فهرست مطالب

Research in Pharmaceutical Sciences
Volume:8 Issue: 2, May 2013

  • تاریخ انتشار: 1391/09/11
  • تعداد عناوین: 8
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  • M. Nematbakhsh, V. Hajhashemi, A. Ghannadi, A. Talebi, M. Nikahd Pages 71-77
    Cisplatin (CP) as an important anti-tumor drug causes nephrotoxicity mainly by oxidative stress and renin-angiotensin system (RAS). Since flavonoids have high antioxidant activity and probable role in the inhibition of RAS, this study was designed to investigate the protective effect of hydroalcoholic extract and flavonoid fraction of Morus alba leaves on cisplatin-induced nephrotoxicity in rat. Extracts of Morus alba leaves were prepared and analyzed Phytochemically. Male rats (160-200 g) were used in this study (n=7-9). Normal group received 0.2 ml normal saline intraperitoneally (i.p.) once daily for ten days. Control animals received CP on the third day and saline in the remaining days. Other groups received either hydroalcoholic extract (200, 400 and 600 mg/kg, i.p.) or flavonoid fraction (50, 100 and 200 mg/kg, i.p.) for two days before CP administration and thereafter until tenth day. Serum concentrations of blood urea nitrogen (BUN), creatinine (Cr) and nitric oxide were measured using standard methods. Also left kidneys were prepared for pathological study. The serum levels of BUN and Cr increased in animals received CP. Hydroalcoholic extract was ineffective in reversing these alterations but flavonoid fraction (50 and 100 mg/kg) significantly inhibited CP-induced increases of BUN and Cr. None of the treatments could affect serum concentration of nitric oxide. Flavonoid fraction could also prevent CP-induced pathological damage of the kidney. It seems that concurrent use of flavonoid fraction of Morus alba with CP can protect kidneys from CP-induced nephrotoxicity.
    Keywords: A Honarmand, M Safavi, P Kashefi, B Hosseini, S Badiei
  • M. Nikbakht Dastjerdi, Mr Salahshoor, M. Mardani, M. Rabbani, B. Hashemibeni, M. Gharagozloo, M. Kazemi, N. Esmaeil, Sh Roshankhah, R. Golmohammadi, M. Mobarakian Pages 79-89
    Sirtuin1 (SIRT1) is an enzyme that deacetylates histones and several nonhistone proteins including p53 during stress and plays an important role in the survival of tumor cells. Hereby, this study describes the potency of salermide as a SIRT1 inhibitor to induce apoptosis in the MCF-7 and MRC-5 cell lines. MCF7 and MRC-5 cell lines were cultured in RPMI-1640 and treated with or without salermide at concentration of 80.56 μmol/L, based on the half-maximal inhibitory concentration (IC50) index at different times (24, 48 and72 h). The IC50 value was established for the salermide in MCF-7. The percentage of apoptotic cells was measured by flow cytometry. Real-time quantitative RT-PCR was performed to estimate the mRNA expression of sirtuin1 in MCF-7 and MRC-5 with salermide at different times. ELISA and Bradford protein techniques were used to detect endogenous levels of total and acetylated p53 protein generated in MCF-7 and MRC-5 cells. Our findings indicated that salermide can induce apoptosis in MCF-7 significantly more effective than MRC-5 cells. We showed that the expression of SIRT1 was dramatically down-regulated by increasing the time of salermide treatment in MCF-7 but not MRC-5 and that the acetylated and total p53 protein levels were increased more in MCF-7 than MRC-5. Salermide, by decreasing the expression of sirtuin1 gene, can induce acetylation of P53 protein and consequently induce significant cell death in MCF-7 that was well tolerated in MRC-5.
