Background: SODIUM arsenite (NaAsO2) is a common mineral contaminant in drinking water in numerous parts of the world. It has been shown to have cardiovascular, metabolic, neuroendocrine, and urinary effects on the body. There is abundant scientific evidence that establishes a strong correlation between arsenic exposure and kidney-related disorders. Objectives: The present study aimed to investigate the potential protective effect of CITICOLINE against NaAsO2-induced nephrotoxicity. Methods: The groups included a control group, a group treated with NaAsO2 at a concentration of 50 ppm, a group treated with Cit at a dosage of 1000 mg/kg, and three groups of NaAsO2 (50 ppm) co-treated with Cit at doses of 250, 500, and 1000 mg/kg, respectively. Results: CITICOLINE decreased the level of blood urea nitrogen (P < 0. 001), creatinine levels (P < 0. 001), thiobarbituric acid reactive substances (P < 0. 001), nitric oxide (P < 0. 001), inflammatory factors tumor necrosis factor-α (P < 0. 001) and interleukin-6 (P < 0. 001 and P < 0. 001). Furthermore, Cit increased total thiol (P < 0. 001) and activity levels of catalase (P < 0. 05 and P < 0. 001), superoxide dismutase (P < 0. 01 and P < 0. 001), and glutathione peroxidase (P < 0. 001). Therefore, Cit reduced the harmful effects caused by the imbalance in oxidative and antioxidant systems and histopathological damage in NaAsO2-intoxicated mice, improving the damage caused by oxidative stress and inflammation. Conclusions: Our research shows that Cit can protect the kidneys against the damaging effects of NaAsO2 by using its antioxidant and anti-inflammatory properties.

CITICOLINE (CDP-Choline) is an essential intermediate in the biosynthetic pathway of Phosphatidy1choline, and the later is a main component of neuronal membranes. Many experimental and few clinical studies showed the beneficial effect of CITICOLINE in cerebrovascular diseases, memory disturbances and cognitive disorders.The current trial was a case - control study in 60 (40 patients as the cases and 20 patients as controls) nondiabetic, 50-70 years old patients who had an ischemic stroke in the MCA territory for the first time. CITICOLINE (500 mg/day/IV or IM) was administered in the first 24h of stroke and continued for 4 weeks. Barthel Index measured the neurologic function of the patients in the first day, 4th week and eighth week.After 4 weeks patients in CITICOLINE group had significantly greater improvement of neurologic function (p=0/01). Patients with more severe disability (BI<45) had more improvement at the end of 4th and 8th week. (59,5 for CITICOLINE and 39,6 for control group (p=0.001). The percent of patients who had a full recovery (95) were greatly higher in CITICOLINE group at eighth week.This study suggests that CITICOLINE was effective in enhancing neuroligic recovery in stroke patients especially in a subgroup of patients who had more disability at the beginning.

CITICOLINE (CDP-choline;cytidine 5prime-diphosphocholine) is a form of the essential nutrient choline that shows promise of clinical efficacy in elderly patients with cognitive deficits, inefficient memory and early-stage Alzheimer’s disease. CITICOLINE has also been investigated as a therapy in stroke patients. It has been disclosed that prepared according to a chemically synthetic method, but it is difficult to produce it on a commercial scale. Thus it is important to providing a method for producing a purified CITICOLINE in a good yield at low cost and capable of implementation on an industrial scale is clear. In enzymatic method That applied in this research CITICOLINE is extracted of the Culture liquor that in this resaerch named Culture. The Culture filterated was passed through a column of strongly basic anion exchang resin. Then strongly basicanion Exechanger-quaternary ammonium type I 62096 Lewatit OC-1950 Styrene-DVB gel-type was washed with water and formic acid. This solution was passed through the column with gradual increase in the concentration of formic acid (until 0.04 N Max.). A fraction of CITICOLINE was collected by elution according to the so-called gradient elution method. In this research for extracted microorganism enzymatic system, they was treated with distilled water and sonication with 50-60Hz wave length, that result was shown this mwthod don’t have any effect on extracting the enzymatic system. But added aceton cause lossing the yeast cell wall and follow it adding Sorfactant extracted it and formed citicolin in the culter. forming investigated by TLC (Thin Layer Chromatography) method. Results was shown that citicolin was formed 3 to 4 hours after the culturing. and adding surfactant to the culture liquer increase the forming of CITICOLINE that should be investigate. For assaying citicholin that was formed in the liquer HPLC method used. In purification that carried out with column of strongly basic anion exchang resin with 1ml/3min/sq. cm rate was showed that max. of CITICOLINE can exist in 450 min from column. The results showed that with this method 1. 338mg/ml. citicholin formed and addind the sorfactant increasing it to 1.41md/ml.Preparing CITICOLINE by this method is usable and we can apply it in the industrial level But it is necessary more research for increasing its output.

