PHARMACEUTICAL SCIENCES
Year:2018 | Volume:24 | Issue:3|Papers Count:12

Background: The liver is vulnerable to the toxicity induced by xenobiotics. On the other hand, it has been found that several endogenously-found amino acids have hepatoprotective properties. The current study was designed to evaluate the effect of taurine, glycine, and histidine on the liver function in an ex vivo model of prolonged organ perfusion. Methods: Rat liver was isolated and perfused with a hemoglobin-and albumin-free Krebs-Henseleit buffer (KBH). Liver injury biomarkers were monitored at scheduled time intervals. Results: The perfusate level of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the potassium ion (K + ) were gradually increased in control (Only KBH) group. The histopathological evaluation also revealed significant necrosis, sinusoidal dilation, and pyknosis in control liver. Moreover, significant increase in lipid peroxidation and depletion of hepatic glutathione stores were detected in the control group. It was found that taurine (5, 10 and 20 mM) and glycine (5, 10 and 20 mM)-containing KBH buffer significantly decreased the perfusate level of liver injury biomarkers. Furthermore, lower liver tissue pathological changes, decreased lipid peroxidation, and higher glutathione content was detected in amino acid-treated groups. Histidine administration showed no significant protective effect on liver injury in the current study. On the other hand, combination amino acid administration (glycine and taurine) showed a better hepatoprotective profile. Conclusion: The data obtained from the current study might help to provide safe hepatoprotective agents against xenobiotics-induced hepatotoxicity or preserve liver functionality outside the body.

Background: The aging process is accompanied by low secretion of sex hormones and testicular apoptosis. The antioxidant properties of thymoquinone (TQ) may prevent the effects of aging. Therefore, in the present study, the effects of different doses of TQ were investigated on sperm parameters, testosterone level, apoptosis, and oxidative stress in a mouse model of D-galactose-induced aging. Methods: In this experimental study, 30 adult male mice were randomly divided into 5 groups. The control group did not receive any injections, while the D-galactose group received an intraperitoneal injection of 300 mg/kg of D-galactose for 42 days. The TQ1TQ3 groups received intraperitoneal injections of 5, 2. 5, and 1. 25 mg/kg of TQ plus Dgalactose, respectively for 14 days (from the 1 st to the 14 th day of the experiment). The morphometric analysis, testicular apoptosis examination, and sperm analysis were performed, and testosterone level, total antioxidant capacity, and malondialdehyde level were evaluated on day 42 of the experiment. Data were analyzed using SPSS. Results: Administration of TQ in the TQ1 group caused a significant difference in sperm parameters, compared to the D-galactose group (P<0. 05). The lowest amount of positive tunnel cells was related to 5 mg/kg of TQ and the highest to 2. 5 mg/kg of TQ. There was no significant difference in the parameters of seminal vesicles, epididymis, prostate, and testis between the groups (P>0. 05). The malondialdehyde level were decreased in the TQ1TQ3 groups, compared to the D-galactose group (P<0. 001). On the other hand, the total antioxidant capacity was increased significantly in the TQ1 group, compared to the Dgalactose group (P<0. 001). Conclusion: Administration of 5 mg of TQ for 14 days improved sperm quality and biochemical parameters, while reducing apoptotic cells of the testes in a mouse model of aging.

Background: Due to the antioxidant effects of Zataria multiflora (ZM) and Carvacrol (CAR) in various problems and the prominent role of the ROS in neurotoxicity induced by Doxorubicin (DOX), this study was designed to investigate the effects of ZM hydroalcoholic extract and CAR on DOX-induced oxidative stress in rat brain Methods: 24 male rats were randomly divided into four groups including: 1)Control, 2)Doxorubicin (DOX) that received DOX via a tail vein on the first day of the study, 3, 4) ZM+DOX and CAR+DOX which received ZM and CAR by gavage for 28 consecutive days. Brain tissue removed for redox markers evaluation. Results: MDA level in the DOX group was significantly increased compared to control group while in treated groups did not show any significant changes in comparison with the DOX group. Also, Thiol content in DOX group showed significant reduction compared to control group. Thiol contents in treated groups showed no significant difference compared to DOX group. Catalase (CAT) activity, an antioxidant enzyme, in the DOX group were significantly decreased compared to control group and increased in treated rats in comparison with the DOX group. Activity of Superoxide dismutase (SOD), an antioxidant enzyme, in the DOX group was significantly reduced compared to control group and increased in treated rats in comparison with the DOX group. Conclusion: The present study showed that ZM hydroalcoholic extract and CAR could inhibit DOX induced oxidative stress of the brain mainly with effect on the enzymatic antioxidant defense system.

