فهرست مطالب

Pharmaceutical Sciences - Volume:25 Issue: 1, Mar 2019

Pharmaceutical Sciences
Volume:25 Issue: 1, Mar 2019

  • تاریخ انتشار: 1398/01/28
  • تعداد عناوین: 12
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  • Reza Heidari*, Mohammad Reza Arabnezhad, Mohammad Mehdi Ommati, Negar Azarpira, Elham Ghodsimanesh, Hossein Niknahad Pages 1-10
    Background
    The xenobiotics-induced liver injury is a clinical complication. Hence, finding new hepatoprotective strategies has clinical value. Oxidative stress and its subsequent complications are major mechanisms involved in xenobiotics-induced hepatotoxicity. Boldine is one of the most potent antioxidant molecules widely investigated for its protective properties in different experimental models. In the current study, the hepatoprotective properties of boldine and its potential mechanisms of hepatoprotection have been investigated.
    Methods
    Rats received thioacetamide (TAA; 200 mg/kg, i.p) as a model of acute liver injury. Boldine (5, 10, 1nd 20 mg/kg; 24 hours intervals; oral) was administered as the hepatoprotective agent.
    Results
    Liver injury was evident in TAA-treated animals (48 hours after TAA exposure) as a severe increase in serum level of liver injury biomarkers and histopathological alterations. Moreover, markers of oxidative stress were increased in liver tissue of TAA-treated rats. Assessment of mitochondrial indices of functionality revealed a significant decrease in mitochondrial dehydrogenases activity, the collapse of mitochondrial membrane potential, mitochondrial swelling and depletion of ATP content. It was found that boldine supplementation mitigated liver tissue markers of oxidative stress and improved mitochondrial indices of functionality in TAA-treated animals.
    Conclusion
    The hepatoprotective properties of boldine might primarily rely on antioxidant and mitochondria protecting effects of this alkaloid.
    Keywords: Alkaloid, Bioenergetics, Hepatoprotection, Liver failure, Nutraceuticals, Oxidative stress
  • Saeedeh Shariati , Mohammad Javad Khodayar *, Aliasghar Hemmati , Mehdi Goudarzi , Milad Kiani , Anahita Rezaei Pages 11-16
    Background
    Pulmonary fibrosis is described as a chronic idiopathic inflammatory disease of the interstitial lungs. It is associated with a potentially fatal prognosis, and patients show insignificant response to treatment. To treat paraquat (PQ)-induced pulmonary injury and fibrosis, multiple approaches have been used. We aimed to determine the effects of allopurinol (Allo), a xanthine oxidase inhibitor, on PQ-induced pulmonary fibrosis in rats.
    Methods
    A total of 30 female Sprague-Dawley rats were divided randomly into five groups (200±20 g). Group 1 (control) and group 2 (PQ group) were intraperitoneally administered PQ (20 mg/kg) once on day seven without any treatment, while groups 3–5 orally received 50, 100, and 200 mg/kg of Allo seven days before and three weeks following the administration of PQ, respectively. The animals were sacrificed three weeks after PQ administration. For the histopathological analysis and assessment of serum malondialdehyde (MDA) and hydroxyproline (HP) contents, the animals’ blood and lungs were collected.
    Results
    The PQ group showed significantly higher lung HP, serum MDA, and lung index in comparison with the control. Treatment with Allo, especially at 100 and 200 mg/kg, decreased HP, MDA, and lung index significantly, compared to the PQ group. Allo could prevent inflammatory cell infiltration, presence of fibroblasts, and PQ-related alveolar thickening.
    Conclusion
    The results revealed that Allo has potential protective effects on PQ-related pulmonary fibrosis, and the role of xanthine oxidase in the exacerbation of PQ-induced pulmonary fibrosis was confirmed.
    Keywords: Paraquat, Pulmonary fibrosis, Allopurinol, Antifibrotic, Rats
  • Alireza Parvizpur , Kosar Parnian , Sama Samankan , Fatemeh Fathiazad , Mohammad Charkhpour * Pages 17-23
    Background
    Long-term exposure to opioids may lead to physical dependence and tolerance. The purpose of this study was to investigate the effects of Citrus aurantium essential oil (CEO) on the morphine-induced tolerance and dependence.
