Publications by authors named "Yaser Azizi"

20 Publications

  • Page 1 of 1

Human amniotic membrane mesenchymal stem cell-conditioned medium reduces inflammatory factors and fibrosis in ovalbumin-induced asthma in mice.

Exp Physiol 2021 Feb 7;106(2):544-554. Epub 2021 Jan 7.

Physiology Research Centre, Iran University of Medical Sciences, Tehran, Iran.

New Findings: What is the central question of this study? Is mesenchymal stem cell-conditioned medium capable of improving the pathological alterations of ovalbumin-induced asthma in mice? What is the main finding and its importance? Our study indicated that human amniotic membrane mesenchymal stem cell-conditioned medium is capable of modulating inflammation, fibrosis, oxidative stress and the pathological consequences of ovalbumin-induced allergic asthma in mice.

Abstract: Paracrine factors secreted by mesenchymal stem cells (MSCs) have immunomodulatory, anti-inflammatory and antifibrotic properties, and the conditioned medium (CM) of these cells might have functional capabilities. We examined the effects of human amniotic membrane MSC-CM (hAM-MSC-CM) on ovalbumin (OVA)-induced asthma. Forty male Balb/c mice were randomly divided into the following four groups: control; OVA (sensitized and challenged with OVA); OVA+CM (sensitized and challenged with OVA and treated with hAM-MSC-CM); and OVA+Placebo (sensitized and challenged with OVA and treated with placebo). Forty-eight hours after the last challenge, serum and bronchoalveolar lavage fluid samples were collected and used for evaluation of inflammatory factors and cells, respectively. Lung tissue sections were stained with Haematoxylin and Eosin or Masson's Trichrome to evaluate pathological changes, and oxidative stress was assessed in fresh lung tissues. Treatment with hAM-MSC-CM significantly hindered histopathological changes and fibrosis and reduced the total cell count and the percentage of eosinophils and neutrophils in bronchoalveolar lavage fluid. Furthermore, it reduced serum levels of immunoglobulin E, interleukin-4, transforming growth factor-β and lung malondialdehyde. It also increased serum levels of interferon-γ and interleukin-10, in addition to the enzymatic activity of glutathione peroxidase, catalase and superoxide dismutase in lung tissue in comparison to the OVA and OVA+Placebo groups. This study showed that administration of hAM-MSC-CM can improve pathological conditions, such as inflammation, fibrosis and oxidative stress, in OVA-induced allergic asthma.
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http://dx.doi.org/10.1113/EP088911DOI Listing
February 2021

Human amniotic membrane mesenchymal stem cells-conditioned medium attenuates myocardial ischemia-reperfusion injury in rats by targeting oxidative stress.

Iran J Basic Med Sci 2020 Nov;23(11):1453-1461

Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Objectives: Ischemic heart diseases (IHD) are one of the major causes of death worldwide. Studies have shown that mesenchymal stem cells can secrete and release conditioned medium (CM) which has biological activities and can repair tissue injury. This study aimed to investigate the effects of human amniotic membrane mesenchymal stem cells (hAMCs)-CM on myocardial ischemia/reperfusion (I/R) injury in rats by targeting oxidative stress.

Materials And Methods: Male Wistar rats (40 rats, weighing 200-250 g) were randomly divided into four groups: Sham, myocardial infarction (MI), MI + culture media, and MI + conditioned medium. MI was induced by ligation of the left anterior descending coronary artery for 30 min. After 15 min of reperfusion, intramyocardial injections of hAMCs-CM or culture media (150 μl) were performed. At the end of the experiment, serum levels of cardiac troponin-I (cTn-I), myocardial levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as cardiac histological changes were evaluated.

Results: HAMCs-CM significantly decreased cTn-I and MDA levels and increased SOD and GPx activities (<0.05). In addition, hAMCs-CM improved cardiac histological changes and decreased myocardial injury percentage (<0.05).

Conclusion: This study showed that hAMCs-CM has cardioprotective effects in the I/R injury condition. Reduction of oxidative stress by hAMCs-CM plays a significant role in this context. Based on the results of this study, it can be concluded that hAMCs-CM can be offered as a therapeutic candidate for I/R injury in the future, but more research is needed.
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http://dx.doi.org/10.22038/ijbms.2020.47572.10952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671430PMC
November 2020

Conductive carbon nanofibers incorporated into collagen bio-scaffold assists myocardial injury repair.

Int J Biol Macromol 2020 Nov 2;163:1136-1146. Epub 2020 Jul 2.