Background: Attention deficit hyperactivity disorder (ADHD) is a behavioral disorder. The exact pathophysiology of ADHD is not completely recognized. Previous studies have shown the role of different genetic and environmental factors in it. This study investigates the relationship between vitamin D and environmental factors in ADHD. Methods: In this study, 182 children from 2 to 18 years with confirmed ADHD were allocated in this cross-sectional study. Patients with a history of any chronic disease, anticonvulsants and corticosteroids consumption were excluded from the study. The ADHD severity was assessed by Conners’ parent scale test. The level of serum vitamin D, ferritin, iron, total iron binding capacity, zinc, magnesium, calcium and routine complete blood count (CBC) were measured. Results: Although the results showed a U shaped pattern between vitamin D levels and ADHD severity, the correlation between vitamin D level did not show any significant relation with ADHD symptoms severity (p=0. 786). Our data showed significant relation between level of vitamin D and ferritin in patients with ADHD (p=0. 003). The analysis demonstrates significant relation between vitamin D level and duration of daily TV watching in children with ADHD (p=0. 002). Conclusion: The vitamin D supplementation may improve ADHD symptoms in patients with vitamin D deficiency. In addition, due to the proved effect of ferritin level in ADHD and significant relation with vitamin D level in this study, treatment of vitamin D deficiency is necessary in children with ADHD. Replacing TV watching by more outdoor activity may improve ADHD symptoms.

Background: Nymphaea spp., Thai water lilies are aquatic plants. They contain phenolic pigments that play a major role in free radical scavenging. Melanoma is strong aggressive skin cancer-associated with oxidative stress. This study, to determine the effect of Nymphaea spp. extracts on cell apoptosis, cellular migration and invasion through the role of cellular oxidants in B16 melanoma cells. Methods: Free radical scavenging activity and total phenolic were investigated by 1, 1-diphenyl-2 picrylhydrazyl (DPPH) and Ferric reducing anti-oxidant power (FRAP) methods and Folin-Denis test, respectively. Cytotoxic were assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method. Cell apoptosis was confirmed by flow cytometry. Cellular oxidants, cellular migration and invasion were determined with 2, 7-dichlorodihydrofluorescein diacetate (DCFH-DA), wound healing and Boyden chamber assay, respectively. Results: Nymphaea pubescens showed higher capacity of scavenging free radical activity than Nymphaea stellate and also related phenolic content. Nymphaea pubescens extract was toxic to B16 melanoma cells. High concentrations cell apoptosis was induced. Contrastingly, low concentrations showed a decrease in cellular oxidants associated with the suppression of cancer cell progression. In B16 melanoma cell, Nymphaea pubescens extract was able to inhibit B16 melanoma cell migration and invasion through the low doses. Interestingly, the high doses of extract showed a potential of cytotoxicity to induce melanoma cell death. At the low doses, Nymphaea pubescens extract might suppress melanoma cells progression by interfering with both cellular migration and invasion capacity. Conclusion: Hence, Nymphaea pubescens extract induced cellular apoptosis and it also suppressed cancer cell progression by reducing oxidative stress in B16 melanoma cells.

