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Research in Pharmaceutical Sciences - Volume:1 Issue: 2, Oct 2006

Research in Pharmaceutical Sciences
Volume:1 Issue: 2, Oct 2006

  • 54 صفحه،
  • تاریخ انتشار: 1384/12/20
  • تعداد عناوین: 8
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  • A. Jafarian, S.E. Sajjadi, A. Mohammadzadeh Page 59
    Garlic and onions as dietary constituents and medicines have been used for many disorders which dates back to the early civilization. It has been shown that different species of Allium have immunomodulating effects. In this study, we sought to determine if methanolic and chloroformic extracts of Allim fistulosum L. (Leek) have any effect on cell-mediated immune response in mice. Methanolic and chloroformic extracts of A. fistulosum bulbs were prepared by maceration. To study the effects of A. fistulosum on acquired immunity, groups of Balb/c mice (n = 8-12) were used. Sheep red blood cell (SRBC) was injected (s.c., 1x108 cells/ml, 0.02 ml) and 5 days later, different extracts (1, 10, 100 and 1000 mg/kg), betamethasone (4 mg/kg) or normal saline were given i.p. After 1 h SRBC was injected to footpad (s.c., 1x108 cells/ml, 0.02 ml) and footpad swelling was measured up to 72 h. To see the effects of A. fistulosum on intrinsic immunity the same procedure was used, but animals only received one injection of SRBC 1 h after i.p. injection of test compounds. Our findings showed that SRBC induced an increase in paw swelling with maximum response at 7 h. Betamethasone inhibited paw thickness in both models. In both intrinsic and acquired immunity models, chloroformic and methanolic extracts of A. fistulosum bulbs significantly reduced paw thickness at the doses of 100 and 1000 mg/kg, but no clear dose-response was observed.
  • H. Sadeghi, Aliabadi, A. Jafarian, S.A. Fatemi, G. Shahidi, S.A. Emami Page 66
    Exploration of natural products with antitumoral effects such as etoposide, tenioposide, camptothecin and paclitaxel from conifers provoked us to do some research on anti-tumoral activity of Iranian medicinal plants. Ten different species of Iranian conifers aerial parts were collected across the country. The relative potency of methanolic extract were investigated on the inhibition of topoisomerase I on yeasts (Sacharomyces cerevisiae, RS 322N and S. cerevisiae, RS 188N, as wild type) using agar diffusion, turbidimetry and agar dilution procedures. Briefly, 0.1 ml of extracts (20 mg/ml) were added to the yeast culture and the obtained zone of inhibition were evaluated compare to the control (camptothecin, 2 μg/ml). Zones of inhibition >12 mm on mutant type and no inhibition effect on wild type were considered as positive results or cytotoxicity. For agar dilution assay, different dilutions of extracts (5, 10, 20, 40, 80 mg/ml) were applied and inhibition of yeast growth was considered as positive result. In turbidimetric assay no turbidity was evaluated as cytotoxicity. Minimum inhibitory concentration was determined by agar dilution and turbidimetric procedures. To determine minimum biocidal concentration, samples were transferred from turbidimetric cells to solid media. According to the agar diffusion results, none of the extracts showed specific cytotoxicity on mutant yeast. The results obtained from growth inhibition of Platycladus orientalis extracts were shown to have some good cytotoxic effects on both mutant and wild type. In conclusion, agar dilution and turbidimetry results were similar according to the high concentration of extracts and this means that the cytotoxic effects of these plants on yeasts are not specific.
  • G.A. Khodarahmi, F. Hassanzadeh, A. Jafarian, A.H. Chiniforoosh, A.M. Hajseyedabutorabi Page 73
    Aromatase inhibitors have been used as a second line therapy after tamoxifen, in estrogen-receptor positive (ER+) women to reduce estrogen concentration in plasma and breast tumors. It has been shown that benzofuran(phenylmethyl)imidazoles are potent aromatase inhibitors at nano-molar concentrations, about 1000 times more potent than aminoglutetimide. In this study, cytotoxic activity of some of these potent aromatase inhibitors (compounds 1-6) on MCF-7 and Hela cell lines were evaluated. MCF-7 and Hela cells were cultured on RPMI medium and the cells obtained after the third generation were used in this study. The cytotoxic activity of the compounds was first screened at 20 and 100 µM. The IC50 values were then determined, using MTT method. Briefly, after 24 h incubation of the cells, the compounds, doxorubicine and the medium were added to the cells and incubated for further 48 h (37 oC, 5% CO2). The MTT solution was then added and the absorbance was measured by ELISA plate reader at 540 nm after 4 h incubation. The results indicated that the IC50 values for compounds 1-6 were around 35-80 µM for MCF-7 and 47-85 µM for Hela cells. Compound 5, the 4-chloro derivative, showed almost the highest toxicity on both cell lines. i.e. IC50s were 35 µM and 55 µM for MCF-7 and Hela cells, respectively. The cytotoxic activity could be in part due to the aromatase inhibition but other mechanisms like DNA degradation may also be involved.
