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Item type: Item , ارزیابی برون تنی ریزذرات حاوی کاربامازپین و فوق متلاشی سازها تهیه شده با استفاده از روش تبلورسازی کروی(دانشگاه علوم پزشکی تبریز، دانشکده داروسازی, 1388) تجلی بخش, عطیه السادات; مقصودی, مریمهدف از مطالعه حاضر تهیه و ارزیابی آگلومره های کروی کاربامازپین- فوق متلاشی سازها، با استفاده از روش کریستالیزاسیون کروی بود، تا فراهمی زیستی این دارو افزایش پیدا کند. تکنیک کریستالیزاسیون کروی روشی ساده و کارآمد است که تا کنون برای بهبود خواص میکرومریتیک و تغییر در الگوی رهش داروها بکار رفته است. اتانول، آب و ایزوپروپیل استات به عنوان سیستم کریستالیزاسیون انتخاب شدند که به ترتیب نقش حلال قوی، حلال ضعیف و مایع پل ساز را ایفا کردند.تاثیر دو نوع فوق متلاشی ساز مختلف سدیم استارچ گلیکولات و کراس کارملوز سدیم، و یک پلیمر هیدروفیل به نام پوویدون که در فرمولاسیون های مختلف و غلظت های متنوع استفاده شدند، مورد بررسی قرار گرفت. آگلومره های بدست آمده از نظر خواص میکرومریتیک، رهش و تغییرات پلی مورفیسم به کمک تست های مختلف از قبیل ریزش پذیری، دزانتگراسیون، انحلال، آنالیز حرارتی، تفرق اشعه ایکس و FT-IR مورد ارزیابی واقع شدند. نتایج نشان داد که آگلومره ها به علت شکل کروی و افزایش اندازه ذره ای، ریزش پذیری بهتری نسبت به داروی اولیه داشتند. تست دزانتگراسیون اثربخشی بیشتر کراس کارملوز سدیم را نسبت به سدیم استارچ گلیکولات در کاهش زمان دزانتگراسیون نشان داد، که به علت قدرت تورم بیشتر این ماده است. پوویدون از فعالیت فوق متلاشی سازها در آگلومره ها ممانعت بعمل می آورد، که این اثر می تواند به دلیل قدرت این ماده در افزایش ویسکوزیته و همچنین کاهش تخلخل آگلومره های حاوی آن باشد. مطالعات رهش حاکی از بهبود انحلال آگلومره های کاربامازپین نسبت به داروی خالص، به علت ساختار متخلخل آنها بود. اگرچه کراس کارملوز سدیم در مقایسه با سدیم استارچ گلیکولات در کاهش زمان دزانتگراسیون موثرتر عمل کرد، سدیم استارچ گلیکولات تاثیر بیشتری در بهبود سرعت انحلال داشت. این امر احتمالا بدلیل وقوع تداخل بین بارها در دارو و کراس کارملوز سدیم است.اما افزایش غلظت سوپردزانتگران ها از %5 به %10 و %15 در فرمولاسیون ها اثر معنی داری در بهبود سرعت انحلال نداشت (p>05/0)، که به علت خاصیت چسبانندگی این مواد می تواند باشد. همچنین اضافه کردن پوویدون به دلیل افزایش ضخامت لایه دیفوزیون و زمان دزانتگراسیون و کاهش تخلخل ذرات اثر منفی بر رهش داشت. نتایج DSC،XRPD و FT-IRنشان داد که تغییرات پلی مورفیسم در حین کریستالیزاسیون رخ داده است. در کل آگلومره های کاربامازپین- اکسیپیان ها با روش کریستالیزاسیون کروی تهیه شدند که این ذرات بهبود معنی داری در ریزش و تراکم پذیری داشتند. با تنظیم غلظت پوویدون و دزانتگران می توان به رهش دلخواه دست یافت. بنابراین آگلومره ها می توانند به طور مستقیم و بدون نیاز به هیچ پروسه ی اضافه ای تهیه شوند.Item type: Item , تهيه ميكروسفرهاي انسولين خوراكي حاوي مهار كننده پروتئاز و ارزيابي جذب درون تن ميكروسفرها در مدل موش صحرايي(دانشگاه علوم پزشکی تبریز، دانشکده داروسازی, 1388) آذری مطلق, زهرا; نخودچي, علي; جلوه‌گري, ميترا; ذاکری میلانی, پروين; سياهي, محمدرضاانسولین هورمونی پپتیدی است که برای کنترل قندخون افراد دیابتی از راه زیر جلدی تجویز می‌گردد.هدف از این مطالعه بررسی کارایی پلیمرهای اودراژیت S100وL100-55 در دارورسانی خوراکی انسولین به همراه مهارکننده پروتئاز می باشد. میکروسفرهای انسولین با روش امولسیون مضاعف به صورت تبخیر حلال (W/O1/O2) و نانوسفرها با روش کواسرواسیون کمپلکس تهيه شدند. در تهيه ميکروسفر، اتانول و پارافین مایع به ترتیب به عنوان فازهای آلی اولیه و ثانویه انتخاب شدند. در میکروسفرها تاثير نسبت های مختلف پليمر به دارو و در نانوسفرها اوزان مولکولی مختلف کیتوزان بکاررفته بر روي خصوصيات ميکرومرتيک فرمولاسيون ها مانند ميزان بارگيري، کارآيي بارگيري و اندازه ذره اي بررسي شد. همچنين با استفاده از دستگاه هایCircular Dichroism spectrophotometer (CD) Transform Infrared spectroscopy (FTIR) Fourier،Zeta sizer , (SEM) Scanning Electron Microscopy خصوصيات ميکروسفرها و نانوسفرها مطالعه گرديد. بعد از انتخاب بهترین فرمولاسیون ، اثر محافظت کنندگي مهارکننده پروتئاز (آپروتينين) بر روي انسولين موجود در فرمولاسيون ها ، بطور برون تن (در حضورآنزيم هاي پپسين و تريپسين) و درون تن در موش صحرايي بررسي گرديد. در میکروسفرها ، فرمولاسیون F2 (نسبت دارو به پلیمر 6/15 : 1 ) و در نانوسفرها نمونه تهیه شده با کیتوزان با وزن مولکولی بالا به عنوان نمونه های منتخب بدست آمدند. بررسی آزاد سازی دارو دربافر