REVIEW_ARTICLE Thromboembolic disease is a common cause of morbidity and mortality. Thrombin plays a key role in thrombotic events and thrombin inhibition represents a therapeutic event for thromboembolic events and has been identified as a target of therapy of its pivotal role in coagulation process. Anticoagulation is a major intervention for the management of arterial and venous thromboembolic events. Dabigatran etexilate is an orally effective anti-thrombin drug, several animal and human trials were conformed the efficacy of this drug in reduction of major bleeding in related to acute coronary syndrome, knee replacement surgery and venous thromboembolism conditions. The therapeutic use of this drug also shows limited side effects to select the dabigatran as promising therapeutic agent in bleeding complications. http://pbr.mazums.ac.ir/article-1-68-en.pdf 2015-12-06 1 10 10.18869/acadpub.pbr.1.3.1 Anticoagulation dabigatran Thromboembolic disease thrombin inhibition Himabindu Reddy 1 Department of Pharmacology and Pharmacy Practice, Annamacharya College of Pharmacy, Rajampet, India AUTHOR Chakka Gopinath 2 Department of Pharmacology and Pharmacy Practice, Annamacharya College of Pharmacy, Rajampet, India AUTHOR Mohamed Saleem Thattakudian Sheikuduman 3 Department of Pharmacology and Pharmacy Practice, Annamacharya College of Pharmacy, Rajampet, India AUTHOR

ORIGINAL_ARTICLE Phenylalanine (Phe) is the most reliable indicator for the diagnosis of phenylketonuria (PKU). The purpose of this study is to establish a reliable and quick method for the assignment of Phe in peripheral capillary blood from newborns and children by high performance liquid chromatography with ultraviolet detection (HPLC-UV). PKU is an inborn error of metabolism characterized by the inability of the body to use Phe. A rapid and sensitive high performance liquid chromatographic (HPLC) method has been developed for determination of Phe in plasma. The method uses a protein precipitation step with sulfosalicilic acid for sample preparation by separation on a Nova-pack C18 column using sodium acetate buffer and acetonitrile (94: 6 v/v) adjusted to pH 6.5 with glacial acetic acid. The eluted peaks detected by a UV detector was set at wavelength of 215 nm. The method was validated in the range of Phe concentrations from 0.1 to 20 µg/ml. The limits of detection (LOD) and quantitation (LOQ) of the method were 0.05 and 0.1 µg/ml, respectively. The average drug recovery from plasma was 88.60 percent throughout the linear concentration range., with the average within-run and between-run accuracy values of 103.3 and 115.350, respectively. The method is quick, easy, very steady and precise for the screen, assignment, and evaluation of Phe in human plasma by HPLC, which is particularly a useful way for screening and diagnosis of PKU and monitoring of a diet therapy. http://pbr.mazums.ac.ir/article-1-62-en.pdf 2015-10-10 11 19 10.18869/acadpub.pbr.1.3.11 Phenylketonuria (PKU) Phenylalanine (phe) assay Reversed-phase HPLC. Hossein Danafar 1 Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran AUTHOR Mehrdad Hamidi 2 Department of Pharmaceutics, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran AUTHOR

ORIGINAL_ARTICLE Ziziphus jujuba Mill (ZJ), which has been extensively used by the Iranian traditional healers, belongs to the Ramnaceae family. This semitropical herb contains large quantities of polyphenols and flavonoids, which in turn reveal antioxidant, antibacterial, free radical scavengering, and several other pharmacological activities. The purpose of the present study was to evaluate the DNA damage prevention potential of hydroalcoholic and polyphenolic extracts of Ziziphus jujuba on HepG2 cells. Throughout the assessment of genoprotective properties, cells were incubated with various concentrations of hydroalcoholic (0.1, 1, 10, and 50 µg/ml) and polyphenolic extracts (0.1 and 1 µg/ml) for a one-hour period, followed by a one-hour incubation period with genotoxic concentration of methyl methanesulfonate (MMS) (10 µM). The comet assay method was applied because of its being attributable to the substantial sensitivity, its inexpensiveness, and its straightforward procedure of use. The tail length, percentage of DNA in tail, and tail moment were measured. Statistical analysis revealed that concentrations of 10 μg/ml for hydroalcoholic extract and 1μg/ml for polyphenolic extract were genoprotective against MMS. Therefore, our results suggest that Ziziphus jujuba at suitable doses can prevent DNA damage. http://pbr.mazums.ac.ir/article-1-51-en.pdf 2015-08-30 20 30 10.18869/acadpub.pbr.1.3.20 Ziziphus Jujuba Genoprotective effect HepG2 Comet Assay. Mahmoud Etebari 1 Department of Pharmacology and Toxicology, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. AUTHOR Behzad Zolfaghari 2 Department of Pharmacognosy, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran AUTHOR Abbas Jafarian-Dehkordi 3 Department of Pharmacology and Toxicology, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. AUTHOR Afsaneh Mirzaei 4 Department of Pharmacology and Toxicology, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. AUTHOR