  • M. Ani, A.A. Moshtaghie, M. Aghadavood Page 80
    Lead is a common toxic agent which impairs various organs functions of the body. The basis of this toxicity is believed to be the negative influence on enzymatic system of cells. In the past few years, increasing consideration has been given to interactions occurring between lead and some essential metals including Se and Zn. Based on the finding that some trace elements could reverse the toxicity of lead on tissue functions this work was performed to study the protective effects of Zn and Se against lead toxicity. Thus changes in acetyl cholinesterase (AchE) activity in brain regions were investigated in different conditions. Four groups of rats were chosen. In acute study, i.p. administration of Pb (13.5 mg/kg) for 2 weeks reduced the activity of AchE in the cortex by 28.7% but Pb in presence of Zn (0.5 mg/kg) and Se (0.4 mg/kg) inhibited AchE activity only by 11.5% and 25%, respectively, such inhibition in mid-brain were 44.7%, 18.2%, 32% and in the cerebellum 48.2%, 38.4% and 12.0%. In chronic study, animals were administered Pb alone (4 mg/kg) or in the presence of Se or Zn for 60 days. Following these treatments, AchE activities in the cortex were reduced by 41.5%, 22.0% and 39.6%, respectively. These inhibitions in mid-brain were 56.0%, 37.6%, 54.5% and in cerebellum 46.0%, 45.0%, 32.6%. It is concluded that lead had toxic effect on AchE activity in different brain regions and Zn and Se could reverse this inhibition to some extent.
  • M. Mobini, Dehkordi, I. Nahvi, K. Ghaedi, M. Tavassoli Page 85
    Several strains of Saccharomyces cerevisiae were isolated from different sources. These strains were under taken for ethanol tolerance analysis and growth under stress condition. Exponential phase to various concentrations of ethanol (2–26% v/v) for 1 h was used for isolation of resistant strains. Viable cells were isolated and purified by inoculation of diluted samples on yeast extract peptone agar medium at 30 ºC for 24 h. All resistant strains were grown on solid aerobic low peptone medium supplemented with 24% (v/v) ethanol but had variations at growth intensity in this condition. Invertase enzyme activity in yeast isolates was measured and comparing with control samples resistant strains did not show significant difference in the enzyme activity. As resistant strains to ethanol have different content of fatty acids in cell membrane and resistance mechanisms, they can be used in various fields of biotechnology such as ethanol production, recombinant-protein expression, trehalose production and novel drug development.
  • V. Hajhashemi, A. Ghannadi, S. Sedighifar Page 92
    Extracts obtained from the aerial parts of Stachys lavandulifolia (Lamiaceae) are used in Iranian folk medicine as remedies for the treatment of various painful and inflammatory diseases. For evaluation of its probable analgesic and anti-inflammatory effects, hydroalcoholic, polyphenolic and boiled extracts of the aerial parts of the herb were prepared and their analgesic effects were studied in mice using formalin, acetic acid-induced writhing and light tail flick tests. Carrageenan test in rats was used for assessment of anti-inflammatory activity of the extracts. Results showed that all the tested extracts were able to reduce the abdominal constrictions in acetic acid-induced writhing test. These extracts also significantly (P<0.001) suppressed both phases of formalin test. In light tail flick test, none of the extracts showed analgesic activity. Only polyphenolic extract at a dose of 2 g/kg when given p.o. or i.p. significantly (P<0.05) inhibited carrageenan-induced paw oedema. Results of the present study confirm the traditional use of Stachys lavandulifolia for the treatment of painful and inflammatory conditions and calls for further investigations to determine the active chemical constituent(s).
  • A. Gholamhoseinian Najar, M. Mosavi Nejad, S. Mansouri Page 99
    Urinary tract infections (UTIs) are significant health problem, with Escherichia coli as the primary pathogen in proximally 80% of cases. The adhesion of E coli to the host cell can be influenced by cell surface hydrophobicity (CSH) and is an important factor for the development of infections. This study was conducted to find the relation between CSH and one of the adhesions (mannose resistant haemagglutin, MRHA) and a virulence factor (haemolysin), in the bacterial isolates from UTIs and comparison of the UTI isolates with normal faecal flora. The results showed a significant difference in the expression of MRHA in the UTIs compared to that of faecal flora (48% and 12%, respectively, P = 0.012). CSH was determined by two methods of salt aggregation test and bacterial adhesion to hydrocarbons. The results of these tests were correlative and UTIs isolates were found to be more hydrophobic than the normal faecal flora, while the standard strains of enterohaemorrhagic E coli were more hydrophobic than the normal faecal flora. Hemolysin production was higher in the isolates from UTI (28% in UTIs compared to 6% in faecal flora P = 0.0035). In conclusion, we found that the pathogenic E. coli express more MRHA, are more hemolytic and have a higher cell surface hydrophobicity which may help them to start an infection.
  • B. Naghibi, T. Ghafghazi, V. Hajhashemi, A. Talebi, D. Taheri Page 104
    The aim of this study was to investigate the protective role of vitamin E against vancomycin-induced nephrotoxicity. There are some evidences that oxidative injury could be involved in its pathogenesis. Vitamin E at doses of 50, 100 and 200 mg/kg were administered s.c. to rats 30 min prior to i.p. injection of 200 mg/kg vancomycin (VAN). Drug administrations were done every 12 h for 7 days. Afterwards, urine and blood samples were collected and several parameters including activity of urinary γ-glutamyl-transferase (GGT), alanine aminopeptidase and lactate dehydrogenase (LDH), serum urea and creatinine (Cr) concentrations and changes in body and kidney weights were measured. In the animals which received only VAN, the activity of urinary GGT decreased and the activity of LDH in urine increased significantly compared to controls. Serum urea and Cr concentrations and the weight of animals’ kidneys increased and body weights decreased significantly in this group compared to controls. Vitamin E at the dose of 200 mg/kg, normalized the GGT and LDH activity. In addition, this dose ameliorated the rise in serum urea and Cr concentrations and improved the changes in kidney and body weights significantly. Other two doses of vitamin E only could modify the changes in body weights. There were marked pathologic changes in tubules of kidneys of VAN treated animals. The tissue injury was prevented only by 200 mg/kg vitamin E, however it remained different from controls. Vitamin E itself did not show any adverse effects on kidneys. It seems that VAN-induced nephrotoxicity might be at least partly due to free radical formation and vitamin E can attenuate its toxicity.