Mehmet Cansev

Bursa Uludağ Üni̇versi̇tesi̇ · Department of Medical Pharmacology

Background Status Epilepticus (SE) leads to the development of epilepsy with the contribution of Endoplasmic Reticulum (ER) stress. Uridine, a pyrimidine nucleoside, has been shown to have neuroprotective and antiepileptogenic effects in animal models. This study aimed to determine whether uridine ameliorates ER stress and apoptosis following epile...

In the current study, a novel wound dressing material for an effective wound healing was developed by loading Uridine (URD), an endogenous compound known for its regenerative properties, into polycaprolactone (PCL) nanofibers. Initially, PCL nanofibers without URD were fabricated from different PCL solutions (7, 8, 10 and 11% w/w) by electrospinnin...

Objectives: This study aimed to compare the efficacy of royal jelly (RJ) and its major fatty acid 10-hydroxy-2-decenoic acid (10-HDA) on ischemic stroke-related pathologies using histological and molecular approaches. Methods: Male rats were subjected to middle cerebral artery occlusion (MCAo) to induce ischemic stroke and were supplemented dail...

Şizofreni pozitif, negatif ve bilişsel belirtiler ile seyreden kronik bir beyin hastalığıdır. Bilişsel belirtiler hastalığın prodromal döneminden itibaren gözlenebilmektedir. Bu çalışmanın amacı irkilme refleksininin ön uyaran aracılı inhibisyonu (ÖUAİ) ile oluşturulan deneysel şizofreni modelinde sıçanların bilişsel fonksiyonlarını ve hipokampal p...

Several purinergic receptors have been identified on platelets which are involved in hemostatic and thrombotic processes. The aim of the present study was to investigate the effects of uridine and its nucleotides on platelet aggregation and hemostasis in platelet-rich plasma (PRP) and whole blood. The effects of uridine, UMP, UDP, and UTP at differ...

Antenatal steroid administration to pregnant women at risk of prematurity provides pulmonary maturation in infants, while it has limited effects on incidence of bronchopulmonary dysplasia (BPD), the clinical expression of hyperoxia-induced lung injury (HILI). Cytidine-5′-diphosphate choline (CDP-choline) was shown to alleviate HILI when administere...

Rapid eye movement (REM) sleep is associated with synaptic plasticity which is considered essential for long-term potentiation (LTP). The composition of extracellular matrix (ECM), in part, plays a role in REM sleep-associated synaptic functioning. The objective of this study was to investigate the effects of uridine administration on levels of mat...

Objectives: Sleep has a pivotal role in learning-memory and sleep deprivation (SD) negatively affects synaptic functioning. Cytidine-5-diphosphocholine (Citicoline) has been known to improve learning and memory functions. Our objective was to explore the effects of Citicoline on hippocampal and cortical synaptic proteins in rapid eye movement (REM...

Aim: Peripheral nerve regeneration remains an issue, and novel therapeutic approaches are required for functional recovery. This study investigated 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...

Endotoxin 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 CDP-choline on endotoxin...

Nasal secretory fluid proteomes (NSPs) can provide valuable information about the physiopathology and prognosis of respiratory tract diseases. This study aimed to determine changes in NSP by using proteomics in calves treated with lipopolysaccharide (LPS) or LPS + choline. Healthy calves (n = 10) were treated with LPS (2 µg/kg/iv). Five minutes aft...

This 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 f...

Botulism 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 a...

Aim: To investigate the anti-apoptotic and anti-oxidant effects of systemic uridine administration in a rat model of sciatic nerve injury. Material and methods: Thirty-two adult male rats were randomized equally to Sham, Control, U100 and U500 groups. Sham rats received a sham operation by exposing right sciatic nerve without transection, while...

Background/aim: Premature birth is a major problem that results in increased risk of mortality and morbidity. 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 uridin...

Cytidine 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 pla...

Background 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 o...

Endotoxemia treatment options are still of interest due to high mortality and choline treatment is one of them because of its role in the cholinergic anti-inflammatory pathway. This study investigated serum choline and butyrylcholinesterase (BChE) responses, and their correlations with inflammatory, oxidative stress and tissue damage biomarkers, in...

In recent years, an increasing number of research papers revealed that the compositional and volumetric alterations in the extracellular matrix are the consequences of aging and may be related to Alzheimer’s disease (AD). In this study, we aimed to demonstrate the alterations in hippocampal extracellular fluid proteins in vivo using the 5XFAD mouse...

