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Öğe Diyabette Leptin Hormonun Olası Etkileri(2019) Taşkın, Eylem; Güven, Celal; Kaya, Salih Tunç; Sevgiler, YusufŞeker hastalığı olarak bilinen diyabet, çeşitli komplikasyonları (kalp ve dolaşım hastalıkları, kanser ve buna benzerhastalıklar) beraberinde getiren, insan hayatını olumsuz yönde etkileyen metabolik bir hastalıktır. Genel olarakdiyabet tip I ve tip II olmak üzere iki büyük alt grupta toplanan bir hastalıktır. Tip I diyabette beta (?) hücrelerininapoptoz ile kaybı insülin salgısının azalmasında önemli bir mekanizmadır. Leptin de insülin gibi antiapoptotik veproliferatif hormonlardan biridir. Dahası düşük leptin ve insülin tedavisinin sadece yüksek doz insülin kullanımınaoranla kan şekerinin tamponlanmasında daha etkili olduğu bildirilmektedir. Fakat leptinin tip I diyabetteki buetkisi/etkileri hala gizemini korumaktadır. Leptinin tip I diyabetteki önemli etkisinden biri de yağların ?oksidasyonunun artmasına neden olarak, kan şekerinin tamponlanmasını da sağları. Bu da insülin direncininoluşmasının azalmasına neden olmaktadır. Ayrıca leptinin insülinin anabolik etkilerini taklit ettiği gibi diyabettemeydana gelen ketoasidozu önlediği de vurgulanmaktadır. Dolayısıyla leptin tedavisi, zorunlu yüksek doz insülinkullanımı azaltılmasına olanak tanıyabilmektedir. Bu derleme, literatürdeki leptin ve diyabet arasındaki bukarmaşık ilişkinin mekanizmasının aydınlatılmasında önemli bir katkı sağlayabilecek potansiyele sahiptir.Öğe Düzce ilinde bulunan arıcılık işletmelerinde görülen koloni kayıplarının, bal arısı hastalık ve zararlılarının ve mücadele yöntemlerinin araştırılması(2013) Kekeçoğlu, Meral; Göç, Pınar Rasgele; Acar, Filiz; Kaya, Salih TunçBu çalışma Düzce ili ve ilçelerindeki arı yetiştiricilerinin koloni kayıpları, bal arısı hastalık ve zararlılarına yönelik sorunlarının saptanması ve çözüm önerilerinin getirilmesi amacıyla 2012 yılı Nisan-Temmuz ayları arasında yürütülmüştür. Düzce merkez ve 7 ilçesinin 245 köyünde bulunan 412 arıcıyla yüzyüze görüşülerek anket çalışması yapılmıştır. Araştırma sonuçlarına göre; işletmelerin % 81.20si kışlatma kaybı yaşarken, % 18.80inde kışlatma kaybı görülmemiştir. Kışlatma kayıplarının % 39.80inin ana kaybından, % 23.80inin Varroadan, % 21.90ının açlıktan, % 3.90ının yağmacılıktan ileri geldiği bildirilmiştir. İşletmelerin % 89.80inde Varroa, % 51.60ında Güve, % 18.20sinde Nösema ve % 13.11inde Amerikan yavru çürüklüğü hastalığı mevcuttur. Arıcıların hastalıklara karşı kullandıkları ilaçların seçimini % 47.80inin kendi bilgilerine göre, % 26.30unun veterinere danışarak, % 35.45inin başkalarının tavsiyesine göre, yaptıkları belirlenmiştir. Varroa, Nösema ve Amerikan yavru çürüklüğünün tedavisinde en fazla kullanılan ilaçlar sırasıyla Amitraz (% 65.75), Fumidil-B (% 54.42) and Apimisin (% 43.59)dir. Bu araştırmadan elde edilen sonuçlara göre, koloni kayıplarının en önemli sebebi kışlatmadır. Arıcıların bal arılarının kışa hazırlanması, koloni yönetimi, arı hastalık ve zararlılarının teşhis ve tedavisi konusunda eksikliklerinin olduğu saptanmıştır.Öğe Effect of ATP-dependent channel modulators on ischemia-induced arrhythmia change depending on age and gender(Royal Soc Medicine Press Ltd, 2013) Bozdoğan, Ömer; Kaya, Salih Tunç; Yaşar, Selçuk; Orallar, HayriyeThe number of ATP-dependent potassium channels in myocardial cells has been previously shown to change depending on gender and age. Different effects of the ATP-dependent potassium channel blocker, glybenclamide and ATP-dependent potassium channel opener, pinacidil on ischemia or reperfusion-induced arrhythmia observed in various research might depend on different ages and genders of the animals used. The aim of this study is to research the effect of ATP-dependent potassium channel modulators on ischemia-induced arrhythmia in animals of different ages and genders. Sprague-Dawley rats of different ages and genders were used in this study. Ischemia was produced by the ligation of the left coronary artery for 30 min. Electrocardiogram (ECG), blood pressure, infarct area and blood glucose were determined during the 30 min of ischemia. An arrhythmia score from an ECG recorded during 30 min of ischemia was determined by examining the duration and type of arrhythmia. Different effects of glybenclamide and pinacidil on the arrhythmias were observed in male and female young and middle-age rats. Pinacidil decreased the infarct zone in younger female rats, but differences in the type and length of ischemia-induced arrhythmias between females and males disappeared in older age. The results of this study showed that the effect of ATP-dependent potassium channel modulators on ischemia-induced arrhythmia changed due to the age and gender of rats.Öğe The effect of intermittent fasting and water restriction on myocardial ischemia/reperfusion-induced arrhythmia in rats(Tubitak Scientific & Technical Research Council Turkey, 2012) Kaya, Salih Tunç; Bozdoğan, ÖmerAim: To investigate the effect of intermittent fasting and water restriction on ischemia/reperfusion-induced arrhythmias. Materials and methods: Six minutes of ischemia followed by 6 min of reperfusion was produced by the ligation and then releasing of the left coronary artery. Intermittent fasting and water restriction were applied during 1 month for 12 h/day. The duration, type, and incidence of arrhythmias during reperfusion and the survival rate at the end of reperfusion were determined and compared. Results: The score of arrhythmia that was determined using the type and duration of arrhythmia did not show significant differences among groups. The arrhythmic period was significantly longer in animals subjected to 1 month of intermittent water and food restriction. The risk of ischemic zone was found to be significantly larger in the animals subjected to 1 month of normal feeding after 1 month of food and water restriction. Conclusion: Intermittent fasting and water restriction was not found to be effective in decreasing the arrhythmia that occurred during 6 min of myocardial reperfusion in rats. Since there is no other study compatible with the present study, further research is required on the effect of intermittent fasting and water restriction on ischemia/reperfusion-induced arrhythmia and on the risk of an ischemic zone.Öğe The Effect of Long Termand Acute Administration of Genistein on Ischemia-reperfusion-induced Arrhythmia(Wiley-Blackwell, 2016) Ekşioğlu, Didem; Erim, Firdevs; Bozdoğan, Ömer; Özarslan, Oğulcan Talat; Orallar, Hayriye Soytürk; Kaya, Salih Tunç; Yaşar, Selçuk…Öğe The Effect of Resveratrol and Glibenclamide on Ischemia/Reperfusion Induced Arrhythmias in STZ-induced Diabetic Rats(Wiley-Blackwell, 2016) Kaya, Salih Tunç; Özaslan, Oğulcan Talat; Ekşioğlu, Didem; Erim, Firdevs; Yaşar, Selçuk; Bozdoğan, Ömer…Öğe The effects of ATP-dependent potassium channel opener; pinacidil, and blocker; glibenclamide, on the ischemia induced arrhythmia in partial and complete ligation of coronary artery in rats(Mashhad Univ Med Sciences, 2015) Yaşar, Selçuk; Bozdoğan, Ömer; Kaya, Salih Tunç; Orallar, Hayriye SoytürkObjective(s): Electrical inhomogeneity between ischemic and non ischemic myocardium is the basis of arrhythmia which occurs following coronary artery occlusion. The leakage of potassium from the ischemic region to the non ischemic region is very effective in the generation of these arrhythmias. The aim of this study is to research the effect of ATP-dependent potassium (K-ATP) channel blocker (glibenclamide) and opener (pinacidil) on ischemia induced arrhythmia in the presence of small and large infarct sizes. Materials and Methods: In this study Sprague-Dawley male rats of 8-9 months of age were used. Ischemia was produced by the partial ligation of left coronary artery ramus descending (PL) for smaller infarct and complete ligation of this artery (CL) for larger infarct for 30 min. The arrhythmia score which was calculated from the duration and type of arrhythmia was significantly higher in animals which had a larger infarct area than the animals