Background: Monoclonal antibodies (mAbs) are considered the most important and financially successful category of the biopharmaceuticals. Extensive optimization of the expression vector, host system and culture parameters are required for the successful production of active monoclonal antibodies in mammalian cells. In this regards, transient expression enables rapid and cost-effective production of recombinant proteins for initial characterization. Methods: In the present study, an internal ribosome entry site (IRES) based bicistronic expression system has been evaluated for the transient expression of an anti-CD52 monoclonal antibody in mammalian cells. The IRES based bicistronic vector was generated through sequential cloning of the Light chain (LC), IRES, and Heavy chain (HC) in an intermediate vector and transfer of the resulting fragment to the expression vector. Transfection of the HEK293T cells was performed and antibody expression was analyzed in cell culture supernatant. Results: Restriction enzyme analysis indicated successful cloning of the antibody coding unit in the expression vector. Analysis of EGFP expression indicated successful transfection of the HEK293T cells. Production levels of 220 μ g/L of antibody were achieved in HEK293T cells during three days of culture. Conclusion: Our results show the convenience and efficiency of the bicistronic expression system for transient expression of the whole monoclonal antibodies in mammalian cells.

Background: Recently, nanotechnology has been demonstrated to be a promising application to overcome the problem of antibiotic resistance. In the present study, we aimed to determine the antibacterial activity of copper oxide nanoparticles (CuO NPs) on several multiple-drug resistant (MDR) uropathogenic strains. Methods: This in vitro case-control study was performed on 4 uropathogenic bacteria including Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa. The antibacterial property was evaluated by well diffusion method at different concentrations of CuO NPs. Results: Overall, NPs concentration of 10, 25 and 50 μ g/mL showed the remarkable antibacterial activity. A lower effect was seen against S. aureus strains. CuO NPs exhibited maximum bacterial growth inhibition against E. faecalis strains. In most of the cases, the zone of inhibition in 50 μ g/mL concentration was closest to control positive antibiotics. Conclusion: In summary, CuO NPs as an alternative to conventional antibiotics that are currently used showed dose-dependent on antibacterial activity against different uropathogens, specificity towards pathogenic Gram-positive bacteria. This promising antibacterial activity of CuO NPs suggesting the development of NPs coatings on the different surface of biomedical materials for applications in different antimicrobial control systems.

Background: Respiratory fungal diseases therapy is still facing challenges as a result of increasing autoimmune disorders, cancers, and immunosuppressive medication usage. Fluconazole is a wide spectrum antifungal agent and is still used successfully in the treatment of opportunistic infections in combination with other antifungal agents. Since, the treatment of respiratory fungal diseases requires prolonged hospitalization; it may increase the chances of other opportunistic infections. Considering the reported drug resistance and adverse effects of systemic administration, it appears that localized pulmonary antifungal therapy may be a suitable alternative route. According to the reported suitable inhalation properties of spray dried powders; spray drying technique was used to prepare fluconazole powders. Methods: Different spray drying parameters such as inlet temperature, pump rate, aspiration%, solvent type, as well as fluconazole concentration were evaluated for powder production. The optimized formulations were characterized using scanning electron microscopy (SEM), x-ray diffraction (XRD), differential scanning calorimetry (DSC) and aerodynamic parameters. Results: All selected formulations showed a smooth surface with similar mass median aerodynamic diameter (MMAD) in a respiratory acceptable range. While optimized powder showed a lower geometric standard deviation (GSD) of 1. 5 with higher fine particle fraction (FPF) of 26% and almost complete deposition recovery of 97%. Conclusion: Based on in vitro characterization results, it appears that spray drying is an appropriate and cost-effective technique for the production of inhalable fluconazole powder. It is characterized by a narrower size distribution and delivers a higher dose which may be more cost effective for mass production.

Background: Antacids are the most commonly used medications for fast symptomatic relief of gastric disorders. Because of adverse effects, low efficiency and the high cost of some chemical antacids, identifying a natural medicine with high efficiency and low cost seems useful. Therefore, the aim of the present study was to prepare antacid tablets from Cuttlefish bone and assessment of its antacid properties. Methods: 24 different formulations of cuttlefish bone were prepared by direct compression using different fillers (starch, cellulose, lactose, and mixture of those) in different ratios of the drug. Characterization of powders and tablets was done on all formulations and marketed dosage forms (calcium carbonate and Al-Mg). Results: Weight uniformity, hardness, and friability of all formulations were in acceptable range. Tablets prepared by calcined cuttlebone disintegrated in longer time due to their higher hardness which were mostly higher than 5 Kg. Also, disintegration time of formulations 50-50 (lower dose of cuttlebone) was less than other tablets (2 minutes or less). Results of antacid capacity showed that formulations 90-10 and 80-20 raise the acidic pH of the medium above 7. 5, which were the same as or more than the capacity of the marketed tablets. Conclusion: Tablets were prepared by 90 or 80% of either calcined or non-calcined cuttlebone showed the highest antacid capacity.