Thiopental SODIUM is an ultra short-acting barbiturate. Due to its redistribution characteristic, its first injection has a short term effect. In order to elongate its anesthesia duration, more injections are needed. As these additional injections extend the recovery length, weaken respiration and causes other dangerous effects; its repeated use is considered unsafe. CITICOLINE is a natural substance with neuroprotective effects. Regarding the various effects of CITICOLINE on central nervous system which is the place where many anesthetics leave their effects, this research aims at studying the effects of CITICOLINE on the anesthesia induced by Thiopental SODIUM and also at Measuring the parameters such as heart and respiration rate, rectal temperature and SPO2. To do this, 6 dogs were anesthetized by intravenous injection of 20 mg ∕ kg of 2.5% Thiopental SODIUM. After the appearance of recovery signs, 250 mg of CITICOLINE was slowly injected intravenously into the experimental dogs, and immediately the second injection of Thiopental SODIUM using the initial protocol was given. Before the second injection, 2ml of normal saline was intravenously injected into the dogs in the control group.Heart and respiration rate, SPO2 and rectal temperature were then measured, recorded and statistically analyzed.Results indicated a significant increase in heart and respiration rate, an insignificant increase in SPO2 and an insignificant decrease of rectal tempreture in animals that had received citicolin before anesthesia by Thiopental SODIUM. The results of this study can be used in predicting the vital signs of patients when taking these two drugs simultaneously.

Introduction: The ever increasing and common occurrence of head traumas highlight the importance of adopting therapeutic measures for the reduction of the associated morbidity and mortality. CITICOLINE, as a safe medicine with positive effects on improving traumatic injuries, has been proven to be useful in various studies. However, there are still no data on the specific standard method and dosage of CITICOLINE for the treatment of patients with traumatic head injuries. Regarding this, the present study was performed to determine the effective therapeutic dosage of CITICOLINE and its impact on patients with traumatic head injuries. Methods: This double-blind clinical trial was performed on 30 patients with traumatic concussion (a Glasgow coma scale [GCS] of ≤ 8) admitted to the intensive care unit and neurosurgery department. The patients were randomly divided into three groups of A (control), B (CITICOLINE with a dosage of 0. 5 g/twice a day), and C (CITICOLINE with a dosage of 1. 5 g/twice a day). The GCS, degree of muscle strength, Glasgow outcome score (GOS), contusion volume, and cerebral edema (based on brain CT scans) were calculated at specific times and intervals. In addition, the patients' dependency on a ventilator and their length of ICU stay were registered. Results: Mean GCS on the first day of stay, GCS changes on the third and fourth days of stay, first and seventh days of stay, seventh and fourteenth days of stay, and first and fourteenth days of stay in the three study groups showed the significant statistical difference (P<0. 05). Significant statistical differences were seen between the GOS of the 30 day of stay in the three study groups (P<0. 05). The contusion volume difference was only significant between the first and seventh day of stay in groups A and C (P<0. 05). No significant difference was observed in the mean length of stay in ICU and duration of dependency on a ventilator in the three study groups (P<0. 05). The mean degree of muscle strength was only significantly different on the first day of stay between groups B and C (P=0. 008). th Conclusions: In contrary to similar studies, the results of the current study revealed that CITICOLINE had no positive effect on patient healing. This result may be due to the small sample size and the inconsistent first-day GCSs of the patients in all three groups. Therefore, given the confirmation of the effectiveness of CITICOLINE even at higher dosages in other studies in future studies, it is recommended to use populations with a larger number of patients.

