Person: CANSEV, MEHMET
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CANSEV
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MEHMET
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Publication Anti-apoptotic and anti-oxidant effects of systemic uridine treatment in an experimental model of sciatic nerve injury(Türk Nöroloji Derneği, 2021-01-01) Khezri, Marzieh Karimi; Turkkan, Alper; Khezri, Marzieh Karimi; Koç, Cansu; KOÇ, CANSU; Salman, Berna; SALMAN, BERNA; Levent, Pinar; Cakir, Aysen; Kafa, Ilker Mustafa; Cansev, Mehmet; Bekar, Ahmet; ÇAKIR, AYŞEN; KAFA, İLKER MUSTAFA; CANSEV, MEHMET; BEKAR, AHMET; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Anatomi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0002-6097-5585; 0000-0001-8309-0934; 0000-0003-2918-5064; AAA-4754-2022; ABX-9081-2022; A-6819-2018AIM: To investigate the anti-apoptotic and anti-oxidant effects of systemic uridine treatment in a rat model of sciatic nerve injury.MATERIAL and METHODS: Thirty-two adult male rats were equally randomized to Sham, Control, U100, and U500 groups. Sham rats received a sham operation by exposing the right sciatic nerve without transection, while those in the Control, U100, and U500 groups underwent right sciatic nerve transection followed by immediate primary anostomosis. Sham and Control groups received saline (0.9% NaCl) injections intraperitoneally (i.p.), while U100 and U500 groups received 100 mg/kg and 500 mg/kg uridine injections (i.p.), respectively, once a day for 7 days after the surgery. Rats in all the groups were sacrificed on the eighth day; sciatic nerve samples were analyzed for apoptosis by Western Blotting and for oxidation parameters including myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) by Enzyme-Linked Immunosorbent Assay (ELISA).RESULTS: Uridine treatment at the dose of 500 mg/kg significantly decreased as apoptosis determined by Caspase-3/Actin ratio and exhibited significant anti-oxidant effects as determined by decreased levels of MPO and MDA as well as increased levels of SOD, GPx, and CAT compared to controls. Uridine at 100 mg/kg was only found to decrease the Caspase-3/Actin ratio, although it significantly decreased MDA and increased CAT levels compared to controls.CONCLUSION: Treatment with uridine reduces apoptosis and oxidation in a rat model of sciatic nerve injury dose-dependently. Thus, uridine may be beneficial in peripheral nerve regeneration by exhibiting anti-apoptotic and anti-oxidant effects.Publication Antioxidative effects of uridine in a neonatal rat model of hyperoxic brain injury(TÜBİTAK, 2020-05-31) Al, Nevin; Çakir, Aysen; Koç, Cansu; Cansev, Mehmet; Alkan, Tülin; ÇAKIR, AYŞEN; KOÇ, CANSU; CANSEV, MEHMET; ALKAN, TÜLİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; 0000-0002-6097-5585; 0000-0003-2918-5064; 0000-0001-6466-5042; AAA-4754-2022; A-6819-2018; M-9071-2019; AAH-1792-2021Background/aim: Premature birth is a major problem that results in an increased risk of mortality and morbidity. The management of such infants consists of supraphysiological oxygen therapy, which affects brain development due, in part, to the deterioration caused by reactive oxygen species (ROS). We showed previously that exogenously administered uridine provides neuroprotection in a neonatal rat model of hyperoxic brain injury. Hence, the aim of the present study was to investigate the effects of uridine on ROS in the same setting.Materials and methods: Hyperoxic brain injury was induced by subjecting a total of 53 six-day-old rat pups to 80% oxygen (the hyperoxia group) for a period of 48 h. The pups in the normoxia group continued breathing room air (21% oxygen). Normoxia + saline or hyperoxia + saline or hyperoxia + uridine 100 mg/kg or hyperoxia + uridine 300 mg/kg or hyperoxia + uridine 500 mg/kg was injected intraperitoneally (i. p.) 15 min prior to the hyperoxia procedure. The pups were decapitated and the brains were