Exposure to excessive oxygen in survivors of preterm birth is one of the factors that underlie the adverse neurological outcome in later life. Various pathological changes including enhanced apoptotic activity, oxidative stress and inflammation as well as decreased neuronal survival has been demonstrated in animal models of neonatal hyperoxia. The...

Chronic consumption of a diet enriched with nutritional precursors of phospholipids, including uridine and the polyunsaturated fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), was shown previously to enhance levels of brain phospholipids and synaptic proteins in rodents. Vitamin C, vitamin E, and selenium may directly affec...

Background / Aim: Recent studies revealed that the brain extracellular matrix (ECM) molecules have several roles on the synaptic response and the stabilization of synaptic connectivity in Alzheimer’s Disease (AD). In order to investigate the role of ECM in the genesis and progression of the disease, we analyzed the proteome alterations in the hippo...

Hypoxic-ischemic encephalopathy (HIE), is the most common brain disorder in neonates during the perinatal period, which, to date, can only be managed to some extent by hypothermia. Uridine is the principal circulating pyrimidine in humans which is utilized as a precursor for membrane phospholipid biosynthesis. Uridine has recently been shown to pro...

The aim of the present study was to investigate effects of intravenous (i.v.) choline treatment on serum matrix metalloproteinases (MMP), MMP tissue inhibitors (TIMP) and immunoglobulins (Igs), and to determine if there were relations between serum MMPs/TIMPs and C-reactive protein (CRP) (as a marker of the acute phase response), immunoglobulin G a...

Background This study aimed to investigate the possible serum protein changes after endotoxin administration in healthy and choline-treated calves using proteomics. These results are expected to contribute to the understanding of the pathophysiological mechanisms of endotoxemia and the beneficial effect of choline administration in this clinical si...

Statement of significance: Biomimetic nanomaterials bearing natural bioactive signals which are derived from extracellular matrix components like laminin and heparan sulfates provide promising therapeutic strategies for regeneration of the nervous system. However, no research has been reported exploring the use of biomimetic materials against dege...

Phospholipids are the main constituents of brain membranes. Formation of new membranes requires that uridine, the omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA), and choline, the three circulating precursors of major phospholipids, interact via the Kennedy pathway. Supplementation of laboratory rodents with uridine, DHA and...

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Crude lecithin, a mixture of mainly phospholipids, potentially helps to increase the systemic availability of dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), such as docosahexaenoic acid (DHA). Nevertheless, no clear data exist on the effects of prolonged combined dietary supplementation of DHA and lecithin on RBC and plasma PUFA levels. In...

Objective: Histone acetylation and deacetylation may play a role in the pathogenesis of inflammatory lung diseases. We evaluated the preventive effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on neonatal hyperoxic lung injury. Methods: Forty newborn rat pups were randomized in normoxia, normoxia+VPA, hyperoxia and hyperoxi...

Fortasyn Connect (FC) is a specific nutrient combination designed to target synaptic dysfunction in Alzheimer’s disease by providing neuronal membrane precursors and other supportive nutrients. The aim of the present study was to investigate the effects of FC on hippocampal cholinergic neurotransmission in association with its effects on synaptic m...

Thioflavin T and AT8 antibody staining. Results: Resveratrol reduced the level of aggregated phosphorylated tau by 73% as judged by the mean AT8 immunoreactive area (p¼0.017), while the 35% reduction by morin did not reach significance (Figure, p¼0.14). Neither resveratrol nor morin affected motor function. Conclusions: Oral treatment with re-svera...

The aim of this study was to investigate the dose dependence of citicoline's previously-reported effects on recovery of peripheral nerve injury. MATERIAL and Right sciatic nerves of sixty adult female Wistar Albino rats were incised and primary anastomosis was performed. Rats were then divided into four groups: Control group received 2 ml of saline...

Background: Choline is an important component of human breast milk and its content varies considerably among breastfeeding women and lactation periods. Objective: The aim of this study was to assess the relationship between breast milk choline contents and inflammatory status in breastfeeding women. Methods: Breast milk choline compounds and s...

Background: Bronchopulmonary dysplasia (BPD) is an important cause of morbidity. The aim of this study was to evaluate the preventive effect of cytidine 5'-diphosphocholine (CDP-choline) treatment on hyperoxic lung injury in a neonatal rat model. Methods: A total of 30 newborn pups were divided into control, hyperoxia, and hyperoxia + CDP-cholin...

The purpose of this study was to investigate the effects of parenteral uridine administration on acetylcholine release by in vivo microdialysis in striatum of freely‐moving rats. Microdialysis probes inserted into left striatum of rats were perfused with artificial cerebrospinal fluid. After collection of 3 basal microdialysate samples, uridine was...