which had a smaller infarct. Results: Glibenclamide increased the rate of arrhythmia in animals having smaller infarct but not in animals having larger infarct. Pinacidil did not affect the occurrence of arrhythmia in either group. There was a significant difference in the infarct size and risk of infarct zone between animals which had small and large infarct sizes. The effect of glibenclamide and pinacidil on the arrhythmias differed depend on decrease of infarct size. Conclusion: Glibenclamide is not effective to decrease ischemia induced arrhythmia in the presence of small and pinacidil in large ischemic zone.Öğe Effects of diazoxide on streptozotocin induced beta cell damage via HSP70/HSP90/TLR4/AMPK signaling pathways(Taylor & Francis Ltd, 2023) Kaya, Salih TunçI investigated the effects of diazoxide, a mitochondrial potassium channel opener, on streptozotocin (STZ) induced pancreatic beta cell damage via the HSP70/HSP90/TLR4/AMPK signaling pathways in vitro. I used the pancreatic beta cell line, 1.1B4, to create four groups: control, STZ treated, diazoxide treated, STZ + diazoxide treated. The STZ treated cells were exposed to 20 mu M STZ for 2 h with or without 100 mu M diazoxide for 24 h. Total antioxidant status (TAS), total oxidant status (TOS), cell viability and mitochondrial membrane potential (MMP) were measured. Expression of ATP-sensitive potassium channel (K-ATP) subunits, heat shock protein-70 (HSP70), heat shock protein-90 (HSP90), toll-like receptor 4 (TLR4), AMP-activated protein kinase (AMPK) and some apoptotic proteins were detected using western blotting. Apoptosis was assessed using TUNEL staining. STZ increased TOS and OSI in the pancreatic beta cells; however, diazoxide failed to improve oxidative stress. Also, STZ increased tunnel positive cells in the pancreatic beta cells. Diazoxide decreased the tunnel positive cells in the STZ treated beta cell. STZ decreased MMP; however, diazoxide did not normalize MMP in the STZ induced beta cells. Diazoxide increased the HSP70:HSP90 protein expression ratio. STZ decreased expression of AMPK and subunits of K-ATP channel and increased the expression of caspase-3 and TLR4 protein; diazoxide normalized the expression of all proteins studied. K-ATP channel opening by diazoxide protects pancreatic beta cells against STZ toxicity via HSP70/HSP90/TLR4/AMPK signaling.Öğe Herbal medicine in diabetes mellitus with cardiovascular diseases(Springer International Publishing, 2019) Kaya, Salih Tunç; Güven, Celal; Taşkın, Eylem[No abstract available]Öğe HMGB1: Functions, inhibitors and clinical significance(Nova Science Publishers, Inc., 2022) Taşkın, E.; Güven, Celal; Kaya, Salih TunçDamage-associated molecular patterns (DAMPs), a term also known as alarmins coined by Walter G. Land, Seong, and Matzinger, are endogenous danger molecules that are released from damaged or dying cells and activate the innate immune system by interacting with pattern recognition receptors (PRRs). One of the most well-known DAMPs is High Mobility Group Box-1 (HMGB1), the name being such due to its very fast movement in gel electrophoresis. Importantly, HMGB1 has been shown to contribute to the pathogenesis of various diseases including myocardial ischemia/reperfusion injury, epilepsy, diabetes, multiple sclerosis, cancer, as well as hepatic steatosis, and fatty liver disease. There are three sections in the book. The first section is named HMGB1 and Cancer, including two chapters. One of the chapters is focused on HMGB1 in cancer therapy and managing COVID-19 infection, as well as multiple sclerosis. The second chapter in the first section is the crosstalk between cancer and myocardial ischemia/reperfusion injury (MIR) through HMGB1 via ferroptotic cell death. The second section is HMGB1 and metabolic interactions, consisting of two chapters. The first chapter is HMGB1 and inflammation in adipose tissue, resulting in insulin resistance and type 2 diabetes. The second chapter in the second section sums up recent data related to HMGB1 and liver