اسیدی ( 2/1 pH) و بافر بازی) 4/7 pH ( براي هر دو ميکروسفر و نانوسفر انجام گردید. نانوسفرها نسبت به ميکروسفرها رهش انفجاري کمتري نشان دادند (05/0p<). میزان داروی بار گیری شده در ميکروسفر منتخب (36/77%)، مقدار بازده توليد (55/54%)و اندازه ی ذرات آن 388/222 میکرون بدست آمد. میزان داروی بار گیری شده در نانوسفر منتخب(38/3%)، مقدار کارایی بارگیری (56/30%)و اندازه ی ذرات آن 64/199 نانومتر بدست آمد همچنین SEM نشان داد که میکروسفرهای حاصل کروی و منفذدار می باشند. در بررسی طیف CD در نانوسفرهاي انسولين فرم α- هليکس افزايش نشان داد. در بررسی کینتیک آزاد سازی دارو، با برازش داده های مربوط به رهش دارو به مدل های کینتیکی ، بهترین مدل براي کليه ميکروسفرهاي انسولين، مدل درجه اول بود و مکانيسم آزادسازي از نوع فرسايش بود. در نانوسفرها مدل هاي مختلف کينتيکي مشاهده شد.Item type: Item , Effects of cytoplasmic recombinant protein expression (hll-2&mll-4) on hydrogen peroxide concentration and catalase activity in Escherichia coli(Tabriz University of Medical Sciences, Faculty of Pharmacy, 2009) Mehdizadeh Aghdam, Elnaz; Hejazi, Mohammad SaeidThe expression of a foreign protein(s) in a recombinant host cell or organism often changes the biochemistry and physiology of the host and lower the amount of the target foreign protein. Identification of preventive factors helps to resolve their inhibitory effects and improve the product yield by increasing cell growth and recombinant proteins production from molecular cloning to bioprocess procedures.The Reactive oxygen species (ROS) is induced in the cells following various stresses. However, the effect of recombinant protein expression on ROS generation has not been studied yet. In this study, H2O2 concentration and catalase activity variations and their correlation with cell growth following cytoplasmic expression of human interleukin-2 (hIL-2) and mouse interleukin-4 (mIL-4) in Escherichia coli Bl21(DH3) were investigated. Additionally, the effect of recombinant protein expression under different conditions was compared to the effect of foreign DNA introduction on these factors. Plasmids pEThIL-2 and pETmIL-4 were used for expression of human interleukin-2 (hIL-2) and mouse interleukin-4 (mIL-4) inside the cytoplasm of the cells. Having confirmed protein expression, H2O2 concentration and catalase activity were measured at various ODs. Also, Hydrogen peroxide concentration was measured in interleukin-4 expressing and wild type cells which treated with different concentrations of IPTG. Empty vector introduction increased significantly H2O2 concentration of the cells. However, H2O2 concentration in hIL-2 and mIL-4 expressing cells was significantly higher than its concentration in empty vector transformed cells. Catalase activity was reduced in foreign DNA introduced cells. It was more lowered following expression of recombinant proteins. Results of this study revealed the relationship between foreign DNA introduction and protein expression with H2O2 elevation and catalase activity reduction. There was also correlation between H2O2 elevation and reduction in catalase activity with the cell growth depression and recombinant protein production amount.Item type: Item , Evaluation the effects of intracereboventricular injection of riluzole and minocycline on chronic morphine- induced tolernce to the analgesic effect and apoptosis in CNs of rat(Tabriz University of Medical Sciences, Faculty of Pharmacy, 2010) Hassanzadeh, Kambiz; Safar, Farajnia; Roshangar, Leila; Habibi Asl, BohloolLong-term exposure to opiates induces tolerance to the analgesic effect. The neurobiological mechanism of this phenomenon is not completely clear. It has been indicated that neuronal apoptotic process is in association with the development of morphine tolerance. In the present study we tried to investigate the effect of intracerebroventricular (icv) administration of minocycline (a tetracycline derivative) and riluzole (an anti-glutamatergic agent) on morphine-induced tolerance and apoptosis in rat’s central nervous system. Different groups of rats received either morphine (ip) and drugs vehicle (icv) or morphine and different doses of minocycline or riluzole (icv) once per day. Nociception was assessed using a hot plate apparatus. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used to analyze apoptosis. The anti-apoptotic factors, Bcl-2 and HSP70 and the pro-apoptotic element caspase-3 were evaluated by immunoblotting. The results showed that central administration of minocycline and riluzole delayed morphine-induced tolerance. Additionally results indicated that minocycline attenuated the number of apoptotic cells in both the cerebral cortex and lumbar spinal cord. Immunoblotting findings showed that the amounts of anti-apoptotic agents (Bcl-2 and HSP70) were greater in the minocycline treated groups than in the controls in both regions. However, minocycline did not change the level of caspase-3 at the doses used with morphine. Furthermore the results showed that intracerebroventricular administration of riluzole attenuated morphine tolerance and number of TUNEL positive cells in both the cerebral cortex and lumbar spinal cord. The amount of anti-apoptotic agents (Bcl-2 and HSP70) was greater in the treatment groups than controls in both regions. Additionally, riluzole significantly decreased the caspase-3 content of the cerebral cortex. In conclusion, we found that intracerebroventricular administration of minocycline or riluzole attenuated the morphine induced tolerance and apoptosis in the cerebral cortex and lumbar spinal cord of rat.Item type: Item , Study of the effects of Acetyl L-carnitine on ischemia/reperfusion-induced arrhythmias and infarct size in isolated rat heart(Tabriz University of Medical Sciences, Faculty of Pharmacy, 2009) Ghaffary Eyrdmousa, Saba; Najafi, MoslemIntroduction: Acetyl-L-carnitine (ALC) is an ester of the trimethylated amino acid, L-carnitine, and is synthesized in the human brain, liver, and kidney by the enzyme ALC transferase. ALC facilitates the uptake of acetyl CoA into the mitochondria during fatty acid oxidation, enhances acetylcholine production, and stimulates protein and membrane phospholipids synthesis. ALC, similar in structure to acetylcholine, also exerts a cholinomimetic effect. ALC plays a major role in normal mitochondrial function, being a transport molecule for free fatty acids and an important acetyl-group donor in high-energy metabolism and free fatty acid beta-oxidation. Its main body stores are in skeletal and cardiac muscle. It is found along with free plasma L-carnitine and other acyl-esters of varying chain length and has been claimed to be superior to normal L-carnitine in terms of bioavailability. This study aimed to examine whether ALC was able to reduce cardiac arrhythmias and myocardial infarction size in ischemic-reperfused isolated rat heart. Method & materials : Male Wistar rats weighing 270-330 g were used in this study. The rats were pretreated with intraperitoneal (ip) injection of 300 IU heparin then anaesthetized by sodium pentobarbital (60 mg/kg, ip). The hearts were excised rapidly and mounted on a non-recirculating langendorff apparatus under 100 mmHg pressure at 37 °C and perfused throughout the experiments with modified Krebs-Henseleit (K/H) solution which was previously equilibrated with 95% O2 - 5% CO2. A fluid filled balloon introduced into the left ventricle and inflated to give a preload of 8–10 mmHg . After 20 min stabilization, the hearts subjected to 30 min regional ischemia followed by 120 min reperfusion. In control group (n=8-10), the hearts perfused only by normal K/H solution throughout the experiment, while in the treatment groups (4 groups, n=8-10 in each group), they were perfused during I/R with enriched K/H solution with 0.375, 0.75, 1.5 and 3 mM of ALC, respectively. Induction of regional ischemia achieved by temporary occlusion of left anterior descending (LAD) coronary artery followed by 120 min reperfusion. An epicardial ECG was recorded by a polygraph during the experiment. Based on the Lambeth conventions, the ECGs were analyzed to determine the