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    INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS
    (2023) Yüksel, Tuğba Nurcan; Yayla, Muhammed; Köse, Duygu; Ugan, Rüstem Anıl; Tokay, Erdem; Kılıcle, Pınar Aksu; Çadırcı, Elif
    Pomegranate peel contains bioactive ingredients such as flavonoids, ellagitannins, phenolics and proanthocyanidin compounds with high antioxidant activity. Pomegranate peel has antiapoptotic, antioxidant and anti-inflammatory effects due to its high punicalagin content. We aimed to determine the effect of pomegranate peel extract (PPE) on lipopolysaccharide (LPS)-induced uveitis. Sixty rats were seperated randomly into twelve groups (n = 5). The healthy group received intraperitoneal normal saline, the uveitis group received 200 ?g/kg LPS, the dexamethasone (DEX) group received 200 ?g/kg LPS plus 1 mg/kg DEX, the PPE100, PPE300 and PPE500 groups received 200 ?g/kg LPS plus 100, 300 and 500 mg/kg PPE, respectively. The eye tissues were collected at 3rd and 24th hour. and investigated molecularly (Relative quantification of gene expression), biochemically (Superoxide dismutase activity, Glutathione and Malondialdehyde levels) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Tumor Necrosis Factor-?, vascular endothelial growth factor, and Caspase-3 levels markedly decreased in a dose-dependent manner in the uveitic rats following PPE administration. PPE administration significantly ameliorated uveitic disorders in oxidative stress factors including Glutathione, Superoxide dismutase and Malondialdehyde, with its effects raising in a dose-dependent manner. PPE eliminated histopathological changes in eye tissues due to uveitis. PPE can be a promising agent by contributing to alternative preventive treatment methods for uveitis with its anti-inflammatory, antioxidative, antiapoptotic and antiangiogenic effects.
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    Protective effect of 5-HT7 receptor activation against glutamate-induced neurotoxicity in human neuroblastoma SH-SY5Y cells via antioxidative and antiapoptotic pathways
    (Pergamon-Elsevier Science Ltd, 2019) Yüksel, Tuğba Nurcan; Yayla, Muhammed; Halıcı, Zekai; Çadırcı, Elif; Polat, Beyzagül; Köse, Duygu
    Serotonin exerts anti-inflammatory, antioxidant and antiapoptotic effects through 5-HT7 receptors. The present study determined the role of 5-HT7 receptors in glutamate-induced neurotoxicity by using human SH-SY5Y neuroblastoma cells. The cells were pretreated with different concentrations of 5-HT7 receptor agonist LP44 and antagonist SB269970 for 60 min, followed by treatment with glutamate. Cell proliferation was measured using xCELLigence system. Treatment with all the concentrations of LP44 significantly protected the cells from the toxic effects of glutamate after 24, 48 and 72 h. Although 5-HT7 receptor expression was significantly upregulated in glutamate-treated cells, it was downregulated in LP44-pretreated cells. Furthermore, LP44 treatment significantly decreased malondialdehyde levels and increased superoxide dismutase activities and glutathione levels. Moreover, LP44 treatment significantly decreased tumor necrosis factor alpha (TNF-a) levels and inhibited caspase 3 and caspase 9 mRNA expression. In contrast, SB269970 treatment exerted an insignificant effect on oxidative stress, inflammation and apoptosis. These findings suggest that exogenous stimulation of the 54-1T7 receptors may be protective in glutamate-induced neurotoxicity and that 5-HT7 receptor agonists can be used as therapeutic agents for preventing glutamate-induced neurological disorders.