Background: In the current study, simultaneous extraction and concentration of the analytes from the headspace on the solid phase microextraction (SPME) fiber were followed by transferring the essential oil components of Salvia hydrangea DC to the headspace with the help of a heating source. Methods: The essential oil components of the plant were extracted and concentrated in a single step. A one-at-the-time optimization procedure was applied to the microextraction conditions by using the nanocomposite fiber of polypyrrole/SBA-15. Results: The results of the essential oil extraction of Salvia hydrangea clearly demonstrated that polypyrrole/SBA-15 fibers were efficient with SPME technique. The acceptable SPME precision in our study was corroborated by the relative standard deviation (RSD) values of less than 15%. Conclusion: In comparison to the hydro-distillation (HD) method, the SPME technique could equally provide monitoring of almost all the constituents of the studied essential oil in an easier way and shorter time with much lower amounts of the plant sample. The results of the essential oil extraction of Salvia hydrangea clearly demonstrated that polypyrrole/SBA-15 fibers were efficient with SPME technique.

Background: Over the past decade, most antibiotic research programs have focused on finding new compounds with antimicrobial activity. This study aims to investigate the chemical composition and antibacterial activity of the essential oil (EO) extracted from ripe berries of Algerian Juniperus thurifera var. aurasiaca. Methods: The chemical composition of J. thurifera EO extracted by hydrodistillation was analyzed by using the GC-MS technique. Antibacterial activity of EO alone and in combination with three conventional antibiotics was assessed by using disc diffusion method against four bacterial strains. Results: Thirty-five components were identified, representing ~87 % of the oil. The main components were m-mentha-6, 8-diene (15. 43 %), β-pinene (10. 59 %), elemol (8. 31 %) and terpinene-4-ol (7. 44 %). The essential oil showed strong antibacterial activity against S. aureus and E. coli, but no activity against P. aeruginosa and B. subtilis. Synergistic effects were observed because of the combined application of EO with gentamicin against all strains tested, and with amoxicillin against B. subtilis. Furthermore, the combination of EO/cefazolin demonstrated an additive effect against B. subtilis. In contrast, the combination of EO with amoxicillin and cé fazoline revealed antagonistic effects against S. aureus, E. coli, and P. aeruginosa. Conclusion: This is the first report on the chemical composition and antibacterial activity of Algerian juniper berries’ essential oil. The results indicate that the studied EO may be a promising source of antibacterial compounds that could be useful for pharmaceutical applications especially in combination with conventional antibiotics.

Background: Lepidium vesicarium (Cruciferae), one of the important medicinal plants with a long history of medicinal use. The current study was designed to evaluate the free radical scavenging and antimicrobial activities of the L. vesicarium EO as one of the Iranian plant species. Methods: The compositions of the EO from the aerial parts of L. vesicarium were analyzed by GC-MS and GC-FID. Furthermore, anti-oxidant and anti-microbial potentials were investigated via DPPH reagent and disk diffusion procedure, respectively. Results: A total of 18 compounds amounting 97. 70% of the oil have been identified, while Benzyl cyanide (43. 94%), Isothio cyanic acid (22. 69%) and Benzyl isothio cyanate (20. 69%) were the main constituents. The EO showed no activity against the free radicals and studied microbial strains (gram positive and gram negative and also fungi species). Conclusion: On the whole, the presence of cyanide derivatives in studied EO revealed the rational use of this plant in medicine. Comparing with other genesis of Lepidium, anti-oxidant and anti-microbial properties of L. vesicarium essential oil were not noticeable.