total number of ventricular ectopic beats (VEBs), the number of beats occurring as ventricular tachycardia (VT), and the incidence and duration of VT and ventricular fibrillation (VF) during ischemia and the first 30 min of reperfusion time. At the end of reperfusion, Evans blue solution was infused to stain the non-ischemic area. Then the hearts were cut into slices, incubated by 1% Triphenyltetrazolium chloride solution, and fixed in formalin. The infarct size was determined by using a computerized planimetry package. Results: During ischemia, all used concentrations of ALC decreased number and duration of ischemic ventricular tachycardia (VT) and number of ventricular ectopic beats (VEBs) versus the control group (p<0.01). ALC reduced the incidence of total ventricular fibrillation (VF) and the time spent for reversible VF (p<0.05). In addition, incidence of VT was significantly reduced only by 3 mM (p<0.05). At the reperfusion phase, duration of VT showed significant reduction by lower concentrations (p<0.05). Moreover, ALC (0.375, 1.5 and 3 mM) reduced the incidence of total VF from 80% (control) to 25%, 50% and 38%, respectively (p<0.05). In the control group, infarct size was 23±3.1%, however, ALC (0.375, 0.75, 1.5 and 3 mM) reduced infarct size to 8.7±2.3 (p<0.01), 5.3±1.4 (p<0.0001), 12±4.1 (p<0.05) and 8±2.9% (p<0.01). Conclusions: By considering of the results, it may be concluded that ALC has protective effects against cardiac ischemia-reperfusion injuries as reduction of infarct size and arrhythmias in isolated rat heart. Stimulation of glucose oxidation via activation of PDH, and then reducing lactate production, reduction of fatty acid metabolites in the myocytes and antioxidant effect by ALC may have important roles in this condition.Item type: Item , Effects of oral honey administration on ischemia reperfusion -induced arrhythmias and infarct size in isolated rat heart(Tabriz University of Medical Sciences, Faculty of Pharmacy, 2009) Shaseb, Elnaz; Najafi, MoslemIntroduction: Honey is widely used in folk-medicine throughout the world. However, it has a limited use in modern medicine due to lack of scientific support. Honey has demonstrated antimicrobial properties. High antimicrobial activity is as a result of osmotic effect, acidity, hydrogen peroxide and phytochemical factors, and as yet unidentified compound putatively described as inhibines, although lethality of and inhibition by these and other components against microorganisms vary greatly, depending on the floral source of nectar. Honey has been reported to have an inhibitory effect to around 60 species of bacteria including aerobes and anaerobes, gram-positives and gram-negatives. An antifungal action has also been observed for some yeasts and species of Aspergillus and Penicillium, as well as all the common dermatophytes. Honey has antioxidant activity. In general, the antioxidant capacity of honey appeared to be a result of the combined activity of a wide range of compounds including phenolics, peptides, organic acids, enzymes, Maillard reaction products, and possibly other minor components. The phenolic compounds contributed significantly to the antioxidant capacity of honey but were not solely responsible for it. There is no report regarding cardioprotective effects of chronic oral administration of natural honey against ischemia/reperfusion (I/R) injuries. Therefore, in this thesis, effects of chronic oral honey on I/R- induced cardiac arrhythmias and infarct size were investigated in isolated rat heart. Materials and Methods: Male Wistar rats weighing 270-300 g were divided into four groups (n=10 in each group) and fed with different concentrations of honey (1%, 2% and 4%) for 45 days except the control group. After anesthesia by sodium pentobarbital (60 mg/kg, i.p.), the hearts were excised rapidly and mounted on a Langendorff apparatus under 100 mmHg pressure at 37 °C and perfused throughout the experiments with modified Krebs-Henseleit (K/H) solution. A fluid filled balloon introduced into