homogenized to analyze superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), and malondialdehyde (MDA) enzymes as well as DJ-1 (protein deglycase DJ-1) - an oxidative stress-sensitive protein.Results: Hyperoxia-induced may cause overproduction of oxygen radicals and the oxidant/antioxidant balance may be disturbed in the brain. Brain MPO and MDA levels were significantly increased in saline-receiving pups exposed to hyperoxia. Brain SOD and GSH-Px levels were significantly decreased in saline-receiving pups exposed to hyperoxia. Our results showed that uridine administration prevented the hyperoxia-induced decrease in SOD and GSH-Px while counteracting the hyperoxia-induced increase in MPO and MDA in a dose-dependent manner. Uridine also increased the DJ-1 levels in brains of rat pups subjected to hyperoxia.Conclusion: These data suggest that uridine exhibits antioxidative properties which may mediate the protective effects of uridine in a neonatal rat model of hyperoxic brain injury.Publication Evaluation of serum choline along with, some biochemical and clinical parameters in cattle suffering from with botulism(Pakistan Agricultural Scientists Forum, 2021-02-01) Batmaz, Hasan; Mecitoğlu, Zafer; Koç, Cansu; Kaya, Fatih; Topal, Onur; Cansev, Mehmet; BATMAZ, HASAN; MECİTOĞLU, ZAFER; KOÇ, CANSU; KAYA, FATİH; TOPAL, ONUR; CANSEV, MEHMET; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/İç Hastalıkları Anabilim Dalı; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı; 0000-0002-6097-5585; 0000-0001-8820-1509; 0000-0002-1933-7354; 0000-0003-2918-5064; M-9071-2019; AAA-4754-2022; IXN-7700-2023; S-8278-2017; HXD-1722-2023; FQB-3477-2022Botulism is a disease of cattle that causes significant impact due to its high mortality rate. The aim of the present study is to evaluate serum choline levels as well as clinical and biochemical parameters of cattle suspected to be suffering from botulism and to compare the results with healthy cattle and also to compare the results of survivors and fatalities. Thirteen botulism suspected and eleven healthy cattle were used. Total protein, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), calcium, phosphorus, magnesium and potassium levels were measured from the sera of botulism and control cattle by colorimetric method using an autoanalyser. Choline levels were analyzed using HPLC. Dysphagia, decreased tongue strength weak anal reflexes, tongue and tail paralysis and locomotion disorders were the main clinical findings observed in suspected botulism cases. Botulinum toxin analysis of ruminal fluid samples were positive in two cattle from one herd. AST, ALT, potassium and choline levels were higher in cattle suffering from suspected botulism cases and choline levels were positively correlated with albumin and total protein levels. Three animals from botulism group survived. Clinical findings were milder, animals were not recumbent and choline levels were lower in survivors. Clinical findings of the three animals that recovered were milder, animals were not recumbent and choline levels were lower in survivors. It was observed that clinical findings such as decreased tongue strength and anal reflexes, dysphagia, tail paralysis, and locomotion disorders are important for diagnosis of botulism In conclusion, cattle with milder clinical signs and lower choline have a higher chance of survival.Publication Choline or cdp-choline restores hypotension and improves myocardial and respiratory functions in dogs with experimentally-induced endotoxic shock(Elsevier, 2021-10-27) Ozarda, Yesim; Ceron, Jose Joaquin; Buturak, Ali; Ulus, Ismail H.; Kocaturk, Meric; KOCATÜRK, MERİÇ; Yilmaz, Zeki; YILMAZ, ZEKİ; Cansev, Mehmet; CANSEV, MEHMET; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Veteriner Fakültesi.; 0000-0002-2849-1222; 0000-0001-9836-0749; 0000-0003-2918-5064; 0000-0002-8654-1793; H-9043-2015; D-5340-2015; V-5578-2017; A-9637-2008Endotoxin