فهرست مطالب

Advanced Pharmaceutical Bulletin - Volume:6 Issue:4, 2017
  • Volume:6 Issue:4, 2017
  • تاریخ انتشار: 1395/10/15
  • تعداد عناوین: 20
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  • Hadi Hamishehkar, Farhad Ranjdoost, Parina Asgharian, Ata Mahmoodpoor, Sarvin Sanaie* Pages 467-477
    The consumption of a daily multivitamin among people all over the world is dramatically increasing in recent years. Most of the people believe that if vitamins are not effective, at least they are safe. However, the long term health consequences of vitamins consumption are unknown. This study aimed to assess the side effects and possible harmful and detrimental properties of vitamins and to discuss whether vitamins can be used as safe health products or dietary supplements. We performed a MEDLINE/PubMed, EMBASE, Scopus and Google Scholar search and assessed reference lists of the included studies which were published from 1993 through 2015. The studies, with an emphasis on RCTs (randomized controlled clinical trials), were reviewed. As some vitamins such as fat-soluble vitamins (vitamin A, vitamin D, vitamin E), and also some of the water-soluble vitamins like folic acid may cause adverse events and some like vitamin C is widely taken assuming that it has so many benefits and no harm, we included relevant studies with negative or undesired results regarding the effect of these vitamins on health. Our recommendation is that taking high-dose supplements of vitamins A, E, D, C, and folic acid is not always effective for prevention of disease, and it can even be harmful to the health.
    Keywords: Vitamins, Dietary Supplements, Drugs, Complementary Therapies, Safety, Adverse effects
  • Dipak Dilip Gadade *, Sanjay Sudhakar Pekamwar Pages 479-494
    Cocrystal is a concept of the supramolecular chemistry which is gaining the extensive interest of researchers from pharmaceutical and chemical sciences and of drug regulatory agencies. The prominent reason of which is its ability to modify physicochemical properties of active pharmaceutical ingredients. During the development of the pharmaceutical product, formulators have to optimize the physicochemical properties of active pharmaceutical ingredients. Pharmaceutical cocrystals can be employed to improve vital physicochemical characteristics of a drug, including solubility, dissolution, bioavailability and stability of pharmaceutical compounds while maintaining its therapeutic activity. It is advantageous being a green synthesis approach for production of pharmaceutical compounds. The formation polymorphic forms, solvates, hydrates and salts of cocrystals during the synthesis reported in the literature which can be a potential issue in the development of pharmaceutical cocrystals. The approaches like hydrogen bonding rules, solubility parameters, screening through the CSD database or thermodynamic characteristics can be utilized for the rational design of cocrystals and selection of coformers for synthesis multi-component cocrystals. Considering the significance of pharmaceutical cocrystals pharmaceutical regulatory authorities in the United States and Europe issued guidance documents which may be helpful for pharmaceutical product registration in these regions. In this article, we deal with the design, synthesis, strategic aspects and characteristics of cocrystals along perspectives on its regulatory and intellectual property considerations.
    Keywords: Cocrystal, Crystal engineering, Solubility, Drug Stability, Crystallization polymorphism, Salt
  • Ramin Raoufinia, Ali Mota, Neda Keyhanvar, Fatemeh Safari, Sara Shamekhi, Jalal Abdolalizadeh* Pages 495-507
    As the most frequent plasma protein, albumin constitutes more than 50% of the serum proteins in healthy individuals. It has a key role in oncotic pressure maintenance and it is known as a versatile protein carrier for transportation of various endogenous and exogenous ligands. Reduced amounts of albumin in the body will lead to different kinds of diseases such as hypovolemia and hypoproteinemia. It also has various indications in shocks, burns, cardiopulmonary bypass, acute liver failure and etc. Further applications in research consist of cell culture supplement, drug delivery carrier and protein/drug stabilizer. So, the demand for albumin increased annually worldwide. Due to different applications of albumin, many efforts have been accomplished to achieve albumin during a long period of time. In this review, an overview of serum albumin and different purification methods are summarized.
    Keywords: Human serum albumin, Purification, Chromatography, Immunoaffinity
  • Yunes Panahi, Simin Dashti, Khavidaki, Farahnoosh Farnood, Hamid Noshad, Mahsa Lotfi, Afshin Gharekhani * Pages 509-514
    Uremic pruritus remains one of the most tormenting, frequent and potentially disabling problem in chronic kidney disease (CKD) patients. However, an area of substantial etiological interest with relation to uremic pruritus is the essential fatty acids deficiency. So we performed a literature review to elucidate the efficacy of omega-3 fatty acids on uremic pruritus. This review evaluated all of the studies published in English language, focusing on the clinical effects of omega-3 fatty acids on uremic pruritus. The literature review was conducted in December 2015 and carried out by searching Scopus, Medline, Cochrane central register of controlled trials, and Cochrane database of systematic reviews. The search terms were "kidney injury", "kidney failure", "chronic kidney disease", "end-stage renal disease", "dialysis", "hemodialysis", "peritoneal dialysis", "pruritus", "itch", "skin problems", "fish oil", "omega 3", "n-3 fatty acids", "polyunsaturated fatty acids", "docosahexaenoic acid", and "eicosapentaenoic acid". Four small studies investigating potential benefits of omega-3 fatty acids on symptoms of uremic pruritus were found. Among them, three small randomized controlled trials have shown a significant improvement in pruritus symptoms (evaluated by a standard questionnaire) in CKD patients who took omega-3 supplement compared to omega-6, omega-9, and placebo supplementation. Despite numerous limitations of the studies, it is worth noting that even minor reduction in itching symptoms may be clinically significant for CKD patients. Therefore, and considering multiple health benefits of omega-3 fatty acids in advanced CKD and negligible risk profile, omega-3 intake can wisely be applied to CKD patients with uremic pruritus.
    Keywords: Chronic Kidney Disease, Omega-3 fatty acids, Pruritus, Supplement, Uremia
  • Reza Kazemi Oskuee, Asma Mahmoudi, Leila Gholami, Alireza Rahmatkhah, Bizhan Malaekeh, Nikouei * Pages 515-520
    Purpose
    Cationic polymers and cationic liposomes have shown to be effective non-viral gene delivery vectors. In this study, we tried to improve the transfection efficiency by employing the advantages of both.
    Methods
    For this purpose, modified polyallylamines (PAAs) were synthesized. These modifications were done through the reaction of PAA (15 KDa) with acrylate and 6bromoalkanoic acid derivatives. Liposomes comprising of these cationic polymers and cationic lipid were prepared and extruded through polycarbonate filters to obtain desired size. Liposome-DNA nanocomplexes were prepared in three carrier to plasmid (C/P) ratios. Size, zeta potential and DNA condensation ability of each complex were characterized separately and finally transfection efficiency and cytotoxicity of prepared vectors were evaluated in Neuro2A cell line.
    Results
    The results showed that mean particle size of all these nanocomplexes was lower than 266 nm with surface charge of 22.0 to 33.9 mV. Almost the same condensation pattern was observed in all vectors and complete condensation was occurred at C/P ratio of 1.5. The lipoplexes containing modified PAA 15 kDa with 10% hexyl acrylate showed the highest transfection efficacy and lowest cytotoxicity in C/P ratio of 0.5.
    Conclusion
    In some cases nanocomplexes consisting of cationic liposome and modified PAA showed better transfection activity and lower cytotoxicity compared to PAA.
    Keywords: Liposomes, Lipoplexes, Non, viral vector, Polyallylamine, Transfection efficiency
  • Elham Ahmadian, Hossein Babaei, Alireza Mohajjel Nayebi, Aziz Eftekhari, Mohammad Ali Eghbal * Pages 521-530
    Purpose
    Depression is a public disorder worldwide. Despite the widespread use of venlafaxine in the treatment of depression, it has been associated with the incidence of toxicities. Hence, the goal of the current investigation was to evaluate the mechanisms of venlafaxine–induced cell death in the model of the freshly isolated rat hepatocytes.
    Methods
    Collagenase-perfused rat hepatocytes were treated with venlafaxine and other agents. Cell damage, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential decline, lysosomal damage, glutathione (GSH) level were analyzed. Moreover, rat liver mitochondria were isolated through differential centrifugation to assess respiratory chain functionality.
    Results
    Our results demonstrated that venlafaxine could induce ROS formation followed by lipid peroxidation, cellular GSH content depletion, elevated GSSG level, loss of lysosmal membrane integrity, MMP collapse and finally cell death in a concentrationdependent manner. N-acetyl cysteine, taurine and quercetine significantly decreased the aforementioned venlafaxine-induced cellular events. Also, radical scavenger (butylatedhydroxytoluene and α-tocopherol), CYP2E1 inhibitor (4-methylpyrazole), lysosomotropic agents (methylamine and chloroquine), ATP generators (L-gluthamine and fructose) and mitochondrial pore sealing agents (trifluoperazine and L-carnitine) considerably reduced cytotoxicity, ROS generation and lysosomal leakage following venlafaxine treatment. Mitochondrion dysfunction was concomitant with the blockade of the electron transfer complexes II and IV of the mitochondrial respiratory system.
    Conclusion
    Therefore, our data indicate that venlafaxine induces oxidative stress towards hepatocytes and our findings provide evidence to propose that mitochondria and lysosomes are of the primary targets in venlafaxine-mediated cell damage.
    Keywords: Venlafaxine, Cytotoxicity, Mitochondria, Lysosome, Oxidative stress, Antioxidants
  • Yasaman Arjmand Abbassi, Mohammad Taghi Mohammadi *, Mahsa Sarami Foroshani, Javad Raouf Sarshoori Pages 531-539
    Purpose
    Previous findings have shown the crucial roles of brain renin-angiotensin system (RAS) in pathogenesis of Alzheimer’s disease (AD). Since RAS inhibitors may have beneficial effects on dementia and cognitive function in elderly people, the aim of present study was to examine the neuroprotective actions of captopril and valsartan on memory function and neuronal damage in experimental model of AD.
    Methods
    Adult forty male Wistar rats (220-280g) were randomly divided into 5 groups; Control, Vehicle, Alzheimer and treatment groups. AD was induced by the injections of streptozotocin (3mg/kg, bilateral intracerebroventricular) at days 1&3. Treated rats received orally captopril (50mg/kg/day) and valsartan (30mg/kg/day). Memory function and histological assessments were done at termination of experiment. Finally, superoxide dismutase (SOD) and catalase (CAT) activities as well as malondialdehyde (MDA) and NOx contents were determined.
    Results
    There was a significant increase in the mean value of latency in Alzheimer group (66%). Captopril and valsartan considerably decreased this value in both treatment groups (45% and 72%, respectively). In Alzheimer group the activities of brain’s SOD and CAT reduced (40% and 47%, respectively) in accompany with an increase in MDA and NOx contents (49% and 50%, respectively). Captopril and valsartan significantly increased the activities of brain’s SOD and CAT concomitant reduction in MDA and NOx contents. Also, histopathological damages noticeably decreased in both treatment groups.
    Conclusion
    Our findings indicate that RAS inhibition by using captopril and valsartan potentiates the antioxidant defense system of brain and reduces oxidative/nitrosative stress in accompany with neuronal damage during AD.
    Keywords: Alzheimer's disease, Antioxidant, Renin, angiotensin system, Captopril, Valsartan
  • Asma Ravanbakhsh, Majid Mahdavi *, Ghader Jalilzade, Amin, Shahram Javadi, Masoud Maham, Daryosh Mohammadnejad, Mohammad Reza Rashidi * Pages 541-549
    Purpose
    Median septum of Juglans regia L. (Juglandaceae) with anti-diabetic effects has been used in Iranian traditional medicine. The present study estimates both oral acute and subchronic toxicities.
    Methods
    In the oral acute toxicity study, female Wistar rats were treated with doses of 10, 100, 1000, 1600, 2900 and 5000 mg/ kg of the Juglans regia septum of methanol extract (JRSME), and were monitored for 14 days. In subchronic study, JRSME was administered by gavage at dose of 1000 mg/kg daily in Wistar rats for 28 days. Antioxidant status and biochemical examinations were fulfilled, and the vital organs were subjected to pathological analyses.
    Results
    The extract did not produce any toxic signs or deaths; the medium lethal dose must be higher than 5000 mg/kg. In subchronic study, No significant morphological and histopathological changes were observed in the studied tissues. There was a significant increase in serum malondialdehyde (MDA) level in treated group compared to control after 4 weeks of JRSME intake. The treatment of rats resulted in a significant reduction of serum urea level (p
    Conclusion
    This study showed that the extract has no acute or subacute adverse effects with dose of 1000 mg/kg. The administration of JRSME may improve kidney structure and function and help in treatment of some chronic diseases.
    Keywords: Juglans regia, Toxicity, Antioxidant enzymes, Oxidative stress, Wistar rats
  • Azam Safary, Rezvan Moniri *, Maryam Hamzeh, Mivehroud, Siavoush Dastmalchi Pages 551-561
    Purpose
    Robust pharmaceutical and industrial enzymes from extremophile microorganisms are main source of enzymes with tremendous stability under harsh conditions which make them potential tools for commercial and biotechnological applications.
    Methods
    The genome of a Gram-positive halo-thermotolerant Bacillus sp. SL1, new isolate from Saline Lake, was investigated for the presence of genes coding for potentially pharmaceutical enzymes. We determined gene sequences for the enzymes laccase (CotA), lasparaginase (ansA3, ansA1), glutamate-specific endopeptidase (blaSE), l-arabinose isomerase (araA2), endo-1,4-β mannosidase (gmuG), glutaminase (glsA), pectate lyase (pelA), cellulase (bglC1), aldehyde dehydrogenase (ycbD) and allantoinases (pucH) in the genome of Bacillus sp. SL1.
    Results
    Based on the DNA sequence alignment results, six of the studied enzymes of Bacillus sp. SL-1 showed 100% similarity at the nucleotide level to the same genes of B. licheniformis 14580 demonstrating extensive organizational relationship between these two strains. Despite high similarities between the B. licheniformis and Bacillus sp. SL-1 genomes, there are minor differences in the sequences of some enzyme. Approximately 30% of the enzyme sequences revealed more than 99% identity with some variations in nucleotides leading to amino acid substitution in protein sequences.
    Conclusion
    Molecular characterization of this new isolate provides useful information regarding evolutionary relationship between B. subtilis and B. licheniformis species. Since, the most industrial processes are often performed in harsh conditions, enzymes from such halo-thermotolerant bacteria may provide economically and industrially appealing biocatalysts to be used under specific physicochemical situations in medical, pharmaceutical, chemical and other industries.
    Keywords: Molecular characterization, Pharmaceutical enzymes, Gene sequence, Halo, thermo tolerant Bacillus
  • Leila Rahbarnia, Safar Farajnia*, Hossein Babaei, Jafar Majidi, Bahman Akbari, Shiva Ahdi Khosroshahi Pages 563-571
    Purpose
    EGFRvIII as the most common mutant variant of the epidermal growth factor receptor is resulting from deletion of exons 2–7 in the coding sequence and junction of exons 1 and 8 through a novel glycine residue. EGFRvIII is highly expressed in glioblastoma, carcinoma of the breast, ovary, and lung but not in normal cells. The aim of the present study was identification of a novel single chain antibody against EGFRvIII as a promising target for cancer therapy.
    Methods
    In this study, a synthetic peptide corresponding to EGFRvIII protein was used for screening a naive human scFv phage library. A novel five-round selection strategy was used for enrichment of rare specific clones.
    Results
    After five rounds of screening, six positive scFv clones against EGFRvIII were selected using monoclonal phage ELISA, among them, only three clones had expected size in PCR reaction. The specific interaction of two of the scFv clones with EGFRvIII was confirmed by indirect ELISA. One phage clone with higher affinity in scFv ELISA was purified for further analysis. The purity of the produced scFv antibody was confirmed using SDS-PAGE and Western blotting analyses.
    Conclusion
    In the present study, a human anti- EGFRvIII scFv with high affinity was first identified from a scFv phage library. This study can be the groundwork for developing more effective diagnostic and therapeutic agents against EGFRvIII expressing cancers.
    Keywords: Human single chain antibody, Cancer, EGFRvIII, Phage display
  • S., Aacute, Ra C., Oacute, Sta Ferreira, Rodriguesc., Aacute, Ssio Milhomens Rodrigues, Jean Antonio Abraham Gautuz, Magali Glauzer Silva, JosÉ Carlos Cogo, Camila Batista, Silva, Cleiton Pita Dos Santos, Francisco Carlos Groppo, Karina Cogo, MÜller, Yoko Oshima, Franco* Pages 573-579
    Purpose
    The aim of this study was to evaluate the antibothropic and anti-inflammatory properties of J. elliptica.
    Methods
    Phytochemical screening and thin-layer chromatography (TLC) assays were performed on J. elliptica hydroalcoholic extract (TE) in order to observe its main constituents. The antibothropic activity of TE was evaluated by the in vitro neuromuscular blockade caused by Bothrops jararacussu venom (Bjssu), in a mouse phrenic nervediaphragm model (PND). A quantitative histological study was carried out to observe a possible protection of TE against the venom myotoxicity. The anti-inflammatory activity was also evaluated in two models, Bjssu-induced paw edema, and carrageenan-induced neutrophils migration in the peritoneal cavity.
    Results
    TLC analysis revealed several compounds in TE, such as saponins, alkaloids, and phenolic constituents. TE was able to neutralize the blockade and the myotoxicity induced by venom, when it was pre-incubated for 30 min with venom. In addition, it showed antiinflammatory activity, inducing less neutrophils migration and reducing paw edema.
    Conclusion
    J. elliptica showed both antibothropic and anti-inflammatory properties.
    Keywords: Bothrops jararacussu, Edema, Inflammation, Jatropha elliptica, Myonecrosis, Neurotoxicity
  • Lavin Aliasgharlou, Saeed Ghanbarzadeh, Hamideh Azimi, Mohammad Hossein Zarrintan, Hamed Hamishehkar* Pages 581-587
    Purpose
    Hyperpigmentation occurs when melanin is overproduced in certain spots on the skin and is one of the most challenging skin conditions to treat. Although it is usually harmless, for cosmetic reasons, it is dreadfully bothersome to those who undergo it. It was reported that N-acetyl-glucosamine (NAGA) prevents melanin synthesis and alters the expression of numerous genes related to pigmentation. In spite of these advantages, NAGA cannot be employed in topical formulations due to its extremely polar characteristics. Nanoparticles, especially lipid-based ones, have been introduced as an efficient carrier for dermal drug delivery.
    Methods
    The aim of the present study was to load adequate hydrophilic NAGA to the lipophilic nanostructured lipid carriers (NLCs) for potential dermal application.
    Methods
    NAGA-loaded NLCs were formulated, using hot homogenization technique, and the characteristics of the optimized formulation were analyzed by laser light scattering, X-ray diffraction, and scanning electron microscopy methods. Loading capacity percentage and in vitro release study were carried out by applying a validated HPLC method. The optimum formulation was utilized for the in vivo skin lightening evaluations in healthy volunteers.
    Results
    NAGA-loaded NLCs demonstrated promising results (the size of 190 nm, narrow size distribution, loading capacity of 9%, and appropriate NAGA release profile) suitable for dermal delivery. XRD results exhibited a dramatic reduction in the crystalline structure of encapsulated NAGA. Dermoscopy images indicated a considerable decline in melanin distribution pattern in the majority of the cases treated with NAGA-loaded NLCs.
    Conclusion
    Thus, this study has opened new horizons for the potential use of lipid based nanoparticles in the managing of hyperpigmentation.
    Keywords: Nanostructured Lipid Carriers, NLCs, N, acetyl glucosamine, Dermal delivery, Hyperpigmentation
  • Md. Kamal Hossain, Amina Khatun *, Mahmudur Rahman (Md) Nahid Akter, Sadia Afreen Chowdhury, S. M. Mahbubul Alam Pages 589-595
    Purpose
    This project was aimed to determine the effect of concurrent administration of sulfamethoxazole and diclofenac sodium.
    Methods
    Equilibrium dialysis method was adopted to study different protein binding aspects of sulfamethoxazole and diclofenac sodium.
    Results
    Sulfamethoxazole showed two types of association constants; high affinity constant 29.0±0.20×106 M-1 with lower number of binding sites of 0.7±1 and low affinity constant 1.13±0.20×106 M-1 with higher number of binding sites of 3.45±1 at pH 7.4 and 40 °C temperature. Diclofenac sodium showed high affinity constant 33.66±0.20×106 M-1 with lower number of binding sites of 1.01±1 and low affinity constant 1.72±0.20×106 M-1 with higher number of binding sites of 6.40±1 at the same condition. Site specific probe displacement data implied that site-I, warfarin sodium site, was the high affinity site, while site-II, diazepam site, was the low affinity site for these drugs. During concurrent administration, sulfamethoxazole increased the free concentration of diclofenac sodium from 17.5±0.14% to 70.0±0.014% in absence and from 22.5±0.07% to 83.0±0.014% in presence of site-I specific probe. Diclofenac sodium also increased the free concentration of sulfamethoxazole from 2.8±0.07% to 52.0±0.14% and from 8.5±0.014% to 64.4±0.07% in absence and presence of site-I specific probe respectively.
    Conclusions
    The study revealed that the concurrent administration of sulfamethoxazole and diclofenac sodium may result drug concentration alteration in blood.
    Keywords: Bovine serum albumin, Diazepam, Diclofenac sodium, Equilibrium dialysis, Sulfamethoxazole, Warfarin sodium
  • Solmaz Abedinzadeh, Mohammadali Torbati, Sodeif Azadmard, Damirchi Pages 597-606
    Purpose
    Lipid oxidation and rheological properties are the main qualitative parameters determined in food emulsions. Salad dressings are food emulsions important in our daily diet, but conventional salad dressings have high amounts of cholesterol and saturated fatty acids because of egg yolk in their formulations. There are many studies on the modification of salad dressing formulations to replace egg yolk and saturated fats. The present study describes new formulation of salad dressing with olive oil and apple vinegar to produce a functional food product.
    Methods
    This study investigated the qualitative properties, oxidative stability, rheological behavior and microstructure of the salad dressing without egg yolk. Oil-in-water emulsions were prepared with virgin olive oil and apple vinegar stabilized with various percentages of xanthan (T1: 0.25%, T2: 0.5%. T3: 0.75%). Samples were stored at refrigerator for 90 days and experiments were performed at production day and during storage.
    Results
    The obtained results showed that peroxide value was increased for all samples during storage, but it was at an acceptable level. Fatty acid changes were not significant during storage. Droplet size was reduced by increasing xanthan gum. T2 had the best rheological properties during storage. Generally, T2 and T3 had higher scores and were more acceptable in organoleptic assay.
    Conclusion
    Obtained results showed that T2 had suitable qualitative and rheological properties and can be a proper egg yolk free salad dressing to introduce to the market.
    Keywords: Lipid oxidation, Xanthan gum, Rheological behavior, Emulsion stability, Microstructure
  • Maryam Maghsoodi *, Ali Nokhodchi Pages 607-616
    Purpose
    The quasi-emulsion solvent diffusion (QESD) has evolved into an effective technique to manufacture agglomerates of API crystals. Although, the proposed technique showed benefits, such as cost effectiveness, that is considerably sensitive to the choice of a stabilizer, which agonizes from a absence of systemic understanding in this field. In the present study, the combination of different solvents and stabilizers were compared to investigate any connections between the solvents and stabilizers.
    Methods
    Agglomerates of celecoxib were prepared by QESD method using four different stabilizers (Tween 80, HPMC, PVP and SLS) and three different solvents (methyl acetate, ethyl acetate and isopropyl acetate). The solid state of obtained particles was investigated by differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) spectroscopy. The agglomerated were also evaluated in term of production yield, distribution of particles and dissolution behavior.
    Results
    The results showed that the effectiveness of stabilizer in terms of particle size and particle size distribution is specific to each solvent candidate. A stabilizer with a lower HLB value is preferred which actually increased its effectiveness with the solvent candidates with higher lipophilicity. HPMC appeared to be the most versatile stabilizer because it showed a better stabilizing effect compared to other stabilizers in all solvents used.
    Conclusion
    This study demonstrated that the efficiency of stabilizers in forming the celecoxib agglomerates by QESD was influenced by the HLB of the stabilizer and lipophilicity of the solvents.
    Keywords: Spherical crystallization, Celecoxib, Quasi emulsion solvent, diffusion method
  • Hossein Niknahad, Reza Heidari *, Roya Firuzi, Farzaneh Abazari, Maral Ramezani, Negar Azarpira, Massood Hosseinzadeh, Asma Najibi, Arastoo Saeedi Pages 617-625
    Purpose
    Accumulating evidence suggests that drug exposure during a modest inflammation induced by bacterial lipopolysaccharide (LPS) might increase the risk of drug-induced liver injury. The current investigation was designed to test if antimalarial drugs hepatotoxicity is augmented in LPS-treated animals.
    Methods
    Rats were pre-treated with LPS (100 µg/kg, i.p). Afterward, non-hepatotoxic doses of amodiaquine (25, 50 and 100 mg/kg, oral) and chloroquine (25, 50 and 100 mg/kg, oral) were administered.
    Results
    Interestingly, liver injury was evident only in animals treated with both drug and LPS as estimated by pathological changes in serum biochemistry (ALT, AST, LDH, and TNF-α), and liver tissue (severe hepatitis, endotheliitis, and sinusoidal congestion). An increase in liver myeloperoxidase enzyme activity, lipid peroxidation, and protein carbonylation, along with tissue glutathione depletion were also detected in LPS and drug co-treated animals.
    Conclusion
    Antimalarial drugs rendered hepatotoxic in animals undergoing a modest inflammation. These results indicate a synergistic liver injury from co-exposure to antimalarial drugs and inflammation.
    Keywords: Drug, Induced Liver Injury, Hepatotoxicity, Inflammation, Lipopolysaccharide, Malaria
  • Javad Khalili Fard, Hossein Hamzeiy, Mohammadreza Sattari, Mohammad Ali Eghbal * Pages 627-637
    Purpose
    Triptans are the drug category mostly prescribed for abortive treatment of migraine. Most recent cases of liver toxicity induced by triptans have been described, but the mechanisms of liver toxicity of these medications have not been clear.
    Methods
    In the present study, we obtained LC50 using dose-response curve and investigated cell viability, free radical generation, lipid peroxide production, mitochondrial injury, lysosomal membrane damage and the cellular glutathione level as toxicity markers as well as the beneficial effects of taurine and/or N-acetyl cysteine in the sumatriptantreated rat parenchymal hepatocytes using accelerated method of cytotoxicity mechanism screening.
    Results
    It was revealed that liver toxicity induced by sumatriptan in in freshly isolated parenchymal hepatocytes is dose-dependent. Sumatriptan caused significant free radical generation followed by lipid peroxide formation, mitochondrial injury as well as lysosomal damage. Moreover, sumatriptan reduced cellular glutathione content. Taurine and N-acetyl cysteine were able to protect hepatocytes against sumatriptan-induced harmful effects.
    Conclusion
    It is concluded that sumatriptan causes oxidative stress in hepatocytes and the decreased hepatocytes glutathione has a key role in the sumatriptan-induced harmful effects. Also, N-acetyl cysteine and/or taurine could be used as treatments in sumatriptaninduced side effects.
    Keywords: Oxidative Stress, Mitochondria, N, acetyl cysteine, Sumatriptan, Taurine, Toxicit
  • Mitra Niafar, Leili Pourafkari, Saina Aminmozaffari, Nader D. Nader* Pages 639-644
    Pupose: Although there are reports of vitamin D (VitD) insufficiency in immunemediated hypothyroidism, an association between VitD and thyroid-stimulating hormone (TSH) levels has yet to be shown. We aim to examine VitD and TSH levels among postmenopausal women, as both conditions are more prevalent in elderly women.
    Methods
    The clinic records of postmenopausal women during their routine maintenance visits were reviewed. All patients were examined for the symptoms related to thyroid function and osteoporosis. Participants were divided into three subgroups according to their TSH levels (below 4.0 mIU/L). Patient characteristics and VitD levels were compared between these subgroups. Multivariate linear regression model was constructed using serum VitD and serum TSH as the dependent variables to identify factors independently associated with these laboratory values.
    Results
    Two-hundred and nighty nine postmenopausal women were included. Average age was 62.2±7.5 years old. VitD was insufficient (10-30 ng/mL) in 12.0% and deficient (
    Conclusion
    Age was the only independent predictor of serum VitD in this study population. Though suppressed TSH was associated with higher VitD levels, the association was not linear between TSH and VitD in postmenopausal women.
    Keywords: Menopause, Vitamin D, Thyroid stimulating hormone
  • Mostafa Ejtehadifar, Karim Shamsasenjan, Parvin Akbarzadehlaleh*, Sarah Zahedi, Narjes Kazemi Pages 645-650
    Purpose
    Mesenchymal Stem Cells (MSCs) are the most important members of Bone Marrow (BM) milieu. MSCs affect different kinds of cells, particularly malignant cells of hematologic malignancies, but the effects of MSCs are unclear exactly. Here we analyzed the effects of derived Umbilical Cord Blood-MSCs on proliferation, cell death and some surface markers of U937 cell line in a Co-culture system with MSCs.
    Methods
    Here we designed Co-culture systems as a model of BM milieu. We cultured U937 cells on UCB-MSCs and MSCs Conditioned Medium (C.M) driven and then treated U937 cells with optimum concentration of chloride cobalt (CoCl2) as a hypoxia-mimetic agent. In addition, we applied suitable concentrations of H2O2 to induce cell death. Proliferation rate, cell death rate and some surface markers of hypoxic U937 cells were analyzed by MTT assay, flow cytometry and Real Time-PCR were flown respectively.
    Results
    UCB-MSCs showed supportive effects on U937 proliferation rate in normoxia and hypoxia. Lethal effect of H2O2 suppressed in the presence of UCB-MSCs in hypoxia and normoxia. Among CD11a, CD14, CD49d, CD54 and CD116 markers, CD49d was down regulated in presence of UCB-MSCs and CD116 was up regulated in hypoxia. Other markers didn’t show any significant changes.
    Conclusion
    This work provides evidences that MSCs play critical roles in U937 cells biology. These observations shed new light on MSCs roles and demonstrated that MSCs should be regarded as an important member of BM milieu in several clinical applications such as BM transplantation prognosis and treatment of hematologic malignancies.
    Keywords: Hypoxia, Mesenchymal Stem Cells, U937 cell line, Proliferation, CD116, CD49d
  • Sanaz Balkani, Sara Shamekhi, Ramin Raoufinia, Reza Parvan, Jalal Abdolalizadeh* Pages 651-654
    Purpose
    Albumin is an abundant protein of blood and has many biopharmaceutical applications. The aim of this study was to purify bovine serum albumin (BSA) using produced rabbit anti-BSA antibody.
    Methods
    The polyclonal antibody was produced against the BSA in rabbits. Then, the pure BSA was injected to three white New Zealand rabbits. ELISA test was done to evaluate antibody production. After antibody purification,the purified antibody was attached to CNBr-activated sepharose and finally it was used for purification of albumin from bovine serum. Western blotting analysis was used for functional assessment of immunoaffinity purified BSA.
    Results
    The titer of anti-bovine albumin determined by ELISA was obtained 1: 256000. The SDS-PAGE showed up to 98% purity of isolated BSA and western blotting confirmed the BSA functionality. Purified bovine serum albumin by affinity chromatography showed a single band with molecular weight of 66 KDa.
    Conclusion
    Affinity chromatography using produced rabbit anti-BSA antibody would be an economical and safe method for purification of BSA.
    Keywords: Bovine serum albumin (BSA), Chromatography, Immunoaffinity purification, Polyclonal antibody, Western blotting