injury, e.g., drug-induced liver injury, alcoholic liver disease, non-alcoholic fatty liver disease, viral hepatitis, sepsis, and acute chronic liver failure, hepatocellular death through oxidative stress, inflammatory signaling, and autophagy in hepatocytes. The third section is about HMGB1 and neurodegenerative diseases. The section contains four chapters. The first chapter in the section evaluates HMGB1 and its antagonist in brain disorders, including epilepsy, headache, neuroimmunological disorders, neurodegenerative disorders, and stroke. The second chapter in the third section is about the role of HMGB1 on post-brain injury, including potential mechanisms and therapeutic opportunities as well. The third chapter in the third section evaluates the interaction of HMGB1 and Multiple sclerosis via TLR4/NF-?B signaling pathway, leading to the release of proinflammatory cytokines causing an inflammatory response. The last chapter aims to explain the effects of HMGB1 on epilepsy. © 2023 by Nova Science Publishers, Inc. All rights reserved.Öğe HMGB1’in Kanser ve Tedavisiyle İlişkisi(2019) Taşkın, Eylem; Güven, Celal; Kaya, Salih Tunç; Sevgiler, YusufYüksek mobilite grup kutusu 1 (HMGB1) histon olmayan DNA proteini olup, kısaca DAMP olarak ifade edilen(Damage-associated molecular pattern) tehlike sinyali veya alarmı olarak görev yapar. Hasarlanmış veya kanserlihücrelerden salınan HMGB1, gelişmiş glikasyon son ürünleri için reseptör (RAGE) ve Toll benzeri reseptörlerine(TLRs) bağlanarak mitojenle aktive olan kinaz (MAPK)’ları aktive ederek hücre içi etkilerini oluşturur. HMGB1kanser ilaçlarına karşı gelişen dirençte önemli rol oynar. Aynı zamanda, yumuşak doku kanserlerine karşıkullanılan ilaçlardan biri olan adriyamisinin (ADR) neden olduğu kalp yetmezliğinin gelişiminde de önemli roloynağına dair kanıtlar mevcuttur. Dolayısıyla HMGB1 kanser tedavisinde ilaçlara karşı gelişen direncin ve/veyailacın toksik etkisine karşı iyi bir terapötik ajan adayıdır. Bu derlemenin amacı, HMGB1 ile kanser ve tedavisindekullanılan bir ilaç olan ADR arasındaki ilişkiyi açıklamaktır.Öğe The Identification of Intracellular Signalling Pathway Through DHMGB1/TLR2 Axis on Myocardial Ischemia/Reperfusion Injury-Induced Apoptosis(Wiley, 2022) Güven, Eylem Taşkın; Güven, Celal; Kaya, Salih Tunç; Keles, Ayse Ikinci; Destegul, Dilek; Pelit, Aykut; Günay, İsmail[Bastract Not Available]Öğe Inhibition of Angiotensin-II Production Increases Susceptibility to Acute Ischemia/Reperfusion Arrhythmia(Int Scientific Literature, Inc, 2016) Taşkın, Eylem; Tuncer, Kadir Ali; Güven, Celal; Kaya, Salih Tunç; Dursun, NurcanBackground: Myocardial ischemia and reperfusion lead to impairment of electrolyte balance and, eventually, lethal arrhythmias. The aim of this study was to investigate the effects of pharmacological inhibition of angiotensin-II (Ang-II) production on heart tissue with ischemia-reperfusion damage, arrhythmia, and oxidative stress. Material/Methods: Rats were divided into 4 groups: only ischemia/reperfusion (MI/R), captopril (CAP), aliskiren (AL), and CAP+AL. The drugs were given by gavage 30 min before anesthesia. Blood pressure and electrocardiography (ECG) were recorded during MI/R procedures. The heart tissue and plasma was kept so as to evaluate the total oxidant (TOS), antioxidant status (TAS), and creatine kinase-MB (CK-MB). Results: Creatine kinase-MB was not different among the groups. Although TAS was not affected by inhibition of Ang-II production, TOS was significantly lower in the CAP and/or AL groups than in the MI/R group. Furthermore, oxidative stress index was significantly attenuated in the CAP and/or AL groups. Captopril significantly increased the duration of VT during ischemia; however, it did not have any effect on the incidence of arrhythmias. During reperfusion periods, aliskiren and its combinations with captopril significantly reduced the incidence of other types of arrhythmias. Captopril alone had no effect on the incidence of arrhythmias, but significantly increased arrhythmias score and durations of arrhythmias during reperfusion. MAP and heart rate did not show changes in any groups during ischemic and reperfusion periods. Conclusions: Angiotensin-II production appears to be associated with elevated levels of reactive oxygen species, but Ang-II inhibitions increases arrhythmia, mainly by initiating ventricular ectopic beats.