  • F. Hadizadeh, B. Rahimi, E. Taghiabadi, M. Razavi, G. Karimi Pages 91-95
    In this study the anticonvulsant effect of two dihydropyridine derivatives [diethyl -1,4- dihydro -2,6- dimethyl -4-(4- fluoro benzyl-2- methylthio -5- imidazolyl)-3,5- pyridine dicarboxilat (A) and diethyl -1,4- dihydro -2,6- diethyl -4-(4- fluoro benzyl-2- methylthio -5- imidazolyl)-3,5- pyridine dicarboxilat (B)] by pentylenetetrazole (PTZ) and electroshock in mice was evaluated. The latency and HLTE (hind limb tonic extensions), the duration of HLTE and the mortality protection in pentylenetetrazole test and the HLTE duration in electroshock test were assessed. Both compounds had significant differences with negative control in all doses used. There was no significant difference between nifedipine and B (96.7 and 169.2 mg/kg doses) in the starting point of HLTE and between nifedipine and A (62.2 and 108.9 mg/kg doses) in the duration of HLTE in the PTZ test. Also, there was no significant difference between nifedipine and B (96.7 and 169.2 mg/kg doses) and A (62.2 and 108.9 mg/kg doses) in electroshock test. All doses of A and B and nifedipine showed less effect than phenytoin and valproate. This study showed that both A and B have anticonvulsant activity in the PTZ-induced seizure model and the MES test. These compounds, thus, might be useful in the petit mal and grand mal epilepsy.
  • L. Saghaie, M. Shahlaei, A. Fassihi Pages 97-112
    Quantitative relationships between structures of twenty six of 2-mercaptoimidazoles as C-C chemokine receptor type 2 (CCR2) inhibitors were assessed. Modeling of the biological activities of compounds of interest as a function of molecular structures was established by means of genetic algorithm multivariate linear regression (GA-MLR) and genetic algorithm (GA-ANN). The results showed that, the pIC50 values calculated by GA-ANN are in good agreement with the experimental data, and the performance of the artificial neural networks regression model is superior to the multivariate linear regression-based (MLR) model. With respect to the obtained results, it can be deduced that there is a non-linear relationship between the pIC50s and the calculated structural descriptors of the 2-mercaptoimidazoles. The obtained models were able to describe about 78% and 93% of the variance in the experimental activity of molecules in training set, respectively. The study provided a novel and effective approach for predicting biological activities of 2-mercaptoimidazole derivatives as CCR2 inhibitors and disclosed that combined genetic algorithm and GA-ANN can be used as a powerful chemometric tools for quantitative structure activity relationship (QSAR) studies.
  • A. Ghannadi, A. Plubrukarn, K. Zandi, K. Sartavi, A. Yegdaneh Pages 113-118
    Alcoholic extracts of 8 different types of seaweeds from Iran's Persian Gulf were tested for their antimalarial and acetylcholinesterase enzyme (AChE) inhibitory activities for the first time. A modified Ellman and Ingkaninan method was used for measuring AChE inhibitory activity in which galanthamine was used as the reference. The antimalarial assay was performed using microculture radioisotope technique. Mefloquine and dihydroartemisinin were uased as the standards. The extract of Sargassum boveanum (Sargasseae family) showed the highest AChE inhibitory activity (IC50 equals to 1 mg ml-1) while Cystoseira indica (Cystoseiraceae family) exhibited the least activity (IC50 of 11 mg ml-1). The species from Rhodophyta (Gracilaria corticata and Gracilaria salicornia) also showed moderate activities (IC50 9.5, 8.7 mg ml-1, respectively). All extracts were inactive in antimalarial assay.