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    Protective Effects of Idebenone against Sepsis Induced Acute Lung Damage
    (Taylor & Francis Inc, 2022) Akpınar, Erol; Kutlu, Zerrin; Köse, Duygu; Aydın, Pelin; Tavacı, Taha; Bayraktutan, Zafer; Dinçer, Büşra; Yüksel, Tuğba Nurcan
    Background/Aims Sepsis is an uncontrolled systemic infection, withcomplex pathophysiology that may result in acute lung organ damage and cause multiple organ failure. Although much research has been conducted to illuminate sepsis's complex pathophysiology, sepsis treatment protocols are limited, and sepsis remains an important cause of mortality andmorbidity in intensive care units.Various studies have shown that idebenone (IDE) possesses strong antioxidant properties, which inhibit lipid peroxidation and protect cells from oxidative damage. The present study aimed to evaluate the protective effects of IDE against lung injury in a cecal ligation and puncture (CLP)-induced sepsis rat model. Methods Male albino Wistar rats were used. The animals were divided into a healthy control (no treatment), CLP, IDE control (200 mg/kg), and CLP + IDE subgroups (50 mg/kg, 100 mg/kg, and 200 mg/kg), with nine rats in each group.IDE was administered 1 h after CLP induction.To evaluate the protective effects of IDE, lung tissues were collected 16 h after sepsis for biochemical, immunohistochemical staining, and histopathological examination. Results IDE significantly ameliorated sepsis-induced disturbances in oxidative stress-related factors, with its effects increasing in accordance with the dose.IDE also abolished histopathological changes in lung tissues associated with CLP.Furthermore, interleukin 1 beta (IL-1 beta)and tumor necrosis factor-alpha (TNF-alpha) immunopositivity markedly decreased in the septic rats following IDE treatment. Conclusions IDE largely mitigated the inflammatory response in sepsis-induced lung injury by decreasing free radicals and preventing lipid peroxidation. The results suggest that IDE may represent a potential novel therapeutic drug for sepsis treatment.
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    Protective Effects of Ramelteon on Acute Lung Injury in Endotoxin-Induced Sepsis in Rats
    (2023) Yüksel, Tuğba Nurcan; Köse, Duygu; Gürbüz, Muhammet Ali; Halıcı, Zekai; Canbolat, Fadime; Bozgeyik, Esra
    Introduction: Sepsis is a life-threatening excessive systemic inflammatory reaction syndrome to infection that usually occurs in patients with bacteremia. The respiratory system is one of the structures most affected by acute organ damage. Melatonin plays an important role in re gulating various physiological functions of the body, including antioxidant and anti- inflammatory. Ramelteon (RAME) is the first melatonin receptor agonist confirmed for clinical use. The goal of this study is to determine the effects of RAME on endotoxin- induced septic lung injury in rats. Materials and Methods: Thirty-two female rats were separated randomly into four groups (n =8). Group healthy received intraperitoneal normal saline, group sepsis received intraperitoneally 10 mg/kg lipopolysaccharide (LPS), group sepsis+RAME2 received 10 mg/kg LPS plus 2mg/kg RAME, and group sepsis+RAME4 received 10 mg/kg LPS plus 4mg/kg RAME. RAME was administered by oral gavage 1 hour before LPS administration. The lung tissues were collected 12 hours after LPS administration and in vestigated molecularly (qRT- PCR analyses of Tumor Necrosis Factor-?, nuclear factor kappa-?, and interleukin 1-beta mRNA expression) and histopathologically (s taining with Harris Hematoxylin and Eosin Y). Results: TNF-?, NF- ??, and IL-1? levels significantly decreased dose-dependent in the septic rats following RAME administration. RAME admi nistration ameliorated histopathological injury in lung tissues due to sepsis. Conclusion: RAME ameliorated the inflammatory response in endotoxin-induced sepsis. These findings suggest that RAME can be a promising agent by contributing to alternative preventive treatment methods for sepsis with its anti- inflammatory effect.
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    The Effects of Agomelatine Treatment on Lipopolysaccharide-Induced Septic Lung Injuries in Rats
    (Aves, 2021) Köse, Duygu; Yüksel, Tuğba Nurcan; Halıcı, Zekai; Çadırcı, Elif; Gürbüz, Muhammed Ali
    Objective: We designed an experimental model of sepsis in rats to investigate the effects of agomelatine (AGO) on lung tissues using molecular and histopathological methods. Materials and Methods: In our experimental model, the 32 rats were divided into 4 groups: group 1: control group (HEALTHY); group 2: lipopolysaccharide group (LPS); group 3: LPS plus 50 mg/kg AGO group (LPS + AGO50); and group 4: LPS plus 100 mg/kg AGO group (LPS + AGO100). An LPS-induced sepsis model was performed to replicate the pathology of sepsis. Rats from all 4 groups were killed after 12 hours, and their lungs were quickly collected. To investigate the therapeutic strategy, we evaluated tumor necrosis factoralpha (TNF-alpha) and nuclear factor-kappa B (NF-kappa B) messenger RNA expressions by real-time polymerase chain reaction using molecular methods and lung tissue damage indicators using histopathological methods. Results: The expressions of TNF-alpha and NF-kappa B were reduced in the groups treated with AGO. The histopathology results supported the molecular results. Conclusion: In this experimental study, we demonstrated for the first time the positive effects of AGO on LPS-induced sepsis in lung tissue using molecular and histopathological methods, indicating that it contributes to the prevention of lung damage.