Öğe The protection of resveratrol and its combination with glibenclamide, but not berberine on the diabetic hearts against reperfusion-induced arrhythmias: the role of myocardial K-ATP channel(Taylor & Francis Ltd, 2019) Kaya, Salih Tunç; Bozdoğan, Ömer; Özarslan, Talat O.; Taşkın, Eylem; Eksioğlu, Didem; Erim, Firdevs; Yaşar, SelçukContext: Cardiovascular dysfunctions such as life-threatening arrhythmias are one of the main reasons of mortality and morbidity in diabetic patients Objective: We aimed to investigate the long-term effects of resveratrol, berberine and glibenclamide combinations on the ischemia/reperfusion (I/R) induced arrhythmias in streptozotocin (STZ)-induced diabetic rats and to investigate the role of myocardial K-ATP channel in the possible anti-arrhythmic actions of the treatments. Methods: Two days after induction of diabetes, diabetic rats were treated with resveratrol [5 mg/kg, intraperitoneally (i.p.)], berberine (10 mg/kg, i.p) and glibenclamide (5 mg/kg, i.p) for 6 weeks. On the 43th day, experimental animals were subjected to 6-min ischemia and 6-min reperfusion in vivo. Results: The protein expression of Kir6.2 subunits was downregulated in the diabetic hearts. However, all drug treatments restored the protein expression of Kir6.2 subunits. Resveratrol alone and its combination with glibenclamide decreased the arrhythmia score, the arrhythmic period and the incidence of other types of arrhythmias during the reperfusion period. Conclusions: The combination of resveratrol with glibenclamide may alleviate reperfusion-induced arrhythmias via an underlying mechanism not be only associated with the restoration of the protein expression of Kir6.2 subunits but also associated with the other subunits or ion channels underlying cardiac action potential.Öğe Protective effect of propolis on myocardial ischemia/reperfusion injury in males and ovariectomized females but not in intact females(Wiley, 2022) Kaya, Salih Tunç; Ağan, Kağan; Fulden-Ağan, Aydan; Agyar-Yoldaş, Pınar; Özarslan, Talat Oğulcan; Kekeçoğlu, Meral; Kaya, AdnanThe aim of this study is to investigate the effect of propolis, which may have estrogenic effects, on myocardial ischemia/reperfusion (mI/R) injury not only in male rats but also in intact and ovariectomized (ovx) female rats. Six groups were formed: untreated males (n = 8), treated males (n = 9), untreated intact females (n = 9), treated intact females (n = 10), untreated ovx females (n = 10), and treated ovx females (n = 8). An alcoholic extract of a single dose of propolis (200 mg/kg) was administered orally daily for 14 days. Thirty minutes of ischemia and 120 min of reperfusion were performed. Blood pressure, heart rate, arrhythmias (ventricular premature contraction [VPC], ventricular tachycardia [VT], ventricular fibrillation [VF]), and myocardial infarct size were evaluated. Total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and 17 beta-estradiol (E2) were measured. The untreated females showed more resistance to mI/R injury than the untreated males, as evidenced by lower duration, incidence, and score of arrhythmias, and smaller infarct size (p < .05). After ovx, this resistance disappeared. Propolis improved these values in treated males and treated ovx females (p < .05). Propolis increased TAS in treated males and decreased TOS in treated ovx females as well as elevated SOD in all treated groups (p < .05). Propolis decreased E2 level in treated intact females; however, it increased E2 level in treated ovx females (p < .05). The results revealed that propolis could protect the heart against mI/R injury in males and ovx females. Practical applications It is known that the female heart has an