  • M. Khazaei, E. Salehi Pages 119-123
    Cardiovascular disease is the common cause of mortality in diabetic subjects. Recently, it is indicated that peroxisome proliferator-activated receptors (PPARs) agonists have beneficial effect on cardiovascular system especially on angiogenesis. PPARs have three isotypes: PPARα, PPARβ/δ and PPARγ. In this study, we evaluated the effect of bezafibrate as pan PPAR agonist on myocardial capillary density in type I diabetic rats. Eighteen male wistar rats were randomly divided into three groups (n=6 each): control, diabetic and diabetic+bezafibrate (400 mg/kg/day) by gavage every day. Diabetes was induced by a single dose of streptozotocin (55 mg/kg), intraperitoneally. After 21 days, capillary density in the myocardial tissue was evaluated by immunohistochemical staining and reported as capillaries per mm2. Blood samples were taken before and after the experiment. Diabetes was associated by lower serum nitric oxide (NO) concentration and reduced myocardial capillary density compared to control group (121.71 ± 13.32 vs. 158.78 ± 11.08 /mm2; P<0.05). Administration of bezafibrate significantly increased serum NO level and improved angiogenesis in myocardial tissue of diabetic animals (170.24 ± 15.76 vs.121.71 ± 13.32 /mm2; P<0.05). There was a positive correlation between serum NO concentration and myocardial capillary density (r=0.90). Activation of all isotypes of PPAR by bezafibrate improves heart capillary density in diabetic animals and it seems that it can be considered for treatment or prevention of coronary heart disease in diabetic subjects.
  • V. Kamalakkannan, A. Puratchikody, L. Ramanathan Pages 125-136
    Candesartan cilexetil (CC) is a newer class of angiotensin II receptor antagonist used for the treatment of hypertension. The solubility of the CC is very poor and its oral bioavailability is only 15%. The controlled-release polar lipid microparticles of CC (formulations F1, F2, F3 and F4) were prepared using variable erodible lipophilic excipients like hydrogenated castor oil, stearic acid, cetostearyl alcohol and carnauba wax by fusion method. The particle sizes of polar lipid microparticles were less than 50 microns and they were irregular in shape. Drug content ranged between 98.96 ± 2.1 and 101.9 ± 1.6% were present in all the formulations. The formulation F3 showed better drug release throughout the study period in a controlled release manner. Moreover, the in vitro release showed that all the formulations were best fitted to Higuchi model. Accelerated stability studies indicated that there was no significant changes in the chemical and physical characteristics of the formulated drug product during initial and at the end of the study period. The FTIR and DSC studies showed that there was no interaction between the drug and lipophilic excipients and no polymorphic transitions in all formulations. The X-ray diffraction peak of solid dispersion indicated that the crystalline nature of CC disappeared and no new peaks could be observed, suggesting the absence of interaction between drug and excipients.
  • H. Sadraei, Y. Shokoohinia, Se Sajjadi, M. Mozafari Pages 137-144
    Prangos ferulacea is a plant found in the Mediterranean and Middle-east regions used as carminative, anti-flatulent, emollient and antibacterial herb. It is believed that the coumarins are responsible for some of known effects of Prangos. In this research the relaxant effects of P. ferulacea coumrin rich extract as well as osthole as its main prenylated coumarins were investigated on rat ileum contraction in vitro. Relaxant effect of osthole and P. ferulacea extract were examined on contraction induced by KCl, acetylcholine (ACh) and electrical field stimulation (EFS) and compared with propantheline and nifedipine. The acetone extract of P. ferulacea concentration-dependently relaxed ileum contraction induced by KCl (IC50=1.3 ± 0.25 mg/ml), ACh (IC50=7.7 ± 1.1 mg/ml) and EFS (IC50=8.8 ± 1.4 mg/ml), while, the extract at lower concentration (4 mg/ml) potentiated the ACh and EFS responses. Unlike the extract, osthole did not potentiate the ileum contraction but concentration-dependently inhibited ileum contractile responses to KCl (IC50=2.2 ± 0.7 mg/ml), ACh (IC50=2.5 ± 0.7 mg/ml) and EFS (IC50=2.8 ± 0.24 mg/ml). Propantheline concentration dependently inhibited the ileum response to ACh, with IC50 value of 0.61 ± 0.09nM without affecting the KCl response. As expected, the EFS response was only partially reduced. Nifedipine (0.2-50 nM) inhibited tonic contraction induced by KCl with IC50 value of 2.5 ± 0.8 nM but only partially inhibited the response to ACh. However, the response to EFS was reduced only by 33%. These results confirmed both potentiatory and inhibitory action of P. ferulacea extract on rat ileum contractile activity. Osthole is responsible for the inhibitory effect but potentiating components are not yet known.