shock is associated with severe impairments in cardiovascular and respiratory functions. We showed previously that choline or cytidine-5 '-diphosphocholine (CDP-choline) provides beneficial effects in experimental endotoxin shock in dogs. The objective of the present study was to determine the effects of choline or CDPcholine on endotoxin-induced cardiovascular and respiratory dysfunctions. Dogs were treated intravenously (i.v.) with saline or endotoxin (LPS, 0.1 mg/kg) 5 min before i.v. infusion of saline, choline (20 mg/kg) or CDP-choline (70 mg/kg). Blood pressure, cardiac rate, myocardial and left ventricular functions, respiratory rate, blood gases, serum electrolytes and cardiac injury markers were determined before and at 0.5-48 h after endotoxin. Plasma tumor necrosis factor alpha (TNF-alpha), high mobility group box-1 (HMGB1), catecholamine and nitric oxide (NO) levels were measured 2 h and 24 h after the treatments. Endotoxin caused immediate and sustained reductions in blood pressure, cardiac output, pO2 and pH; changes in left ventricular functions, structure and volume parameters; and elevations in heart rate, respiratory rate, pCO2 and serum electrolytes (Na, K, Cl, Ca and P). Endotoxin also resulted in elevations in blood levels of cardiac injury markers, TNF-alpha, HMGB1, catecholamine and NO. In choline- or CDP-choline-treated dogs, all endotoxin effects were much smaller in magnitude and shorter in duration than observed values in controls. These data show that treatment with choline or CDP-choline improves functions of cardiovascular and respiratory systems in experimental endotoxemia and suggest that they may be useful in treatment of endotoxin shock in clinical setting.Publication Effects of cdp-choline administration on learning and memory in rem sleep-deprived rats(Pergamon-elsevier Science Ltd, 2020-01-01) Çakır, Aysen; Öcalan, Busra; Suyen, Guldal Güleç; Kahveci, Nevzat; Koç, Cansu; KOÇ, CANSU; Cansev, Mehmet; CANSEV, MEHMET; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; 0000-0002-6097-5585; 0000-0003-2918-5064; AAA-4754-2022; AAL-1786-2020; M-9071-2019Cytidine 5-diphosphocholine (CDP-choline) administration has been shown to improve learning and memory deficits in different models of brain disorders. In this study, effects of CDP-choline on the well known negative effects of Rapid Eye Movements (REM) sleep deprivation on learning and memory were investigated. Sleep deprivation was induced by placing adult male Wistar albino rats on 6.5 cm diameter platforms individually for 96 h according to flower pot method. Learning and memory performances were evaluated using Morris Water Maze (MWM) test during the same period of time. Saline or CDP-choline (100 mu mol/kg, 300 mu mol/kg or 600 mu mol/kg) was administered intraperitoneally 30 min prior to the onset of MWM experiments. On completion of behavioral tests, rats were decapitated and hippocampi were assayed for total and phosphorylated Ca2+/calmodulin-dependent protein kinase II (tCaMKII and pCaMKII, respectively) and total antioxidant capacity. We observed that while REM sleep deprivation had no effect on learning, it diminished the memory function, which was associated with decreased levels of pCaMKII and total antioxidant capacity in the hippocampus. CDP-choline treatment blocked the impairment in memory function of sleep-deprived rats and, increased pCaMKII levels and total antioxidant capacity. These data suggest that CDP-choline reduces REM sleep deprivation-induced impairment in memory, at least in part, by counteracting the disturbances in biochemical and molecular biological parameters.Publication Changes in choline and cholinesterase in saliva of dogs with parvovirus infection(Elsevier, 2021-01-01) Kocatürk, Meriç; Tecles, Fernando; Yalçın, Ebru; Cihan, Hüseyin; Tural, Merve; Levent, Pınar; Cansev, Mehmet; Ceron, Jose