Life-threatening diseases like sepsis/endotoxemia commonly result with death despite comprehensive treatment modalities. Studies are underway regarding understanding the complex pathophysiological mechanism of sepsis, describing criteria for early diagnosis and developing new treatment approaches in order to decrease mortality.

Background: Cytidine 5'-diphosphocholine (CDP-choline) is an endogenous intermediate in the biosynthesis of phosphatidylcholine, a contributor to the mucosal defense of the intestine. The aim of this study was to evaluate the possible cytoprotective effect of CDP-choline treatment on intestinal cell damage, membrane phospholipid content, inflammat...

Purpose The purpose of this study was to evaluate the preventive effect of CDP-choline treatment on hyperoxic lung injury, inflammation and apoptosis in a neonatal rat model of bronchopulmonary dysplasia BPD. Methods A total of 30 newborn pups were arranged in control, hyperoxia, and hyperoxia+CDP-choline groups. Immediately after birth, pups in th...

Methods A total of 30 rat pups (0 days old) were divided equally into 3 groups: control, hyperoxia and hyperoxia+VPA groups. In hyperoxia groups, pups were maintained in 95% O2 for 10 days while control group was maintained in room air. VPA was administered intraperitoneally once daily for the first 10 days of life. On day 10, histopathological sco...

Background The aim of this study was to evaluate the possible cytoprotective effect of CDP-choline treatment on intestinal cell death and apoptosis in a neonatal rat model of NEC. Methods A total of 30 newborn pups were divided equally into 3 groups as follows: Control, NEC, and NEC+CDP-choline groups. NEC was induced by enteral formula feeding, ex...

Introduction Neurodegenerative diseases were associated with a decrease in histone acetylase transferase (HAT) activity, resulting in relative over-deacetylation. Histone deacetylase (HDAC) inhibitors were suggested as potentially neuroprotective agents. The aim of this sudy was to evaluate the neuroprotective effects of valproic acid (VPA), an his...

The objective of this study was to investigate the effect of citicoline administration on epidural fibrosis which is a frequent complication of lumbar disc surgery with no effective treatment or preventive surgical technique. MATERIAL and Sixty Sprague-Dawley female rats undergoing L4-5 right hemilaminotomy and annular fenestration were arranged in...

Topical cytidine-5'-diphosphocholine (CDP-choline) improves functional recovery and promotes nerve regeneration in sciatic nerve injury in rats. The aims of this study were to test whether systemic treatment with CDP-choline was effective in improving the recovery of injured sciatic nerve, and to determine whether the cytidine and/or choline moieti...

Butyrylcholinesterase (BChE) and paraoxonase 1 (PON1) are two serum enzymes synthesized by the liver that are related with inflammation. The main objectives of this study were to determine changes in serum BChE and PON1 by using a canine model of endotoxemia, and to evaluate whether choline alters BChE and PON1 activities during inflammation. For t...

This study investigated the effects of hypoxic and hyperosmotic stresses on the matrix metalloproteinases 2 and 9 (MMP-2, MMP-9) and their tissue inhibitors 2 and 1 (TIMP-2, TIMP-1) respectively in cultured lung fibroblasts from broiler chickens. Isolated and sub-cultured primary lung fibroblasts from 1-day-old broilers were exposed to hypoxia and...

Chronic oral administration of various membrane phosphatide precursors (e.g., cytidine, uridine, polyunsaturated fatty acids, and choline) enhances learning and memory and improves diminished cognitive performance in experimental animals. In addition, treatment with a mixture containing the phosphatide precursors uridine, docosahexaenoic acid (DHA)...

Brain phosphatide synthesis requires three circulating compounds: docosahexaenoic acid (DHA), uridine, and choline. Oral administration of these phosphatide precursors to experimental animals increases the levels of phosphatides and synaptic proteins in the brain and per brain cell as well as the numbers of dendritic spines on hippocampal neurons....

Sepsis/endotoxemia causes platelet dysfunctions, abnormalities in coagulation and hemostatic mechanisms leading to organ dysfunctions and mortality. Choline prevents organ injury and improves survival during endotoxemia. The main objective of the present study was to determine the effects of choline or cytidine-5'-diphosphocholine (CDP-choline) on...

Choline, a quaternary amine obtained largely from the diet but also synthesized in the brain and, especially, liver, is an essential precursor of the neurotransmitter acetylcholine (ACh) and of the major membrane constituent phosphatidylcholine (PC). Plasma choline concentrations can vary over a fivefold range depending on the choline contents of t...