    Methods
    To evaluate morphine tolerance, the experiments were carried out in 6 rat groups (n=8) in the weight range of 225-275 g. The control group received morphine (10 mg/kg/day) and the test groups received morphine with the different doses of essential oil (CEO 20, 40 and 80 mg/kg/day) or 4 mL/kg of essential oil vehicle (KolliphorÒ HS15 30% in normal saline that adjusted in pH=7.4 with phosphate buffer) intraperitoneally. The hot-plate test was carried out every other day, 90 minutes after the injections. To examine morphine withdrawal, male Wistar rats were divided into seven groups (n=8) randomly, including: morphine sulphate, CEO (20, 40 and 80 mg/kg) + morphine, vehicle of CEO + morphine. The rats were rendered morphine-dependent by injection of additive doses of morphine subcutaneously for 9 days. The procedure of the morphine administration was as following protocol: day1: 5 mg/kg/12h, day 2 and 3: 10 mg/kg/12h, day 4 and 5: 15 mg/kg/12h, day 6 and 7: 20 mg/kg/12h and day 8 and 9: 25 mg/kg/12h. In the 9th day, 2 hours after the last dose of morphine, naloxone (4 mg/kg) was injected intraperitoneally. Some withdrawal behaviors were counted for 60 minutes.
    Results
    Morphine tolerance was completed after 5 days in the control group. The vehicle group showed tolerance on the 9th day (p-value=0.991), 20mg group in the 13th day (p-value to control=0.010, to vehicle=0.049), 40 mg group on the 15th day (p-value to control and vehicle<0.001) and 80 mg group on the 13th day (p-value to control= 0.001, to vehicle= 0.007). The results showed that CEO could reduce the morphine withdrawal syndrome and total withdrawal score (TWS). Intraperitoneally injection of CEO in two doses (40 mg/kg with p<0.001 and 80 mg/kg with p<0.01) significantly reduced the TWS in comparison to the morphine+vehicle treated group.
    Conclusion
    The results indicated that chronic administration of C. aurantium essential oil extracted had beneficial effects in reducing morphine withdrawal syndrome and could significantly delay tolerance to morphine.
    Keywords: Morphine, Dependence, Tolerance, Withdrawal, Citrus aurantium
  • Hojat Norasteh , Shabnam Mohammadi *, Mohammad Reza Nikravesh , Samaneh Broumand , Farimah Beheshti Pages 24-30
    Background
    Some plants stimulate spermatogenesis and increase fertility, while some cause spermatogenesis arrest. So far, the effects of bene (Pistacia atlantica) on male fertility have not been studied. The aim of this study was to investigate the effects of bene on sperm parameters, testicular histopathology, sperm quality, and oxidative stress in busulfan-induced infertile mice.
    Methods
    Thirty-five male BALB/c mice were randomly assigned to control, sham, busulfan, bene, and bene + busulfan groups. The busulfan group received 10 mg/kg as a single dose and intraperitoneally. The bene group received pellets containing 10% of bene. Another group received 10 mg/kg busulfan and was fed with pellet containing 10% bene. Then, sperms, sperm chromatin quality, testicular histopathology, and oxidative stress levels were studied on the 35th day of the experiment.
    Results
    Busulfan injection resulted in a significant reduction in sperm parameters compared to the control group (p<0.001); it decreased after bene administration (p<0.001). In addition, in the group treated with bene, the sperm count with damaged DNA was reduced and the level of malondialdehyde decreased compared to the busulfan group. A significant increase was observed in the mean level of superoxide dismutase and catalase enzymes in the bene + busulfan group compared to the busulfan group (p<0.001). The histopathological improvement of the testis was observed in the bene + busulfan group.
    Conclusion
    The administration of 10 mg/kg of bene powder for 35 days reduced the oxidative stress, improved testicular histopathology, sperm chromatin quality, and sperm parameters in the infertile mice model.