Background and Objectives: Traumatic brain injury (TBI) is a catastrophic condition that exerts a high burden on individuals, families, and societies. The objective of this study was to systematically review the human studies on the efficacy and safety of CITICOLINE for the management of TBIs. Materials and Methods: Relevant articles were identifi, ed by searching PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials on July 1, 2022. Results: Eighteen studies met the predefined eligibility criteria, including 12 randomized controlled trials (RCTs). CITICOLINE was administered via injectional (n = 11, 61. 1%), enteral (n = 5, 27. 8%), both injectional and enteral (n = 1, 5. 5%), and unknown (n = 1, 5. 5%) routes. Numerically, studies reporting the favorable impact of CITICOLINE on patient outcome outnumbered (n = 13, 72. 2%). However, the largest RCT could not demonstrate positive results. Only two studies reported complications, and the observed difference between CITICOLINE and placebo groups was not statistically significant in either of them. Conclusion: Despite promising results in animal studies, human studies have shown inconsistent results regarding the role of CITICOLINE in TBI management. Homogeneity of patients, subgroups of patients who might benefit more, the efficacy of CITICOLINE as a part of combination therapies, and factors that could potentially influence the pharmacokinetics and brain uptake of CITICOLINE should be considered when designing future studies.

Objective(s): 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) sleep-deprived rats. Materials and Methods: Rats (n=36) were randomly divided into 6 groups. Environmental control or sleep deprivation was done by placing the rat on a 13 cm diameter platform (Large Platform [LP] group) or on a 6. 5 cm diameter platform (REMSD group), respectively, for 96 hours. Rats randomized for controls (Home Cage [HC] group) were followed up in home cages. Rats in each of the REMSD, LP or HC group were randomized to receive either saline (0, 9%NaCl) or CITICOLINE (600 μ, mol/kg) intraperitoneally twice a day for four days. After the experiments, rats were sacrificed, their cerebral cortices and hippocampi were dissected for analyzing the levels of pre-synaptic proteins synaptophysin and synapsin I, and the post-synaptic density protein-95 (PSD-95) by Western-blotting. Results: Hippocampal levels of PSD-95, but not the pre-synaptic proteins, were reduced by REM sleep deprivation. CITICOLINE treatment ameliorated the reduction in PSD-95 levels in REM sleep-deprived rats. On the other hand, REM sleep deprivation was not found to be significantly effective on pre-or post-synaptic proteins in cerebral cortex. Conclusion: REM sleep deprivation reduces hippocampal PSD-95 levels which are enhanced by CITICOLINE treatment. These data propose that CITICOLINE may ameliorate the adverse effects of SD on hippocampal synaptic functioning.