increased sensitivity to myocardial ischemia/reperfusion (mI/R) injury due to estrogen deficiency and/or estrogen deprivation following menopause or surgical removal of the ovaries. Propolis has the potential to mimic estrogen under physiological and pathophysiological conditions, as well as its antioxidant property. The results indicated that propolis decreased myocardial infarct size, arrhythmia score, arrhythmia duration, and incidence in ovariectomized female rats and male rats. In addition, the present results demonstrated that an alcoholic extract of propolis as a natural product can effectively maintain the resistance of female heart to mI/R injury after estrogen deficiency.Öğe Rhododendron honey and active substance Grayanotoxin III induced chromosome abnormalities in mice bone marrow cells(Elsevier Ireland Ltd, 2016) Muranlı, Fulya Dilek Gökalp; Rasgele, Pınar Göç; Kekeçoğlu, Meral; Kaya, Salih Tunç; Kambur, Merve…Öğe The role of ferroptotic cell death-related HMGB1 in inflammation crosstalk with cancer and myocardial Ischemia/reperfusion injury(Nova Science Publishers, Inc., 2022) Kaya, Salih Tunç; Güven, Celal; Taşkın, E.Inflammation is one of the critical defense pathways against pathogen and pathologic conditions, including cancer and myocardial ischemia/ reperfusion (MIR) injury. Therefore, inflammation has positive and negative impacts on tissues and organs. There are two types of inflammation, named as acute and chronic inflammation. The inflammation is also involved in the development of cancer and myocardial infarction. Damage-associated molecular patterns (DAMPs), such as High Mobility Group Box-1 (HMGB1), heat shock proteins (HSPs), ATP, and S100 proteins, are conservative danger molecules released from damaged or dying cells to trigger an immune response. However, they have essential roles in pathological inflammation to participate in self-defense in physiological and pathological circumstances. Recent evidence has emerged that inflammation may be a significant factor in the development and/or progression of cancer and myocardial infarction. Herein, we review current research on the role of HMGB1 in cancer and myocardial ischemia/reperfusion injury, focusing on inflammation. Furthermore, we have discussed the role of the posttranslational modification of HMGB1 in both illnesses. In addition, we focus on a new cell death pathway named ferroptosis, which may be involved in the development of both cancer and MIR through inflammation by HMGB1. © 2023 by Nova Science Publishers, Inc. All rights reserved.Öğe The role of toll-like receptors in the protective effect of melatonin against doxorubicin-induced pancreatic beta cell toxicity(Pergamon-Elsevier Science Ltd, 2019) Taşkın, Eylem; Güven, Celal; Kaya, Salih Tunç; Şahin, Leyla; Kocahan, Sayad; Değirmencioğlu, Arife Zuhal; Sevgiler, YusufAims: Doxorubicin, an anticancer drug, has a toxic effect on many tissues such as heart, pancreas, liver, kidney, and testis. The aim of current study is to investigate whether melatonin would be protective in doxorubicin-induced beta (beta) cell toxicity via HMGB1/TLR2/TLR4/MAPK/NF-kappa B signaling pathway. Main methods: Human pancreatic beta cell (1.1B4) was used in the present study. Four experimental groups were created as control, melatonin (10 mu M), doxorubicin (2 mu M) and the combination of melatonin with doxorubicin. Following 24-h treatment, Mitogen-activated protein kinase (MAPKs), Toll like receptors (TLRs) including TLR2 and TLR4, pro-and anti-apoptotic protein expression levels were determined by western blotting. Total antioxidant (TAS), oxidant status (TOS) and oxidative stress index (OSI) of the cells as well as superoxide dismutase (SOD) levels were determined. Active caspase-8 activity was measured and TUNEL staining was performed to study apoptotic pathways. Mitochondrial membrane potential (MMP), some protein expressions and F-actin distribution were analyzed. Key findings: Doxorubicin caused to depolarize MMP, resulting in enhancing apoptosis by activation of