05). The stereology results also indicated that PJ has protective effects when compared with the LA and LA+PJ groups. A significant increase was also determined in malondialdehyde (MDA) levels and glutathione S-transferase (GST) activity in the LA group compared to the control group, in contrast to glutathione (GSH) levels and carboxylesterase (CaE) and acetylcholinesterase (AchE) activities. MDA and GST activity decreased significantly in the LA+PJ group compared to the LA group in contrast to GSH levels and CaE and AchE activities. Histopathological examination revealed a number of degenerative changes in the LA group. Exposure to LA adversely affects the hippocampus on the male rat brain. It might also be suggested that PJ may ameliorate these deleterious effects.