J.; Yılmaz, Zeki; KOCATÜRK, MERİÇ; YALÇIN, EBRU; CİHAN, HÜSEYİN; Tural, Merve; Levent, Pınar; CANSEV, MEHMET; YILMAZ, ZEKİ; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/İç Hastalıkları Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; 0000-0002-2849-1222; 0000-0001-6703-4908; 0000-0003-2918-5064; 0000-0001-9836-0749; M-9071-2019; GDR-9018-2022 ; V-5578-2017; ACP-9956-2022; A-9637-2008; ABH-3742-2020; DDR-1481-2022This study investigated the changes in choline (Ch) and butyrylcholinesterase (BChE) in saliva in canine parvovirosis (CP) as a model of sepsis, and their correlations with these analytes in serum and with other markers of inflammation such as white blood cell count (WBC) and serum C-reactive protein (CRP). A total of 30 dogs with CP were sampled for saliva and serum at presentation, and 10 healthy puppies were also sampled as controls. Salivary Ch was higher in dogs with CP (P < 0.001) showing a positive correlation with CRP, whereas no differences were observed in salivary BChE. This is the first report in which Ch is measured in saliva of dogs and based in the results of this study, salivary Ch could be potentially used as biomarker of the severity of CP.Publication Proteomics analysis of CA1 region of the hippocampus in pre-, progression and pathological stages in a mouse model of the alzheimer's disease(Bentham Science, 2019-01-01) Gürel, Buşra; Cansev, Mehmet; Koç, Cansu; Öçalan, Buşra; Çakır, Ayşen; Aydın, Samı; Kahveci, Nevzat; Ulus, İsmail Hakkı; Şahin, Betül; Başar, Merve Karayel; Baykal, Ahmct Tarık; CANSEV, MEHMET; KOÇ, CANSU; Öçalan, Buşra; ÇAKIR, AYŞEN; Aydın, Sami; KAHVECİ, NEVZAT; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Bilim Dalı; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Bilim Dalı; 0000-0002-6097-5585; 0000-0003-0841-8201; 0000-0002-3405-3640; 0000-0001-7729-7373; AAG-7070-2021; AAA-4754-2022; A-6819-2018; AAL-1786-2020; M-9071-2019; N-9927-2019; CCT-7508-2022Background: CA1 subregion of the hippocampal formation is one of the primarily affected structures in AD, yet not much is known about proteome alterations in the extracellular milieu of this region. Objective: In this study, we aimed to identify the protein expression alterations throughout the pre-pathological, progression and pathological stages of AD mouse model.Methods: The CA1 region perfusates were collected by in-vivo intracerebral push-pull perfusion from transgenic 5XFAD mice and their non-transgenic littermates at 3, 6 and 12 were beta months of age. Morris water maze test and immunohistochemistry staining of A performed to determine the stages of the disease in this mouse model. The protein expression differences were analyzed by label-free shotgun proteomics analysis.Results: A total of 251, 213 and 238 proteins were identified in samples obtained from CA1 regions of mice at 3, 6 and 12 months of age, respectively. Of these, 68, 41 and 33 proteins showed statistical significance. Pathway analysis based on the unique and common proteins within the groups revealed that several pathways are dysregulated during different stages of AD. The alterations in glucose and lipid metabolisms respectively in pre-pathologic and progression stages of the disease, lead to imbalances in ROS production via diminished SOD level and impairment of neuronal integrity.Conclusion: We conclude that CA1 region-specific proteomic analysis of hippocampal degeneration may be useful in identifying the earliest as well as progressional changes that are associated with Alzheimer's disease.Publication In vivo protective effect of Uridine, a pyrimidine nucleoside, on genotoxicity induced by Levodopa/Carbidopa in mice(Pergamon-Elsevier, 2015-08-01) Yaylagül, Esra Örenlili; Cansev, Mehmet; Kasımoğullari, Serap Çelikler; CANSEV, MEHMET; ÇELİKLER KASIMOĞULLARI, SERAP; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0003-2918-5064; M-9071-2019; JCP-8028-2023Parkinson's disease (PD) is a common neurodegenerative disorder that affects millions of people all over the