Physiology Research Centre, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Currently, treatment of myocardial infarction considered as unmet clinical need. Nanomaterials have been used in the regeneration of tissues such as bone, dental and neural tissue in the body and have increased hope for revitalizing of damaged tissues. Conductive carbon base nanomaterials with its superior physicochemical properties have emerged as promising materials for cardiovascular application. In this study, we applied a biosynthetic collagen scaffold containing carbon nanofiber for regenerating of damaged heart tissue. The collagen-carbon nanofiber scaffold was fabricated and fully characterised. The scaffold was grafted on the affected area of myocardial ischemia, immediately after ligation of the left anterior descending artery in the wistar rat's model. After 4 weeks, histological analyses were performed for investigation of formation of immature cardio-myocytes, epicardial cells, and angiogenesis. Compared to untreated hearts, this scaffold significantly protects heart tissue against injury. This improvement is accompanied by a reduction in fibrosis and the increased formation of a blood vessel network and immature cardio-myocytes in the infarction heart. No toxicity detected with apoptotic and TUNEL assays. In conclusion, the mechanical support of the collagen scaffold with carbon nanofiber enhanced the regeneration of myocardial tissue.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.06.259DOI Listing
November 2020

Apigenin attenuates doxorubicin induced cardiotoxicity via reducing oxidative stress and apoptosis in male rats.

Life Sci 2019 Sep 4;232:116623. Epub 2019 Jul 4.

Physiology Research Center and Department of Physiology, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Aims: Doxorubicin, an antibiotic belonging to anthracycline family, has been used for treatment of malignancies. Cardiotoxicity is the main adverse effect of doxorubicin. Apigenin, as a flavonoid, has antioxidant, anti-inflammatory and anti-tumoral properties. The aim of this study was the assessment of any protective effect of apigenin on cardiotoxicity induced by doxorubicin.

Main Methods: 40 male Wistar rats were randomly divided into 4 groups: control, cardiotoxicity (DOX), apigenin treated group (DOX + Api 25) and apigenin group (Api 25). At the end of the experiment, the markers of cardiac function (%EF, %FS, LVIDs, LVIDd), cardiac and liver injury (LDH, CK-MB, cTn-I, ALT, and AST), cardiac apoptosis (Bax, Bcl-2 and Caspase3), cardiac oxidative stress (SOD, GSH, MDA) and cardiac fibrosis were measured.

Key Findings: Apigenin improved cardiac functional parameters. The levels of cardiac and liver injury markers were significantly decreased in DOX + Api 25 compared to DOX. Treatment with apigenin caused significant decrease in percentage of cardiac fibrosis in comparison with DOX. Apigenin in DOX + Api 25 group led to significant decrease in apoptotic proteins (Casp3, Bax) and a significant increase in anti-apoptotic proteins (Bcl2). In apigenin treatment groups, SOD levels significantly increased while a significant decrease was observed in MDA. The amount of GSH in DOX + Api 25 had no significant change in comparison to control and Api 25 groups.

Significance: Apigenin reduced cardiac injuries induced by DOX through anti-fibrotic, antioxidant and anti-apoptotic properties. It seems that apigenin prevents cardiac injuries and improves cardiac function.
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http://dx.doi.org/10.1016/j.lfs.2019.116623DOI Listing
September 2019

Sumatriptan protects against myocardial ischaemia-reperfusion injury by inhibition of inflammation in rat model.

Inflammopharmacology 2019 Oct 30;27(5):1071-1080. Epub 2019 Mar 30.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.

Ischemic heart disease is a leading cause of death on a global scale, placing major socio-economic burdens on health systems worldwide. Myocardial ischaemia and reperfusion (I/R)-induced tissue injury is associated with alteration in activity of inflammatory system and nitric oxide pathway. Sumatriptan, which is mainly used to relieve migraine headache, has recently been shown to exert anti-inflammatory properties. In this study, we aimed to assess the possible cardioprotective effect of sumatriptan in a rat model of I/R injury. Male Wistar rats were subjected to 30-min ligation of left anterior descending coronary artery and 120-min reperfusion. Animals were randomly divided into five groups: (1) Sham (2) I/R (3) I/R treated with sumatriptan (0.3 mg/kg i.p.) 20 min after induction of I/R rats, (4) GR127935 (a selective antagonist of 5-HT1B/D serotonin receptors; 0.3 mg/kg) 20 min after induction of I/R, and (5) GR127935 (0.3 mg/kg) 15 min before administration of sumatriptan. Post-infarct treatment with sumatriptan increased left ventricular function, which was damaged in I/R animal's heart. Sumatriptan (0.3 mg/kg) decreased lipid peroxidation, CK-MB and lactate dehydrogenase levels; tumor necrosis factor concentration; and Nf-ҡB' protein production. Treatment with sumatriptan significantly increased the endothelial nitric oxide synthase (eNOS) expression consequences nitric oxide metabolites' level in I/R rats. Also, injection of sumatriptan remarkably decreased myocardial tissue injury assessed by histopathological study. These findings suggest that sumatriptan may attenuate I/R injury via modulating the inflammatory responses and endothelial NOS activity. But therapeutic index of sumatriptan is narrow according to the result of this study.
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http://dx.doi.org/10.1007/s10787-019-00586-5DOI Listing
October 2019