Introduction: Factors affecting hatchability are mentioned as important indicators in breeder flocks’ performance, one of these elements is fertility. Roosters’ as half part of fertility have great role and aging reduces their fertility. The biologic system in live organisms such as animals is under permanent attack due to natural consequence of the body’s normal metabolic activity that produces free radicals. It has been revealed that phospholipid fraction of avian spermatozoa membranes has high proportion of polyunsaturated fatty acids (PUFA) and it is the reason why the spermatozoa are susceptible to free radical attack. During evolution, to deal with Reactive Oxygen Species (ROS), living organisms have developed specific antioxidant protective mechanisms. Therefore, as a major factor, presence of natural antioxidants in living organisms enables their survival in an oxygen-rich environment. To maintain sperm fertilizing ability, an antioxidant defense system is a crucial point. In avian semen the antioxidant system consists of natural antioxidants together with enzymes that have antioxidant characteristics such as glutathione peroxidase (GPx) and selenoprotein P (SEPP1) protects sperm against free radicals and their destructive metabolites. Antioxidants such as vitamin E and selenium (Se) have remarkable roles in avian reproduction. To gain gross reproductive performances in commercial poultry, supplementation of antioxidant at an optimum level is thought to be necessary. By using additives such as selenium we can help delaying this reduction through antioxidant properties of Se. Replacing inorganic Se by new types of Se sources like the nano form in poultry diet improves fertility. This research was conducted to investigate the effect of Nano-Selenium (Nano-Se) in comparison with SODIUM selenite on serum selenoprotein p (SEPP1) and glutathione peroxidase (GPx) content in broiler breeder roosters.Material and Method: In the present study, a total of thirty Arbor Acres Broiler Breeder roosters (40 weeks old) were randomly divided into five experimental groups. Each of which included 3 replicates of 2 birds. Relevant catalog recommended distribution of 160 gr of diet per rooster per day for broiler breeder males. After one-week adaptation they were fed with the basal diet (T1) supplemented with 0.3 mg/kg SODIUM Selenite (T2), 0.15 mg/kg nano-Se (T3), 0.3 mg/kg nano-Se (T4) and 0.6 mg/kg nano-Se (T5). The duration of feeding experiment was four weeks. At the end of adaptation week, blood samples were collected (2.5 ml) and after separating the serum, they were stored in -20°C refrigerator. Another sampling was two weeks later in the middle of experiment that again blood samples were collected and their serum were stored at -20°C. Four weeks after the treatment was done at the end of experiment, the roosters were humanely euthanized by cervical dislocation, the 3rd and last sampling was implemented at the end of experiment that as in the previous sampling was done, the blood samples were centrifuged and separated serum was stored in -20°C. Then serum concentration of the antioxidant “SEPP1” was measured by ELISA method and “GPx” was analyzed using a spectrophotometry kit.Results and discussion: The values of SEPP1 and GPx serum concentration obtained at the first time sampling showed no significant differences between all groups (P < 0.05). Serum SEPP1 concentration examination in the second sampling showed that roosters fed with both mineral and nano form of selenium supplements, had significantly higher concentrations of selenoprotein P in their serum, compared to the control group (P < 0.05) which the highest concentration was related to the treatment of 0.6 mg/kg nano-Se (T5) in their diet. Among the two groups of treatment 2 and treatment 3, which were fed 0.3 mg/kg SODIUM selenite (T2) and 0.15 mg/kg nano-Se (T3), respectively, treatment 3 had higher concentration. The results of examining the SEPP1 serum concentration for the final time at the end of the study indicated that there is a process similar to the trend of changes in the serum concentration of selenoprotein P that was seen in the second sampling step. The only difference observed in serum concentration results of the second sampling compared to third time was that the difference between the T2 and T3 treatments was greater in the last sampling. Simultaneously with SEPP1 analysis, serum glutathione peroxidase concentration was measured in three sampling times. At the second time sampling of serum GPx concentration, evaluation of the serum concentration of glutathione peroxidase revealed that the serum concentrations of this selenoprotein in broiler breeder roosters in groups T5, T4, T3 and T2 were significantly (P < 0.05) higher relative to its concentration in control group (T1). The difference between serum concentration of control group and T3 treatment was not significant (P < 0.05), also the difference in serum concentration of this selenoprotein between treatments T4 and T5 was not significant (P < 0.05). At the end of the study, after the third sampling and evaluation, the results of GPx serum concentrations revealed that all treatments showed a significant increase compared to the control group (P < 0.05) and with increasing the amount of nano-Se in the diet from 0.15 mg/kg to 0.6 mg/kg nano-Se, serum concentrations of glutathione peroxidase showed an increasing trend. Based on a consideration of all experiment indexes, in this research 0.6 mg/kg is suggested to be the best level of supplementation of nano-Se, and nano-Se showed higher contents of serum SEPP1 and GPx at the same amounts of nano-Se and SODIUM selenite supplementation. In conclusion, dietary supplementation of nano-Se was more effective than SODIUM selenite on serum SEPP1 and GPx concentration of tested selenoproteins in broiler breeder males.

Background and Objective: Stroke and chronic cerebral hypoperfiusion (CCH) is one of the most common problems following ageing. Using the suitable treatment has been one of the issues in treating these complications. Therefore, in this study, we investigated the effects of CITICOLINE on memory and neuronal survival in CCH rats.Materials and Methods: 40 rats were divided into four groups (n=10) including: 1) Control, Rats that received vehicle after sham surgery 2) CITICOLINE: Rats that received CITICOLINE after sham surgery 3) Hypoperfusion: which underwent CCH surgery and received vehicle and 4) Hypoperfusion+CITICOLINE group, which underwent CCH surgery and then received CITICOLINE.for 10 days  (100 mg/kg). Morris water maze (MWM) and Nissl staining were used to evaluate spatial memory and hippocampal neuronal density in rats, respectively. For data analyzing, two-way ANOVA (for trial test of MWM) and one-way ANOVA (for the other data) were used.Results: The results of the Morris water maze test showed that CITICOLINE treatment increases the time spent in the target zone in hypoperfused rats (P<0.05). Histological studies (Nissl staining) showed that treatment with CITICOLINE increases the number of hippocampal neurons in the CA1 region in CCH rats (P<0.05).Conclusion: CITICOLINE treatment improves spatial memory and hippocampal neurodegeneration in CCH rats.