world. Motor symptoms of PD are most commonly controlled by L-3,4-dihydroxyphenylalanine (Levodopa, L-DOPA), a precursor of dopamine, plus a peripherally-acting aromatic-L-amino-acid decarboxylase (dopa decarboxylase) inhibitor, such as carbidopa. However, chronic treatment with a combination of Levodopa plus carbidopa has been demonstrated to cause a major complication, namely abnormal involuntary movements. On the other hand, the effect of this treatment on bone marrow cells is unknown. Therefore, in this study, we aimed to investigate possible genotoxic effects of Levodopa and Carbidopa using male Balb/C mice. Our results showed that Levodopa alone or in combination with carbidopa caused genotoxicity in in vivo micronucleus test (mouse bone marrow) and Comet assay (blood cells). Furthermore, we showed that simultaneous administration of uridine, a pyrimidine nucleoside, reversed the genotoxic effect of Levodopa and Carbidopa in both assays. Our data show for the first time that Levodopa plus carbidopa combination causes genotoxicity which is reversed by uridine treatment. These findings might enhance our understanding for the complications of a common Parkinson's treatment and confer benefit in terms of reducing a possible genotoxic effect of this treatment.Publication Uridine treatment improves nerve regeneration and functional recovery in a rat model of sciatic nerve injury(Turkish Neurosurgical Soc, 2022-01-01) Khezri, Marzieh Karimi; Türkkan, Alper; KOÇ, CANSU; Salman, Berna; SALMAN, BERNA; Levent, Pınar; Çakır, Aysen; ÇAKIR, AYŞEN; CANSEV, MEHMET; KAFA, İLKER MUSTAFA; Bekar, Ahmet; BEKAR, AHMET; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Anatomi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmaoloji Anabilim Dalı.; 0000-0002-6097-5585; 0000-0001-8309-0934; 0000-0003-2918-5064; A-6819-2018; ABX-9081-2022AIM: To investigate the regenerative potential and long-term functional effects of uridine treatment in a rat model of sciatic nerve injury.MATERIAL and METHODS: Male Sprague-Dawley rats were randomized to receive sham surgery plus saline (Sham group), right sciatic nerve transection and primary repair plus saline (Control group), right sciatic nerve transection, and primary repair plus 500 mg/kg uridine (Uridine group). Saline or uridine was injected intraperitoneally (i.p.) for seven days, and the rats were monitored for 12 weeks after surgery. We evaluated electrophysiological and functional recovery using electromyography (EMG) and sciatic functional index (SFI) at six and 12 weeks, respectively. At 12 weeks, rats were decapitated and their right sciatic nerves were examined in macroscopic and histomorphologic manners.RESULTS: Functional evaluation by SFI and sciatic nerve conduction velocity analyzed by EMG both decreased in the Control group but recovered in the Uridine group 12 weeks after surgery. Additionally, upon experiment completion, Uridine treatment was observed to enhance nerve adherence, separability scores, and the number of myelinated axons.CONCLUSION: These results reveal that short-term Uridine treatment provides morphological and electrophysiological benefits, which are represented by long-term functional improvement in a rat model of sciatic nerve injury. These findings validate and extend our knowledge on Uridine's regenerative effects in peripheral nerve injuries.Publication Effects of short-term uridine treatment on blood-brain barrier integrity and brain edema in li-pilocarpine-induced status epilepticus(Wiley, 2023-01-01) Aydın, Birnur; Esmerce, Buşra Öcalan; ÇAKIR, AYŞEN; ESMERCE, BÜŞRA; KOÇ, CANSU; Koç, Cansu; Tuncak, Şüeda; TUNÇAK, SÜEDA; Cansev, Mehmet; CANSEV, MEHMET; Alkan, Tulin; ALKAN, TÜLİN; AAH-1792-2021; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; 0000-0002-8193-474X; 0000-0003-2918-5064; 0000-0001-6466-5042; LFV-6689-2024; M-9071-2019; A-6819-2018; AAH-1734-2021; AAH-1734-2021; A-6819-2018; LFV-6689-2024; AAH-1792-2021