    Keywords: Bene, Mice, Spermatozoa, Testis
  • Sevda Saleh, Ghadimi, Hamed Jafari, Vayghan , Sorayya Kheirouri , Mohammad Alizadeh * Pages 31-36
    Background
    This study was designed to discover if hydroxymethylfurfural (HMF) exposure modifies cell proliferation and DNA damage in BALB/c mice splenocytes.
    Methods
    Mitogenesis in T cells and B cells was induced by Concanavalin A (Con A) and lipopolysaccharide (LPS). The colorimetric tetrazolium assay was used to evaluate cell proliferation. DNA damaging consequences were evaluated via measurement of 8-hydroxy-2-deoxyguanosine (8-OHdG) level in BALB/c mice splenocytes.
    Results
    Spleen cells proliferation elicited by ConA, was dramatically suppressed by 25, 50 and 100 mM of HMF. However, there was not any significant difference between various concentrations of HMF. The same result was observed following treatment with LPS and HMF in different concentrations. Eight-OHdG concentration was elevated significantly in HMF treated groups compared with untreated control and mitogens.
    Conclusion
    HMF was found to have immunosuppressing and DNA damaging properties in mM concentrations in mice splenocytes.
    Keywords: DNA damage, Hydroxymethylfurfural, Mutagenicity, Splenocyte
  • Korosh Khanaki, Mahmood Abedinzade, Masoud Hamidi * Pages 37-43
    Background
    Diabetes seems to be associated with increased inflammation and induced apoptosis in several tissues. Urtica dioica and Lamium album have shown to possess a variety of beneficial properties like anti-inflammatory effects. In this experimental study, we tried to evaluate the effects of U. dioica and L. album extracts on the expression level of cyclooxygenase-2 (COX-2; as an inflammation marker) and caspase-3 (CASP-3; as an apoptotic marker) in the liver and kidney tissues of diabetic rats.
    Methods
    Thirty-two male Wistar rats were randomly allocated to four groups: normal control, diabetic control, diabetic treated with U. dioica (100 mg/kg/daily), and diabetic treated with L. album (100 mg/kg/daily) for 28 days. At the end of the study, liver and kidney tissues were harvested and mRNA expression level of COX-2 and CASP-3 was determined by real-time PCR technique. Also, serum glucose was measured.
    Results
    Liver COX-2 mRNA in diabetic rats was significantly higher than normal control rats (P=0.02). However, U. dioica and L. album caused significant decrease in mRNA expression of liver COX-2 in diabetic rats (P=0.015 and P=0.03, respectively). Also, in diabetic rats treated with both extracts, serum glucose was remarkably lower than diabetic control rats (P<0.0001 and P<0.01, respectively).
    Conclusion
    It appears that U. dioica and L. album might decrease liver damage by decreasing the inflammatory effects of COX-2 in streptozocin-induced diabetic rats. Since these plant extracts may influence diabetes by several mechanisms, further research in this field is warranted.
    Keywords: Caspase-3 (CASP-3), Cyclooxygenase-2 (COX-2), Diabetes, Lamium album, Urtica dioica
  • Amir Akbari, Rita Arabsolghar *, Abbas Behzad Behbahani, Gholamreza Rafiei Dehbidi, Farahnaz Zare, Mahdieh Hadi Pages 44-49
    Background
    Selective therapy has always been the main challenge in cancer treatments. Recently, it has been shown that Human Gyrovirus-derived protein apoptin (HGV-Apoptin) has selective cytotoxic effects on cancer cells similar to its homologue, Chicken Anemia Virus-derived Apoptin (CAV-Apoptin). However, apoptotic effects of Human Gyrovirus apoptin have been only evaluated on a few cancerous cell lines and need to be further investigated. In this study, we have evaluated the apoptotic effects of HGV-Apoptin and CAV-Apoptin expression on lung cancer (A549) and normal (HEK-293) cell lines, in order to provide more information about the specificity of these proteins on cancerous cells.
