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Öğe Effect of trimetazidine against ovarian ischemia/reperfusion injury in rat model: A new pathway: JAK2/STAT3(Mashhad Univ Med Sciences, 2023) Yuksel, Tugba Nurcan; Halici, Zekai; Cadirci, Elif; Toktay, Erdem; Ozdemir, Bengul; Bozkurt, AyseObjective(s): Ovarian ischemia/reperfusion (I/R) is an extremely complex pathological problem that begins with oxygen deprivation, progresses to excessive free radical production, and intensifies inflammation. The JAK2/STAT3 signaling pathway is a multipurpose signaling transcript channel that plays a role in several biological functions. Trimetazidine (TMZ) is a cellular anti-ischemic agent. This study aims to investigate the effects of TMZ on ovarian I/R injury in rats. Materials and Methods: sixty four rats were divided into 8 groups at random: healthy(group1); healthy+TMZ20(group2); ischemia (I) (group 3); I+TMZ10(group4); I+ TMZ20(group5); I/R(group6); I/R+TMZ10(group7); I/R+TMZ20(group8). Vascular clamps were placed just beneath the ovaries and over the uterine horns for 3 hr to induce ischemia. The clamps were removed for the reperfusion groups, and the rats were reperfused with care to ensure that the blood flowed into the ovaries, subjecting them to reperfusion for 3 hr. TMZ was administered orally by gavage 6 and 1 hr before operations. At the end of the experiment, ovarian tissues were removed for biochemical, molecular, and histopathological investigation. Results: TMZ administration ameliorated ischemia/reperfusion-induced disturbances in GSH and MDA levels. TMZ treatment inhibited I/R-induced JAK2/STAT3 signaling pathway activation in ovarian tissues. TMZ administration also improved the increase in the mRNA expressions of IL1 beta, TNF-alpha, and NF-KB caused by ischemia/reperfusion injury. Moreover, TMZ treatment improved histopathologic injury in ovarian tissues caused by ischemia/reperfusion. Conclusion: TMZ treatment protected rats against ovarian ischemia/reperfusion injury by alleviating oxidative stress and inflammatory cascades. These findings may provide a mechanistic basis for using TMZ to treat ovarian ischemia-reperfusion injury.Öğe INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS(Trakya Univ Balkan Yerlesesi Enstituler Binasi, 2023) Yuksel, Tugba Nurcan; Yayla, Muhammed; Kose, Duygu; Ugan, Rustem Anil; Toktay, Erdem; Aksu Kilicle, Pinar; Cadirci, ElifPomegranate 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 mu g/kg LPS, the dexamethasone (DEX) group received 200 mu g/kg LPS plus 1 mg/kg DEX, the PPE100, PPE300 and PPE500 groups received 200 mu 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-alpha, 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.Öğe Protective effects of melatonin receptor agonists on endotoxin- induced uveitis in rats(Mashhad Univ Med Sciences, 2023) Yüksel, Tuğba Nurcan; Yayla, Muhammed; Köşe, Duygu; Halıcı, Zekai; Bozkurt, Erdinç; Toktay, ErdemObjective(s): Melatonin has an important role in regulating a variety of physiological functions of the body. We investigated the protective effects of Agomelatine (AGO) and Ramelteon (RAME) on Endotoxin-Induced Uveitis (EIU) in rats. Materials and Methods: 70 rats were randomly divided into fourteen groups. Healthy group normal saline, (IP), Uveitis group (200 pg/kg lipopolysaccharide (LPS), SC), DEX group (200 pg/kg LPS plus 1 mg/kg dexamethasone, IP), AGO20 group received 200 pg/kg LPS plus 20 mg/kg AGO, AGO40 group received 200 pg/kg LPS plus 40 mg/kg AGO, RAME2 group received 200 pg/kg LPS plus 2 mg/kg RAME, and group RAME4 received 200 pg/kg LPS plus 4 mg/kg RAME. Each group had two subgroups: the 3rd and 24th hour. The eye tissues were collected and investigated biomicroscopically (clinical manifestations and scoring, molecularly(qRT-PCR analyses of Tumor Necrosis Factor-alpha (TNF-alpha), vascular endothelial growth factor(VEGF), and Caspase 3 and Caspase 9 mRNA expression), biochemically (Superoxide dismutase activity, Glutathione, and Malondialdehyde levels) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Results: Melatonin receptor agonist treatment reduced the clinical score count of ocular inflammation in the uveitic rats. TNF-alpha, VEGF, Caspase 9, and Caspase 3 levels markedly decreased in the uveitic rats. Melatonin receptor agonists significantly ameliorated fixed changes in GSH, SOD, and MDA levels. Melatonin receptor agonists also ameliorated histopathological injury in eye tissues associated with uveitis. Conclusion: Melatonin receptor agonists ameliorated the inflammatory response in EIU. These findings suggest that melatonin receptor agonists may represent a potential novel therapeutic drug for uveitis treatment.Öğe Sıçanlarda Lipopolisakkarid Kaynaklı Akut Akciğer Hasarı Modelinde Nintedanibin NLRP3 Yoluyla Akciğerler Üzerindeki Etkileri(2024) Tanriverdiyeva, Gulchin; Aydın, Pelin; Aydın, Pelin; Toktay, Erdem; Çadırcı, Elif; Halıcı, ZekaiAmaç: Antifibrotik ve antitümör etkinliği gösterilmiş bir tirozin kinaz inhibitörü olan nintedanibin ciddi bir akciğer hastalığı olan akut akciğer hasarı (ALI) modelinde etkileri ve bu hastalığa karşı olası koruyucu etkinliğinin ortaya konulması ve NLRP3 / nükleer faktör kappa B (NF-?B) yolağı üzerine olası etkisinin incelenmesidir. Gereç ve Yöntem: Bu çalışmada 40 adet erkek Wistar albino sıçan kullanıldı. Bu sıçanlar eşit büyüklükte 5 gruba ayrıldı. Deney başlamadan önce, nintedanib seçilen gruplara 25 mg/kg, 50 mg/kg ve 100 mg/kg dozlarında oral olarak uygulandı. Nintedanib uygulamasından 24 saat, 12 saat veya 1 saat sonra, ALI için seçilen sıçanlara intratrakeal LPS uygulandı. İnterlökin (IL)-1? ve tümör nekroz faktörü-? (TNF-?) miktarları ELISA yöntemiyle, NLRP3, kaspaz-1, IL-1? ve NF-kB gen ekspresyonları ise revers-transkriptaz polimeraz zincir reaksiyonu yöntemiyle ölçüldü. Bulgular: Nintedanib uygulamasının, LPS ile indüklenen ALI’li sıçanların dokularında yüksek NLRP3, kaspaz-1, IL-1? ve NF-?B ekspresyonlarını ve IL-1? ve TNF-? sitokin düzeylerini düşürdüğü gözlendi. 50 mg/kg nintedanib alan akciğer hasarı grubunda yer alan sıçanlardan elde edilen bulgular, sağlıklı kontrol grubuna en çok benzeyen bulgulardı. Sonuç: ALI ile modellenen sıçanlarda nintedanibin NLRP3/NF-?B sinyal yolunu modüle ettiği ve ALI’nin etkilerini azalttığı gösterilmiştir.