the left ventricle and inflated to give a preload of 8–10 mmHg. After 20 min stabilization, the hearts subjected to 30 min regional ischemia followed by 120 min reperfusion. An epicardial ECG was recorded by a polygraph during the experiment. Based on the Lambeth conventions, the ECGs were analyzed to determine cardiac arrhythmias. At the end of reperfusion, Evans blue solution was infused to stain the non-ischemic area. Then the hearts were cut into slices, incubated by 1% thriphenyl tetrazolium chloride solution, and fixed in formalin. The infarct size was determined by using a computerized planimetry package. Results: Administration of oral honey (1% and 2%) reduced infarct size from 23±3.1% (control) to 9.7±2.4 and 9.5±2.3%, respectively (p<0.001). In the ischemic phase, administration of oral honey (1% and 2%), was reduced the number of VT from 473±166 in the control group to 26±14 (p<0.01) and 72±54 (p<0.05), respectively. Duration of VT was decreased by the same concentrations (p< 0.01 and p<0.05, respectively). Honey (1% and 2%) also led to a reduction in the number of ventricular ectopic beats (VEBs) from 941±224 (control) to 421±143 and 241±116 (p<0.05 and p<0.01), respectively. Duration and incidence of reversible ventricular fibrillation (Rev VF) were decreased statistically significant by honey 2% (p<0.05). In addition, honey (1% and 2%) caused significant reduction in the incidence of VT and total VF compared to the control group (p<0.05). During reperfusion time, VT incidence was 73% in the control group, however natural honey (1%) decreased it to 22% (p<0.05). In addition, total VF incidence, time and number of VT were decreased significantly by the same concentration (p<0.01). In addition, Rev VF incidence was lowered significantly from 82% (control) to 33% by 1% and 2%, respectively (p<0.05). Discussion and Conclusions: For the first time, results of present study demonstrated protective effects of chronic oral honey administration against ischemia/reperfusion injuries in isolated rat heart as reduction of infarct size and arrhythmias. Maybe, antioxidant activity, the existence of various components especially important minerals, energy sources such as glucose and fructose and some improvement in hemodynamic functions may have important roles in these protective effects.Item type: Item , Determination of solubility of phenanthrene in binary and ternary solvent mixtures and application of the Jouyban-Acree model for solubility prediction of chemical/drug compounds in mixed solvents(Tabriz University of Medical Sciences, Faculty of Pharmacy, 2010) Abolghassemi Fakhree, Mohammad Amin; Jouyban, AbolghasemSolubility of a compound in a solvent is an important thermodynamic property in chemical and pharmaceutical sciences. Its major effects can be seen in chemical and pharmaceutical related properties and processes such as synthesis, extraction, purification, crystallization, analysis, formulation, absorption, distribution, metabolism, elimination, and toxicity. Different methods of solubilization are applied to modify this property such as altering temperature, cosolvency, micelization, and complexation. Cosolvency and temperature altering are most accessible methods to modify solubility amount. Numerical methods have been introduced during recent decades; some of these calculative methods were structured, based on only empiric data correlation, some based on empiric data and theoretical models, and some other are based on theoretical calculations. For example, the linear solvation energy relationship (LSER) quantitative structure property relationships (QSPRs) of Abraham were developed based on solvatochromic properties of solvents and solutes and are used for solubility prediction in mono-solvents. Catalan solvent parameters are another set of solvatochromic properties which have been measured for more than 200 solvents. The Jouyban-Acree model is the most accurate semi-empirical model for solubility prediction in non-aqueous binary or multi-component solvents