    Methods
    Target cells were transfected by the calcium-phosphate precipitation method with constructed plasmids expressing HGV-Apoptin and CAV-Apoptin proteins as well as the control plasmid. Transfection efficiency was followed and imaged by fluorescence microscopy. Quantification of apoptosis was performed by flow cytometry. Measurements were compared by paired Student t-test.
    Results
    Cells were successfully transfected with control and constructed plasmids. Flowcytometry analysis showed that A549 cells transfected with HGV-Apoptin and CAV-Apoptin expressing plasmids, undergone the apoptosis compared to A549 cells transfected with control plasmid (P<0.001). None of the plasmids could induce apoptosis in HEK-293 cells.
    Conclusion
    Human Gyrovirus-derived apoptin (HGV-Apoptin) similar to its homologue, chicken anemia virus derived Apoptin (CAV-Apoptin) can induce apoptosis in Non-small-cell lung carcinoma cell line A549, but not in normal human embryonic kidney cell line HEK-293, which can be introduced as a promising novel specific antitumor agent.
    Keywords: Apoptin, Human gyrovirus, Apoptosis, Tumor specificity, Cancer therapy
  • Fariba Pourkarim , Elaheh Rahimpour , Maryam Khoubnasabjafari , Vahid Jouyban, Gharamaleki , Abolghasem Jouyban * Pages 50-56
    Background
    In this research, an enhanced fluorimetric assay was developed for the direct monitoring of verapamil in exhaled breath condensate (EBC). The method is based on a binding–induced rigidity inside the sodium dodecyl sulfate (SDS) micelle which eliminate collisional quenching and vibrational modes responsible for non-radiative decay. This process produces an enhancement in the emission intensity of verapamil.
    Methods
    Fluorescence intensity measurements were made at 15 ˚C on a FP-750 spectrofluorometer with maximum excitation and emission wavelengths of 280 nm and 310 nm, respectively. The important parameters influencing the analytical signal in experimental steps were investigated and optimized. The method was validated with considering of the linearity, recovery and limit of detection.
    Results
    Under the optimized experimental conditions, the calibration graph was linear in the range of 0.02 − 12.0 µg.mL−1 of verapamil with a detection limit of 0.008 µg.mL–1.
    Conclusion
    The proposed method was found to be suitable and accurate for the determination of verapamil and the validated method was successfully used for analysis of verapamil in EBC of patients receiving verapamil with the satisfactory results.
    Keywords: Verapamil, Fluorescence enhancement, SDS, Biosensing
  • Saeid Yaripour, Ali Mohammadi *, Somayeh Mousavi , Isa Esfanjani , Naghmeh Arabzadeh , Shahla Mozaffari Pages 57-64
    Background
    In the present study, an electromembrane extraction (EME) followed by a simple high performance liquid chromatography with ultraviolet detection (HPLC-UV) was developed and validated for simultaneous determination of 2-nitrophenol (2-NP) and 4-nitrophenol (4-NP) in pharmaceutical industrial wastewater sample. Main parameters of electromembrane extraction were evaluated and optimized.
    Methods
    1-octanol was immobilized in the pores of a polypropylene hollow fiber as supported liquid membrane. As a driving force, a 100 volt electrical voltage was applied to transfer the analytes from the sample solution (pH, 7.5) through the supported liquid membrane into an acceptor solution (pH, 12).
    Results
    The best enrichment factors were obtained 36 and 72 for 2-NP and 4-NP, respectively after 15 minutes of extraction. The effect of carbon nanotube, as a solid nano-sorbent on EME efficiency, was also evaluated. The proposed method provided the linearity in the range of 10-1000 ng/mL for 2-NP (R2> 0.9997) and 4-NP (R2> 0.9999) with repeatability range (% RSD) between 2.6-10.3 % (n = 3). The limit of detection was 3 ng/mL and the limit of quantitation was 10 ng/mL.
    Conclusion
    Finally, the method was applied for the determination of 2-NP and 4-NP in industrial wastewater samples with relative recoveries in the range between 67–76 %. EME improved the sensitivity of HPLC-UV for the determination of trace concentrations of these analytes.