We showed previously that choline administration protects dogs from endotoxin-induced multiple organ injury and platelet dysfunctions. Since sepsis/endotoxemia is associated with alterations in lipid metabolism, we have investigated whether choline or cytidine-5'- diphosphocholine (CDP-choline), a choline donor, alters serum lipid responses to endo...

New brain synapses form when a postsynaptic structure, the dendritic spine, interacts with a presynaptic terminal. Brain synapses and dendritic spines, membrane-rich structures, are depleted in Alzheimer's disease, as are some circulating compounds needed for synthesizing phosphatides, the major constituents of synaptic membranes. Animals given thr...

Objective The loss of cortical and hippocampal synapses is a universal hallmark of Alzheimer’s disease, and probably underlies its effects on cognition. Synapses are formed from the interaction of neurites projecting from “presynaptic” neurons with dendritic spines projecting from “postsynaptic” neurons. Both of these structures are vulnerable to t...

Developing neurons synthesize substantial quantities of membrane phospholipids in producing new synapses. We investigated the effects of maternal uridine (as uridine-5'-monophosphate) and docosahexaenoic acid supplementation on pups' brain phospholipids, synaptic proteins and dendritic spine densities. Dams consumed neither, 1 or both compounds for...

Administering uridine-5′-monophosphate (UMP) and docosahexaenoic acid (DHA) increases synaptic membranes (as characterized by pre- and post-synaptic proteins) and dendritic spines in rodents. We examined their effects on rotational behavior and dopaminergic markers in rats with partial unilateral 6-hydroxydopamine (6-OHDA)-induced striatal lesions....

Central administration of choline increases blood pressure in normotensive and hypotensive states by increasing plasma concentrations of vasopressin and catecholamines. We hypothesized that choline could also modulate the renin–angiotensin pathway, the third main pressor system in the body. Plasma renin activity (PRA), which serves as an index of t...

The present study was designed to test the effects of choline, cytidine-5'-diphosphocholine (CDP-choline) and phosphocholine on plasma glucagon concentrations in rats. Intraperitoneal (i.p.) injection of 200-600 micromol/kg of choline, CDP-choline or phosphocholine produced a dose-dependent increase in plasma glucagon and choline concentrations. Pr...

1 Intraperitoneal (i.p.) injection of 200–600 μmol/kg of cytidine‐5′‐diphosphocholine (CDP‐choline) increased plasma adrenaline and noradrenaline concentrations dose‐ and time‐dependently. 2 CDP‐choline treatment caused several‐fold increases in plasma concentrations of CDP‐choline and its metabolites phosphocholine, choline, cytidine monophosphate...

The present study was designed to test the effects of CDP-choline and its metabolites on serum insulin concentrations in rats and to investigate the involvements of cholinergic and adrenergic receptors in the effect. Intraperitoneal (i.p.) administration of CDP-choline (200-600 micromol/kg) increased serum insulin in a dose- and time-related manner...

Although cognitive performance in humans and experimental animals can be improved by administering omega-3 fatty acid docosahexaenoic acid (DHA), the neurochemical mechanisms underlying this effect remain uncertain. In general, nutrients or drugs that modify brain function or behavior do so by affecting synaptic transmission, usually by changing th...

Intraperitoneal administration of CDP-choline (200-900 μmol/kg) increased blood pressure and decreased heart rate of rats in a dose- and time-dependent manner. These responses were accompanied by elevated serum concentrations of CDP-choline and its metabolites phosphocholine, choline, cytidine monophosphate and cytidine. Blood pressure increased by...

The uridine nucleotides UTP, UDP and UDP-sugars produce a variety of effects by activating specific G protein- coupled P2Y receptors, i.e., the P2Y2, P2Y4, P2Y6 and P2Y14 variants. Except for P2Y14 which has recently been defined, stimulation of P2Y receptors by UTP and/or UDP augments proliferation of adult multipotent neural stem cells; stimulate...

Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, is an essential component of membrane phosphatides and has been implicated in cognitive functions. Low levels of circulating or brain DHA are associated with various neurocognitive disorders including Alzheimer's disease (AD), while laboratory animals, including animal models of AD,...

CDP-choline is an endogenous metabolite in phosphatidylcholine biosynthesis. Exogenous administration of CDP-choline has been shown to affect brain metabolism and to exhibit neuroprotective actions. On the other hand, little is known regarding its peripheral actions. Intraperitoneal administration of CDP-choline (200-600 micromol/kg) induced a dose...