mixtures. In an attempt, coefficients of the Jouyban-Acree model for non-aqueous binary mixtures have been described using Abraham solvent and solute parameters. Phenanthrene is a polycyclic aromatic hydrocarbon (PAH) which can be used as a substrate for synthesis of medicinal compounds and is a model solute in solubility studies. As a part of QSPR modeling of this work, we are going to define Catalan solute parameters based on solubility amounts of a solvent in more than 8 solvents with known Catalan solvent parameters, using a multiple linear regression approach. The solubility data of phenanthrene in alcohols at different temperatures is measured. Another part of this study includes measurement of experimental solubility data for phenanthrene in different non-aqueous binary and ternary solvent mixtures and checking the predictability of the Jouyban-Acree model combined with Abraham parameters. To do this, four different numerical methods have been described. Using experimental solubility data in mono-solvents, numerical method I and II have been defined employing water-to-solvent and gas-to-solvent Abraham parameters, respectively. Predicted solubility amounts using Abraham parameters in mono-solvents and numerical method III and IV have been defined employing water-to-solvent and gas-to-solvent Abraham parameters, respectively. The mean percentage deviation has been used as an error criterion. The overall mean percentage deviations are 3.4 %, 14.6 %, 11.1 %, and 93.8 % for numerical methods I to IV, respectively. In all parts of experiment, phenanthrene has been recycled and reused. The results of this study suggest that the Jouyban-Acree model can be applied for solubility prediction in non-aqueous binary and ternary solvent mixtures with acceptable prediction error. To make it easy-to-use for chemical and pharmaceutical scientists and researchers, developing computer software might be a useful method.Item type: Item , Study of Drug Release from Smart Mucoaahesive Nanoparticles Containing Nonsteroidal Anti Inflammatory Drugs for Use in Ophthalmic Formulations(Tabriz University of Medical Sciences, Faculty of Pharmacy, 2010) Pashapour, Tannaz; Alizadeh Ghavidel, Leila; Davaran, Soudabeh; Javadzadeh, YusefIntroduction:The potential of polymeric nanoparticles as an ocular drug delivery system has been explored by a colloidal system consisting of an aqueous suspension of nanoparticles. These nanoparticles can be rapidly fabricated under extremely mild conditions with their ability to incorporate bioactive compounds. In present study the preparation and characterization of the novel cross-linked poly N-isopropylacrylamide-based micellar nanoparticles have been reported. Methods: Poly (N-isopropylacrylamide-acrylic acid-hydroxyethyl methacrylate) [Poly (NIPAM-AA-HEM)] and Poly (N-isopropylacrylamide-acrylic acid-vinyl pyrrolidone) [Poly (NIPAM-AA-VP)] copolymers were synthesized by free radical copolymerization of monomers in 1, 4-dioxane under N2 atmosphere. Triethylene glycol dimethacrylate (TEGDMA) was used as a novel cross-linking agent. For preparation of drug-loaded nanoparticles indomethacin got directly loaded into the hydrophobic core of micelles. Drug incorporation efficiency was expressed as drug content (DL %).In-vitro indomethacin release rate was tested using basket apparatus on a dissolution tester.Results: The chemical structures of cross-linked polymers were confirmed by FT-IR and 1H NMR spectroscopies. The PSA data represented that the particles has mean sizes between 200-470 nm. The maximum swelling ratio of hydrogel occurred at 10 min at 37 ?C and pH 1.0 and at 125 min at 20 ?C and pH 1.0. For all the formulations, the release rate was related to the drug-to-polymer ratio.For both P (NIPAAM-AA-HEM) and P (NIPAAM-AA-VP) preparations, a progressive increase of drug release rate was observed as a function of drug-polymer ratio.Conclusion: The prepared nanoparticles were stable in an aqueous solution and maintained their physical characteristics such as particle size and drug loading content during seven days of storage. It was demonstrated that the degree of in vitro indomethacin release from the PNIPAAM-based nanoparticles in pH 6.4 PBS buffer depended on the degree of drug loading.Key words: Indomethacin, poly N-isopropylacrylamide, micellar nanoparticles, in-vitro releaseItem type: Item , Omeperazole-induced cytotoxicity in isolated rat hepatocytes(Tabriz University of Medical Sciences, Faculty of Pharmacy, 2015) Ghorbani, Sahba; Heidari, Reza; Eghbal, MohammadaliIntroduction:The liver is central to the metabolism of virtually every foreign substance. Most drugs and xenobiotics are lipophilic, enabling them to cross the membranes of instinal cells. Drugs are rendered more hydrophilic by biochemical processes in the hepatocyte , yielding water – soluble products that are excreted in urine or bile. Most drugs cause liver injury infrequently. Metabolism of a xenobiotic chemical following its exposure can alter it , leading to its detoxification and excretion and/ or enhance its toxicity due to the activation of the compound. The liver is prone to drug-induced hepatotoxicity as it is exposed to high concentrations of drugs and other xenobiotics absorbed from gastrointestinal tract. Omeprazole is used to treat symptoms of gastroesophageal reflux disease (GERD) and other conditions caused by excess stomach acid. It is also used to promote healing of erosive esophagitis . Omeprazole administration is associated with hepatotoxic reactions in some patients. Aim:The aim of this study was the evaluation of cytotoxicity of omeprazole in isolated rat hepatocytes. Method:In this study, the cytotoxic effects of omeprzole was evaluated. Markers such as cell death, reactive oxygen species (ROS) formation, lipid peroxidation , mitochondrial membrane potential , were inversigated. Result: It was found that the drug caused cytotoxicity towards rat hepatocytes concentration – dependently.This study suggests that the adverse effect of studies drug towards hepatocytes is mediated through oxidative stress and the heapatocytes mitochondria play an important role in omeprazole's toxicity. Conclusion:Omeprazole should be administered in patients with hepatic disease with great caution and hepatic functions.and should be monitored regularly in these patients.Item type: Item , ارزیابی تاثیر پیشگیرانه سفتریاکسون و پرگابالین بر درد نوروپاتیک ناشی از وین کریستین در موش سوری(دانشگاه علوم پزشکی تبریز، دانشکده داروسازی, 1398) زال پور, پویا; حبیبی اصل, بهلول; محجل نائبی, علیرضامقدمه: فعال شدن کانالهای کلسیمی و سیستم گلوتامینرژیک و سرتونرژیک و استرس اکسیداتیو از مکانیسم های مهم در پیدایش نوروپاتی القاء شده توسط داروی وین کریستین می باشد. سفتریاکسون و پرگابالین به ترتیب افزایش بیان ژنی ترانسپورترهای گلوتامات و اثر آنتی اکسیدانی دارند. هدف: هدف از مطالعه حاضر بررسی اثرات با هم سفتریاکسون و پرگابالین بر نوروپاتی حاصل از وین کریستین بود. مواد و روش کار: تعداد 72 سر موش سوری نر در محدوده وزنی 35-25 گرم به صورت تصادفی در 9 گروه 8 تایی تقسیم شدند. دوزهای مختلفی از پرگابالین ) mg/kg,ip 10،20،40 ) و سفتریاکسون (mg/kg,ip50،75،100 ) و تجویز توام (پرگابالین mg/kg,ip10 + سفتریاکسونmg/kg,ip 50) در سه روز اول و یک روز قبل از دریافت وین کریستین (mg/kg,ip2) صورت پذیرفت. در ارزیابی تاثیر رژیم های مختلف در ازدیاد حساسیت به درد از آزمون (tail flick) استفاده بعمل آمد. در پایان سطح سرمی malondialdehyde (MDA) و (TAC) مورد ارزیابی قرار گرفت. نتایج: دوزهای مختلف از پرگابالین و سفتریاکسون موجب تاثیرات معنی داری در کاهش نوروپاتی ناشی از وین کریستین شد و در تجویز توام پرگابالین (mg/kg,ip 10 ) به همراه سفتریاکسون (mg/kg,ip50) تاثیرات معنی-داری نسبت به تجویز به تنهایی پرگابالین 10 مشاهده شد. وین کریستین موجب افزایش معنی داری در سطح MDA شد. (P<0/05) پرگابالین) mg/kg,ip 10،20،40 ) وسفتریاکسون (mg/kg,ip50،75،100( موجب کاهش معنی داری در سطح MDA و افزایش TAC نسبت به گروه کنترل گردند.(P<0.05) نتیجه گیری: احتمالاً سفتریاکسون با افزایش بیان ژنی ترانسپورترهای گلوتامات و پرگابالین با اثر بر کانال های کلسیمی و فعالیت آنتی اکسیدانی و آثار ضد التهابی در پیشگیری از نوروپاتی ناشی از وین کریستین موثر می باشند.