    Keywords: Electromembrane extraction, HPLC-UV, 2-Nitrophenol, 4-Nitrophenol, Wastewater
  • Musadiq Hussain Bhat *, Mufida Fayaz , Amit Kumar , Alamgir Ahmad Dar , Ashok Kumar Jain Pages 65-69
    Background
    The present study was carried out for determination of amino acid content in tubers of Dioscorea bulbifera using reverse-phase high-performance liquid chromatography.
    Methods
    The method involved the vapor phase hydrolysis of the sample, automated derivatisation of the amino acids with the aid of AccQ-Fluor reagent kit, separated on a high performance liquid chromatography equipped with photo diode array (HPLC-PDA) at 254 nm having column temperature of 37 ºC.
    Results
    The proportional molar concentration for each amino acid was calculated based on the concentration of standard amino acids and expressed as μg amino acid/mg sample. Methionine, aspartic acid and leucine were major components while as tyrosine was found minor from the plant on dry weight basis.
    Conclusion
    The method is reliable, simple and economical for determining the amino acid content of Dioscorea bulbifera tubers.
    Keywords: Dioscorea bulbifera, Amino acids, High performance liquid chromatography, AccQ-Fluor
  • Babak Elyasifar, Sevda Jafari, Somayeh Hallaj, Nezhadi, Florence Chapeland, leclerc, Gwenaël Ruprich, Robert, Azita Dilmaghani * Pages 70-77
    Background
    Halophilic bacteria are potent organisms in production of novel bioactive antimicrobial compounds which might be considered in drug innovation and control of plant pathogens. Salt deserts in Semnan province are of the most permanent hypersaline areas in the North of Iran. Despite the importance of these areas, there is no scientific report regarding the biodiversity and potency of their halophilic bacteria. Thus, aforementioned areas were selected to detect the halophilic bacteria.
    Methods
    Here, seven strains were isolated and cultured on their molecular and biochemical properties were characterized. To determine the antibiotic potency of the isolates, agar well diffusion method was conducted. Phylogenetic analysis was done to reveal the isolates relationship with previously known strains.
    Results
    As a result, growth of the strains in the medium containing 5 to 20% (w/v) NaCl determined that the majority of the isolates were moderately halophile. Catalase activity of all strains was positive. The results represented that D6A, Dar and D8B have antimicrobial effects against different plant and human pathogens. Phylogenic tree analysis also showed that two strains of D6A and Dar are belonged to Bacillus subtilis and D8B is belonged to Virgibacillus olivae. The bacteria extracts were evaluated for their antifungal and antibacterial activities on human and Plant pathogenic strains. The MIC of the extract B. subtilis against was found active against human pathogenic fungi and Plant pathogenic bacteria and fungi, ranging from 12.5 to 25 µg/mL.
    Conclusion
    This study highlights the therapeutic and prophylactic potential of B. subtilis extracts as antibacterial and antifungal agents.
    Keywords: Halophilic bacteria, Antimicrobial, Pathogen, Dagh Biarjmand, Haj Aligholi salt deserts
  • Mir Babak Bahadori , Solmaz Asnaashari , Hossein Nazemiyeh * Pages 78-81
    Background
    Ruscus specie are used as traditional medicine, food, and foliage. The aim of this work is the determination of fatty acid composition of Ruscus hyrcanus as a native medicinal plant of Iran for the first time together with comparison of different esterification methods.
    Methods
    Two different esterification methods were used for preparation of esterified fatty acids from different extracts of underground and aerial parts of the herb. GC/MS analysis were used for identification and quantification of fatty acids. Finally, the results were compared.
    Results
    Findings showed that R. hyrcanus is rich in essential fatty acids such as linoleic acid (13-25%) and linolenic acid (23-44%). Also, oil samples contain remarkable amount of palmitic acid (19-57%).
    Conclusion
    The results showed that R. hyrcanus could be considered as a source of essential fatty acids. Also, it could be concluded that a simple esterification method with methanolic KOH and 2 min vortex is suitable for fatty acid analysis of Ruscus species.
    Keywords: Esterification, Fatty acid, Linoleic acid, Linolenic acid, Ruscus