ORIGINAL_ARTICLE Geum iranicum Khatamsaz (Rosaceae) is an endemic plant in Iran. The infusion and decoction of the plant have been used by local people for medicinal purposes. Our previous work on phytochemical studies on G. iranicum showed that the root was rich in sugars and sucrose was identified as a major one in it. In this study, the content of sucrose in the hydro-alcoholic (1:1) extract of the root of G.  iranicum was analyzed using HPLC. The amount of sucrose has been evaluated as 31.75% in the extract and 8.16% in the dried root. As a result, the presence of high amount of sucrose in the root of G. iranicum can be applicable for preparation of any pharmaceutical formulations of this plant. http://pbr.mazums.ac.ir/article-1-69-en.pdf 2015-12-06 31 36 10.18869/acadpub.pbr.1.3.31 Geum iranicum root sucrose quantification HPLC Somayeh Shahani 1 Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Ahmad Reza Gohari 2 Medicinal Plants Research Center, Tehran University of Medical Sciences, Tehran, Iran AUTHOR Hamid Reza Monsef-Esfahani 3 Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran AUTHOR

ORIGINAL_ARTICLE Methamphetamine (MET) is a stimulant and one of the most abused drugs in worldwide. MET could cause several organ toxicity such as cardiotoxicity. Oxidative stress has been proposed as the main mechanism for MET toxicity. Propofol as a sedative-hypnotic agent has antioxidant property. In this study, we used propofol for attenuating of MET-induced cardiotoxicity in rats. The groups (six rats in each group) were as follows: control, MET (5 mg/kg IP) and treated groups that were received propofol (5, 10 and 20 mg/kg, IP) and vitamin E, 30 min before MET administration. After 24 hours, animals were killed, and heart tissue and blood were separated. MET cardiotoxicity was assessed by the evaluation of the levels of lactic acid dehydrogenase (LDH) and creatine phosphokinase (CPK) as cardiac marker enzymes. On the other hand, oxidative stress markers such as reactive oxygen species (ROS), lipid peroxidation (LPO), glutathione (GSH) and protein carbonyl were measured in heart tissue. Treatment with propofol significantly decreased the cardiac marker enzymes level which increased in MET-treated group. Propofol significantly inhibited the ROS formation and protected the cardiac tissue against LPO. Propofol also significantly prevented MET induced GSH oxidation in cardiac tissue. Protein carbonyl level was increased after MET exposure, but was significantly decreased with propofol pre-treatment. This study showed that propofol prevented MET-induced cardiotoxicity via inhibition of oxidative stress damage. Therefore, the efficacy of this antioxidant could be evaluated for the treatment of MET toxicity situation. http://pbr.mazums.ac.ir/article-1-70-en.pdf 2015-12-09 37 46 10.18869/acadpub.pbr.1.3.37 Methamphetamine cardiotoxicity propofol oxidative stress cardiac enzyme Fatemeh Shaki 1 Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Motahareh Koohsari 2 Research Student Committee, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR

ORIGINAL_ARTICLE A rapid and sensitive liquid chromatography–tandem mass spectrometry (LC-MS) method was developed for the determination of enalapril and enalaprilat in human plasma. Detection of analytes was achieved by tandem mass spectrometry with electrospray ionization (ESI) interface in positive ion mode which was operated under the multiple-reaction monitoring mode. Sample pretreatment was involved in a one-step protein precipitation (PPT) with per chloric acid of plasma. The reconstituted samples were chromatographed on C18 column by pumping methanol: water: acid formic 74:24:2 (v/v) at a flow rate of 0.2 mL/min. Each plasma sample was chromatographed within1.25 min. The standard curves were found to be linear in the range of 0.1–20 ng/mL of enalapril and enalaprilat with mean correlation coefficient of ≥0.999 for each analyte. The intra-day and inter-day precision and accuracy results were well within the acceptable limits. The limit of quantification (LOQ) was 0.1ng/ml for enalapril and enalaprilat. The lower limit of detection (LOD) was 0.08 ng/ml for enalapril and enalaprilat. http://pbr.mazums.ac.ir/article-1-71-en.pdf 2015-12-09 47 58 10.18869/acadpub.pbr.1.3.47 Enalapril e nalaprilat LC - MS h uman plasma Hossein Danafar 1 Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran AUTHOR Mehrdad Hamidi 2 Department of Pharmaceutics, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran AUTHOR

ORIGINAL_ARTICLE In this study the effect of liquisolid technique on the dissolution profile of spironolactone was evaluated. Different formulations of spironolactone liquisolid compacts were prepared using various amounts of non-volatile vehicles (Poly ethylene glycol 400 and glycerin). The ratio of microcrystalline cellulose (as carrier) to silica (as coating powder material) was 20 for all formulations. After preparing tablets by direct compression with constant compression load, the release profiles were evaluated by USP paddle method. Differential scanning calorimeter (DSC) and FTIR were used to evaluate any interaction between spironolactone and other ingredients. The liquisolid tablets exhibited significantly higher dissolution rates in comparison with conventionally direct compressed tablets. Furthermore results showed dissolution rate enhancement of liquisolid tablets by increase in the amounts of non-volatile vehicles. Differential scanning calorimetry showed that, the drug has got solubilized in the liquid vehicle. FT-IR spectroscopy studies of pure spironolactone, liquisolid compacts, glycerin and PEG400 supported solubilization of the drug in the liquid vehicle too. The FT-IR spectra also showed that no interactions have been occurred between spironolactone and other ingredients. In conclusion the liquisolid technique can be a suitable method in order to prepare rapid release tablets of poorly water-soluble drugs such as spironolactone. http://pbr.mazums.ac.ir/article-1-72-en.pdf 2015-12-16 59 70 10.18869/acadpub.pbr.1.3.59 Spironolactone liquisolid technique dissolution rate PEG 400 Jafar Akbari 1 Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Majid Saeedi 2 Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Katayoun Morteza-Semnani 3 Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Zaynab Sadeghi Ghadi 4 Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Seyed Saeed Hosseini 5 Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR