فهرست مطالب

  • Volume:24 Issue: 4, 2019
  • تاریخ انتشار: 1397/10/23
  • تعداد عناوین: 13
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  • Shabnam Mahernia , Niusha Sharifi , Malihe Hassanzadeh*, Nastaran Rahimi , Nastaran Pourshadi , Arash Amanlou , Ahmad Reza Dehpour , Massoud Amanlou Pages 250-256
    Background
    Barbituric acid derivatives have long been used as central nervous system (CNS) suppressants, such as sedatives, hypnotics and anticonvulsants. In addition, previous studies have implicated the involvement of nitric oxide (NO) in the anticonvulsive effects of barbiturates in CNS. Therefore, the purpose of this study was to figure out the effects of a novel class of barbituric acid derivatives on pentylenetetrazole (PTZ)-induced seizures in male mice.
    Methods
    Thirteen synthesized barbituric acid derivatives (a-m) and phenobarbital were administered intraperitoneally (i.p.) 30 min before induction of seizures by PTZ administration. The mechanisms of PTZ-induced seizures in the mice was evaluated using a non-selective nitric oxide synthase (NOS) inhibitor, selective inducible NOS (iNOS) inhibitor, a selective neuronal NOS (nNOS) inhibitor, and NO substrate.
    Results
    Administration of most of the above mentioned derivatives significantly increased the seizures threshold (P<0.001). The most potent derivative (compound a), was chosen in order to investigate the mechanism of action involving in anticonvulsant activity. Administration of a non-selective NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) and a selective nNOS inhibitor, 7-nitroindazole (7-NI) reversed anticonvulsant activity of compound a. However, injection of the nitric oxide precursor, L-arginine (L-Arg) and a selective iNOS inhibitor, aminoguanidine (AG), did not change anticonvulsant activity of the mentioned compound.
    Conclusion
    These results indicated that the NO system, specifically nNOS may contribute to the anticonvulsant activity of benzylidene barbituric acid derivative a. Therefore, this compound is a good candidate in order to designing new anticonvulsant medications
    Keywords: Barbituric acid, Nitric oxide, Nitric oxide synthase inhibitors, Pentylenetetrazole, Seizure, Mice
  • Aziz Eftekhari , Reza Heidari , Elham Ahmadian , Mohammad Ali Eghbal* Pages 257-263
    Background
    Drug-induced liver injury is a critical clinical complication. Hence, finding new and safe protective agents with potential clinical application is of value. Isoniazid (INH) is an antituberculosis agent widely used against Mycobacterium tuberculosis infection in human. On the other hand, hepatotoxicity is a clinical complication associated with isoniazid therapy. Oxidative stress and its associated events are major mechanisms identified for INH-induced liver injury. Carnosine is an endogenously found peptide widely investigated for its hepatoprotective effects. On the other hand, robust antioxidant and cytoprotective effects have been attributed to this peptide.
    Methods
    The current study designed to evaluate the potential cytoprotective properties of carnosine against INH-induced cytotoxicity in drug-exposed primary cultured rat hepatocytes. Primary cultured rat hepatocytes were incubated with INH (1.2 mM).
    Results
    INH treatment caused significant increase in cell death and lactate dehydrogenase (LDH) release. On the other hand, it was found that markers of oxidative stress including reactive oxygen species were significantly increased in INH-treated cells. Cellular glutathione reservoirs were also depleted in INH-treated group. Carnosine treatment (50 and 100 µM) significantly diminished INH-induced oxidative stress and cytotoxicity.
    Conclusion
    These data mention carnosine as a potential protective agent with therapeutic capability against INH hepatotoxicity.
    Keywords: Cytotoxicity, Drug-induced liver injury, Hepatotoxicity, Mitochondria, Oxidative stress, Antioxidants
  • Mostafa Fallah , Najmeh Moghble , Iraj Javadi , Hossein Bahadoran , Alireza Shahriary* Pages 264-272
    Background
    Arsenic is a toxic element that widely widespread in environment. Inflammation is now considered as one of the major mechanisms implicated in arsenic poisoning. Curcumin (Cur) and N-acetylcysteine (NAC) are potential antioxidants that protect cells against inflammation. This study aimed to compare the protective effect of Cur and NAC on brain histology and inflammatory factors, including matrix metalloproteinases-2, -9 (MMP-2, 9) and tumor necrosis factor-α (TNF-α) in rats exposed to single dose of arsenic.
    Methods
    Rats were exposed to single dose of arsenic (20mg/kg, by gavage) for 30 days and then treated with 300mg/kg NAC (by gavage) and 100mg/kg Cur (by gavage), individually. Serum level of TNF-α was measured using specific ELISA kits. MMP2 and MMP9 contents were measured using Gelatin Zymography method. Brain samples were collected for histopathological and morphological examinations.
    Results
    Arsenic treatment induced white matter lesions and cellular damages at hippocampal CA1 area of the brain. The number of hippocampal CA1 pyramidal cells was significantly declined in arsenic exposed rats (p<0.05). Treatment with NAC and Cur improved these abnormalities. The mean levels of MMP2, MMP9 and TNF-α inflammatory biomarkers were slightly declined after treatment with NAC and Cur (p>0.05).
    Conclusion
    NAC and Cur play an important role in protecting the hippocampal CA1 cells injury induced by arsenic.
    Keywords: Curcumin, inflammation, MMPs, N-acetylcysteine, TNF-?
  • Parivash Piraki , Ahmad Hemmatfar*, Mohammad Ali Samavati Sharif , Naser Behpour Pages 273-279
    Background
    The main purpose of the present study was to assess the effects of exhaustive swimming with the consumption of a vitamin C supplement on indices of myocardial oxidative stress and gene expression related to angiogenesis.
    Methods
    Wistar rats were randomly divided into six groups of normal (C), 100 and 200 mg/kg of vitamin C, (VC100 and VC200), exercise with 100 and 200 mg/kg of vitamin C (Ex+VC100 and Ex+VC200) and exercise without treatment (Ex). Finally, the serum activity of serum creatine phosphokinase (CK) and lactate dehydrogenase (LDH) and heart tissue oxidant/antioxidant parameters, besides gene expression of Vascular endothelial growth factor-B (VEGF-B), angiopoietin 1 (ANGPT-1) and matrix metalloproteinases 2 (MMP-2) was measured.
    Results
    Significant increase in LDH level was seen in group Ex which was remarkably attenuated in group Ex+VC200 (p<0.001). The tissue oxidative stress was observed in group Ex where daily intake of vitamin C could remarkably regulate this property (p<0.01). Vitamin C could ameliorate significant upper gene expression of VEGF-B and MMP-2 remarkably (p<0.05).
    Conclusion
    Oxidative condition in myocardial besides over expression of MMP-2, could be concluded as a detrimental condition resulting from exhaustive swimming that continued by the proteolytic release of CK and LDH from the muscle. Upper gene expression of VEGF-B and MMP-2 besides no changes of ANGPT-1 can be concluded as an early stage of angiogenesis. All these events were somehow attenuated by vitamin C which confirmed its beneficial effects as an antioxidant and the role of oxidation properties in the regulation of angiogenesis.
    Keywords: Exercise Training, Cardiac Function, Oxidative Stress, Ascorbic Acid, Metalloproteinase 2, Vascular Endothelial Growth Factor B
  • Alireza Khodavandi , Fahimeh Alizadeh*, Mahsa Jafarzadeh Pages 280-290
    Background
    Candidiasis has gained much attention in recent decades due to its increasing prevalence in immunocompromised patients. Usually, antifungals such as fluconazole and amphotricin B are used for treatment of candidiasis, but one of the major clinical problems is the emergence of antifungal resistance. Combination antifungal therapy is one of the most commonly used methods to alleviate the problem of antifungal resistance.
    Methods
    The effect of fluconazole alone and in combination with amphotericin B on C. tropicalis isolates were performed using the Clinical and Laboratory Standards Institute (CLSI) reference method. Eventually hypha formation, time kill study, proteinase and phospholipase activity and expression of PLB and SAP2 genes were carried out to investigate the enzymes inhibitory properties of antifungal tested against C. tropicalis.
    Results
    Results showed the significant synergic effect of fluconazole in combination with amphotericin B in inhibiting the growth of C. tropicalis isolates, with fractional inhibitory concentration indices ranging from 0.06 to 0.5. The combination of fluconazole with amphotericin B reduced the number of yeast form and inhibited the yeast to hyphae transition in C. tropicalis. The antifungals tested were able to show the effect of down regulating expression of the selected genes significantly in fluconazole/amphotericin B ranging from 1.42- to 2.27-fold.
    Conclusion
    Our results demonstrated that the synergistic interaction of fluconazole/amphotericin B would be worth exploring for the management of candidiasis. In addition, PLB and SAP2 genes could be probable molecular targets in the synergistic interaction of fluconazole/amphotericin B in C. tropicalis.
    Keywords: Amphotericin B, Candida tropicalis, Fluconazole, PLB, SAP2
  • Geetha Bhavani Koduri , Hari Babu Bollikolla , Ramachandran Dittakavi*, Srinivasu Navuluri * Pages 291-297
    Background
    Pimavanserin, an antipsychotic agent, is used to treat patients suffering with Parkinson's disease. Till now no stability indicating reverse phase HPLC method was reported for the quantification of pimavanserin in bulk and tablet dosage form. Hence in the present study, a new sensitive, precise and accurate stability indicating reverse phase HPLC method with photodiode array detector has been developed for the quantification of pimavanserin in bulk and tablet dosage form.
    Methods
    Separation and analysis of pimavanserin was achieved on Kromasil C18 (5 µm, 250 mm × 4.6 mm) column using 0.1M NaH2PO4, methanol and acetonitrile in ratio of 55:30:15 (v/v/v) as mobile phase at 25°C. The flow rate was 1.0 ml/min. The effluents were monitored with detector set at 239 nm. The method validation was done with regard to the guidelines by the International Conference on Harmonization. Pimavanserin was subjected to acid, alkali and neutral hydrolysis, hydrogen peroxide oxidation, thermal degradation, and photo (sunlight) degradation.
    Results
    Linear relationship was obtained between the concentration of drug and peak area response in the range of 4.25-34.0 µg/ml. The limits of detection and quantitation were found to be 0.027 µg/ml and 0.089 µg/ml, respectively. All the validation characteristics were within the acceptance criteria. The peaks of degradation products were well resolved from the pimavanserin peak.
    Conclusion
    The developed and validated method is able to quantify the pimavanserin in the presence of degradation products.
    Keywords: Pimavanserin, Antipsychotic, Stability Indicating, HPLC, Analysis
  • Hamid Reza Sargazi , Elnaz Tamizi , Elaheh Rahimpour , Abolghasem Jouyban Pages 298-303
    Background
    A micellar electrokinetic chromatographic (MEKC)/ indirect UV detection method with hydrodynamic and electrokinetic injection has been developed for the determination of pregabalin in the serum samples.
    Methods
    Separation of the drug was achieved on Agilent capillary electrophorese in less than 5 min using a 50 cm × 75 μm i.d. uncoated fused-silica capillary and a background electrolyte (BGE) consisting of 5-aminosalicylic acid (5-ASA, 10 mmol L-1), cetyl trimethylammonium bromide (CTAB, 1 mmol L-1) and tri-sodium citrate (4% w/v). The influence of various parameters on the separation such as separation voltage, injection time, cassette temperature, pH of BGE and organic modifier was investigated.
    Results
    Method validation shown good linearity (R2> 0.999) in the range of 1.5-100 µg mL-1 of pregabalin. A limit of detection (LOD) of 0.8 μg mL-1 and a limit of quantitation (LOQ) of 2.6 μg mL-1 were reported for pregabalin.
    Conclusion
    The proposed method was found to be suitable and accurate for the determination of pregabalin in serum samples.
    Keywords: Field-amplified sample injection, Micellar electrokinetic chromatography, Capillary electrophoresis, Pregabalin
  • Dewi Melani Hariyadi*, Noorma Rosita , Fitria Nugrahaeni Pages 304-312
    Background
    The present study aimed to formulate and evaluate the stability, characteristics and effectiveness of glutathione-loaded alginate microspheres through increased lipophilicity using surfactant with a Hydrophylic-Lipophilic Balance (HLB) value equal to 7. The selection of glutathione as an antioxidant was based on its prominent role in maintaining intracellular redox balance. Alginate was used as the polymer, while calcium chloride constituted a cross-linking agent and Tween and Span were employed as surfactants.
    Methods
    The study applied an ionotropic gelation-aerosolization method. Microspheres were characterized by their morphology, size, drug loading, entrapment efficiency and yield. Stress testing utilized a forced degradation method, while an effectiveness study of glutathione incorporated a Matrix Metalloproteinase I (MMP-1) parameter on mouse skin. Glutathione-microspheres, to which had been added surfactants with a HLB value equal to 7, were compared to those without surfactants.
    Results
    Microspheres demonstrated both high yield and encapsulation efficiency. From the stability study conducted, it was evident that the glutathione-microspheres with additional surfactant were more stable than glutathione with surfactant, but without microspheres. Similarly, the glutathione-microspheres with additional surfactant were more stable than the glutathione without surfactant. The in vivo effectivity showed lipophilic glutathione microspheres were able to decrease MMP-1 expression in the dermis tissue of mice.
    Conclusion
    The results of freeze-dried glutathione-loaded alginate microspheres with surfactant with a HLB value equal to 7 can be utilized as potential glutathione delivery systems.
    Keywords: Alginate microspheres, Aerosolization, Glutathione, Surfactants, Mmp-1 expression
  • Robert Tungadi *, Widy Susanty , Prisca Wicita , Elvira Pido Pages 313-323
    Background
    The aim of the present study was to characterize and evaluate the nanoemulgel (NEG) of snakehead fish powder (SFP), as a transdermal delivery system for poorly water soluble drug, in order to conquer the inconveniences related to its oral conveyance.
    Methods
    Diverse nanoemulsion components (oil, surfactant, and co-surfactant) were chosen based on solvency and emulsification capacity. SFP loaded nanoemulsion which tested by stress-stability testing was carried out for all formulations and those that passed these tests were characterized for mean droplet size, polydispersity index (PDI), zeta potential, pH, viscosity, and transmittance. After that, this was continued by permeation studies using snake skin in vitro and rabbit skin in vivo studies i.e. skin irritation study and the effectiveness test.
    Results
    Mean droplet size and zeta potential of the optimized nanoemulsion (NE4) were found to be 98.6 ± 0.93 nm (polydispersity index, PDI = 0.1 ± 0.20) and -57.5 ± 0.3 mV respectively. Optimized nanoemulsion was converted into nanoemulgel with 1.5% w/v of gelling agent (HPMC) and evaluated for pH, viscosity, spreadability, and extrudability measurement. Ex vivo transdermal permeation value for SFP through snake skin as membrane from NEG1, NEG2, NEG3 and marketed SFP cream showed results of 55.65 ± 0.93%, 56.14 ± 0.70%, 66.75 ± 1.03% and 49.80 ± 3.42% respectively in 3 hours. Moreover, all the treatment group did not show skin irritation of each group. The effect of burn wound healing of NEG3 showed a significant (P<0.05) on the measurement of wound area compared to marketed cream.
    Conclusion
    The novel NEG of SFP was successfully formulated for transdermal application based on the results of evaluations and stability tests on accelerating burn wound healing.
    Keywords: burn wound, nanoemulgel, nanoemulsion, snakehead fish powder, transdermal
  • Dario A Tinjaca , Maria M Mu?oz , Fleming Martinez*, Abolghasem Jouyban , William E Acree Jr Pages 324-331
    Background
    Sucrose is the most widely used sweetener in foods and pharmaceuticals. Apparent specific volumes of this excipient in aqueous cosolvent mixtures are not available. Thus, the main objective of this research was to determine this property by measuring the density of several solutions of sucrose in {cosolvent + water} mixtures at 298.2 K.
    Methods
    Sucrose dissolutions were prepared gravimetrically and a thermostatically controlled digital oscillatory method was used to measure the dissolutions density.
    Results
    From density values of sucrose dissolutions and cosolvent mixtures the apparent specific volumes of sucrose were calculated and analyzed based on the sucrose and cosolvent proportions in the mixtures.
    Conclusion
    Useful density values of sucrose solutions at different concentrations in several aqueous cosolvent mixtures are reported at 298.2 K. Finally, a mean apparent specific volume value of 0.632 cm3.g–1 for sucrose in different aqueous-cosolvent mixtures could be adequate for practical purposes in pharmaceutical industries.
    Keywords: Sucrose, Cosolvents, Density, Apparent specific volume
  • Mohammad, Reza Delnavazi , Parisa Saiyarsarai , Saeedeh Jafari, Nodooshan , Mahnaz Khanavi , Saeed Tavakoli , Hormoz Hadavinia , Narguess Yassa* Pages 332-339
    Background
    Stachys lavandulifolia Vahl is a herbaceous plant distributed in the west and south western Asia. Despite of the wide medicinal uses, there are some reports on toxicity potential of this plant. In present study we attempted to evaluate the toxicity and to characterize the cytotoxic principles of S. lavandulifolia.
    Methods
    Brine shrimp lethality test (BSLT) was used to evaluate the general toxicity of the extracts and essential oil obtained from the aerial parts of S. lavandulifolia. Phytochemical constituents of the active extract were investigated using various chromatographic and spectroscopic methods. GC and GC-MS were also used to analyze the plant essential oil. GC and GC-MS were used to analyze the plant essential oil. Cytotoxic activities of the isolated compounds were also evaluated using MTT assay method.
    Results
    In brine shrimp lethality test (BSLT), chloroform extract and the plant essential oil exhibited the most toxicity against Artemia salina larvae (LD50: 121.8±5.6 and 127.6±14.7 µg ml-1, respectively). GC and GC-MS analyses of essential oil led to the characterization of forty compounds of which α-bisabolol (23.85%) and thymol (17.88%) were identified as the main constituents. Nine flavonoids, Pachypodol (1), chrysosplenetin (2), kumatakenin (3), velutin (4), penduletin (5), viscosine (6), chrysoeriol (7), hydroxygenkwanin (8) and apigenin (9) were isolated from the chloroform extract of S. lavandulifolia. Among the isolated compounds, chrysosplenetin (2), a polymethoxylated flavonoid, was found as the most toxic compound toward MDA-MB-23 and HT-29 cells, with IC50 values of 88.23 and 116.50 µg ml-1, respectively. Furthermore, chrysosplenetin (2), kumatakenin (3) and viscosine (6) with selectivity indices of 2.70, 2.59 and 3.33, respectively, showed higher preferential toxicity against MDA-MB-23 cells in comparison with tamoxifen (SI:2.45).
    Conclusion
    This study reports methoxylated flavonoids as compounds which could be involved in toxicity of S. lavandulifolia. The results of MTT assay also suggest some of these compounds as appropriate candidates for anti-cancer drug development research.
    Keywords: Stachys lavandulifolia Vahl, Toxicity, Essential oil, flavonoid, Brine shrimp lethality test, MTT assay
  • Peyman Amini , Saeed Rezapoor , Dheyauldeen Shabeeb , Ahmed Eleojo Musa , Masoud Najafi*, Elahe Motevaseli* Pages 340-345
    Background
    Epidemiological studies have shown an increased incidence of heart diseases among survivors of Chernobyl disaster as well as Hiroshima and Nagasaki atomic bomb explosion. Similar results were observed for lung and left breast cancer patients. Experimental studies have proposed the chronic upregulation of some pro-inflammatory and pro-fibrotic cytokines. Recent studies have shown that upregulation of pro-oxidant enzymes play a key role in the development of late effects of ionizing radiation such as fibrosis. Interleukin-4 (IL-4) and Interleukin-13 (IL-13) are two important cytokines that have shown ability to induce production of free radicals through dual oxidases (Duox) i.e. Duox1 and Duox2. In this study, we aimed to detect the expression of IL-4 receptor-a1 (IL-4Ra1), IL-13 receptor-a2 (IL-13Ra2), Duox1 and Duox2 genes following irradiation of rat’s heart. In addition, we evaluated the possible role of the combination of curcumin and selenium-L-methionine on the regulation of these genes.
    Methods
    Twenty rats were divided into 4 groups as follows; G1: control; G2: treatment with the combination of curcumin and selenium-L-methionine; G3: radiation; G4: radiation plus treatment with the combination of curcumin and selenium-L-methionine. Rats were sacrificed 10 weeks after irradiation for detecting the expression of IL-4Ra1, IL-13Ra2, Duox1 and Duox2.
    Results
    Results showed that exposure to ionizing radiation caused upregulation of IL-4Ra1 by more than 4-fold as well as Duox1 and Duox2 by more than 5-fold. However, results showed no detectable expression for IL-13Ra2. Treatment with the combination of curcumin and selenium-L-methionine could attenuate the upregulation of all genes.
    Conclusion
    This study has shown that exposing rat’s heart tissues to radiation leads to chronic upregulation of IL-4Ra1, Duox1 and Duox2 as well as pro-oxidant enzymes. Treatment with the combination of curcumin and selenium-L-methionine showed ability to attenuate the upregulation of these genes.
    Keywords: Curcumin, Selenium-L-Methionine, Radiation, Dual Oxidase
  • Ali Shayanfar , Sanaz Hamedeyazdan , Alireza Garjani * Page 346
    The editors of Pharmaceutical Sciences would like to thank all of our reviewers and particularly our top reviewers who have contributed to the journal in Volume 24 (2018)
    Keywords: Reviewer, Acknowledgement, Manuscript