caspase-8 via MAPKs/NF-kappa B pathway via elevation of TOS and decreasing TAS. Also, doxorubicin destroyed F-actin distribution and elevated TLR2 and some apoptotic proteins, including Bax. However, co-treatment of melatonin with doxorubicin could reverse depolarization of MMP and inhibition of apoptosis through MAPK/NF-kappa B signaling by decreasing TOS and increasing TAS. The co-treatment reversed the alternations of TLR2, TLR4, MAPKs and apoptotic protein expressions induced by doxorubicin. Significance: Melatonin could be a good candidate against pancreatic beta cell toxicity-induced by doxorubicin through TLR2/TLR4/MAPK/NF-kappa B pathways.Öğe Short-term diabetes decreases ischemia reperfusion-induced arrhythmia: the effect of alpha-2 blocker yohimbine and glibenclamide(Tubitak Scientific & Technical Research Council Turkey, 2016) Bozdoğan, Ömer; Kaya, Salih Tunç; Yaşar, Selçuk; Baş, Erçin Çağdaş; Özarslan, Oğulcan Talat; Ekşioğlu, Didem; Erim, FirdevsThis study examined the effect of yohimbine alone and in combination with glibenclamide on ischemia and reperfusion-induced arrhythmias in diabetes. Six minutes of ischemia were produced in 1-week diabetic rats by ligation of the left coronary artery, and 6 min of reperfusion were produced by releasing the artery. A dose of 5 mg/kg of yohimbine and glibenclamide was administered for 7 days prior to the coronary ligation. The blood pressure, heart rate, and arrhythmia were determined from the recorded ECG during the 6 min of ischemia and reperfusion and then compared using a one-way ANOVA statistical program and the chi-square test. The score of arrhythmia calculated from the type and duration of arrhythmia decreased in the diabetic rats (3.5 +/- 1.69 in control, 1.7 +/- 0.81 in diabetes group). The arrhythmia score returned to the control value in the rats that were given a combination of yohimbine and glibenclamide (3 +/- 1.73). Yohimbine is used in the treatment of erectile dysfunction; glibenclamide is used as an antidiabetic drug in diabetic patients and may be a risk factor in the increase of ischemia reperfusion-induced arrhythmias.Öğe Silencing HMGB1 expression inhibits adriamycin's heart toxicity via TLR4 dependent manner through MAPK signal transduction(Imprimatur Publications, 2020) Taşkın, Eylem; Güven, Celal; Kaya, Salih Tunç; Sarıman, Melda; Emrence, Zeliha; Ekmekci, Sema Sırma; Akçakaya, HandanPurpose: Adriamycin (APR) is a commonly used anti-cancer drug. ADR has toxic effects on cardiomyocytes and leads to heart failure. However, the underlying mechanism(s) by which ADR causes heart failure is still not clarified exactly. The aim of present study is to investigate whether ADR-induced heart failure is mediated via HMGB1/TLR4 to initiate the apoptosis through MAPK/AMPK pathways. Methods: H9c2 cell line was used to create four groups as a control, HMGB1 inhibition, ADR, ADR+HMGB1 inhibition. Silencing HMGB1 was performed with specific small interfering RNA. ADR was used at 2 mu M concentration for 36 and 48 hours. Protein and genes expressions, apoptosis was measured. Results: Although ADR decreased AMPK, pAMPK, ERK1/2, pERK1/2, p38, JNK protein expression, ADR+HMGB1 inhibition led to change those protein expressions. The effect of silencing of HMGB1 prevented apoptosis induced by ADR in the cells. HMGB1 caused changes a kind of posttranscriptional modification on the TLR4 receptor. This posttranscriptional modification of TLR4 receptor led to decreased AMPK protein level, but phosphorylated-AMPK. This alternation of AMPK protein caused enhancing of JNK protein, resulting from the decline of p38 and ERK protein levels. Eventually, JNK triggered apoptosis by a caspase-dependent pathway. The number of TUNEL positive and active caspase 8 cells at ADR was high, although HMGB1 silencing could decrease the cell numbers. Conclusions: Inhibition of HMGB1 might prevent the lose of the cardiac cell by inhibition of apoptotic pathway, therefore HMGB1 plays an essential role as amplifying on ADR toxicity on the heart by TLR4.