Cardioprotective effects of omega-3 fatty acids and ascorbic acid improve regenerative capacity of embryonic stem cell-derived cardiac lineage cells.

Biofactors 2019 May 25;45(3):427-438. Epub 2019 Mar 25.

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

One of the major issues in cell therapy of myocardial infarction (MI) is early death of engrafted cells in a harsh oxidative stress environment, which limits the potential therapeutic utility of this strategy in the clinical setting. Increasing evidence implicates beneficial effects of omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and ascorbic acid (AA) in cardiovascular diseases, in particular their role in ameliorating fibrosis. In the current study, we aim to assess the cytoprotective role of EPA + DHA and AA in protecting embryonic stem cell (ESC)-derived cardiac lineage cells and amelioration of fibrosis. Herein, we have shown that preincubation of the cells with EPA + DHA + AA prior to H O treatment attenuated generation of reactive oxygen species (ROS) and enhanced cell viability. Gene expression analysis revealed that preincubation with EPA + DHA + AA followed by H O treatment, upregulated heme oxygenase-1 (HO-1) along with cardiac markers (GATA4, myosin heavy chain, α isoform [MYH6]), connexin 43 [CX43]) and attenuated oxidative stress-induced upregulation of fibroblast markers (vimentin and collagen type 1 [Col1]). Alterations in gene expression patterns were followed by marked elevation of cardiac troponin (TNNT2) positive cells and reduced numbers of vimentin positive cells. An injection of EPA + DHA + AA-pretreated ESC-derived cardiac lineage cells into the ischemic myocardium of a rat model of MI significantly reduced fibrosis compared to the vehicle group. This study provided evidence that EPA + DHA + AA may be an appropriate preincubation regimen for regenerative purposes. © 2019 BioFactors, 45(3):427-438, 2019.
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http://dx.doi.org/10.1002/biof.1501DOI Listing
May 2019

Axonal degeneration and demyelination following traumatic spinal cord injury: A systematic review and meta-analysis.

J Chem Neuroanat 2019 04 3;97:9-22. Epub 2019 Feb 3.

Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Neurosurgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Brain and Spinal Injuries Research Center (BASIR), Neuroscience Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

The pathophysiology of spinal cord injury (SCI) related processes of axonal degeneration and demyelination are poorly understood. The present systematic review and meta-analysis were performed such to establish quantitative results of animal studies regarding the role of injury severity, SCI models and level of injury on the pathophysiology of axon and myelin sheath degeneration. 39 related articles were included in the analysis. The compiled data showed that the total number of axons, number of myelinated axons, myelin sheath thickness, axonal conduction velocity, and internode length steadily decreased as time elapsed from the injury (P<0.0001). The rate of axonal retrograde degeneration was affected by SCI model and severity of the injury. Axonal degeneration was higher in injuries of the thoracic region. The SCI model and the site of the injury also affected axonal retrograde degeneration. The number of myelinated axons in the caudal region of the injury was significantly higher than the lesion site and the rostral region. The findings of the present meta-analysis show that the pathophysiology of axons and myelin sheath differ in various phases of SCI and are affected by multiple factors related to the injury.
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http://dx.doi.org/10.1016/j.jchemneu.2019.01.009DOI Listing
April 2019

Heparin Enhances the Effects of Mesenchymal Stem Cell Transplantation in a Rabbit Model of Acute Myocardial Infarction.

Niger J Physiol Sci 2018 06 30;33(1):9-15. Epub 2018 Jun 30.

Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

Stem cell transplantation in combination with administration of bioactive compounds has shown promising resultsin treating myocardial infraction (MI). In the current study, we investigated the effect of combining mesenchymal stem cells(MSCs) transplantation with heparin into the infarcted heart rabbits. For this purpose, 35 male New Zealand white rabbitswere randomly divided into five groups: sham, MI, MI+ MSCs, MI+ heparin and MI+MSCs+ heparin. MI was induced by30 min ligation of the left anterior descending coronary artery. The animals of MSCs and MSCs +heparin groups wereinjected cell culture containing MSCs intramyocardially into the infarct area. Functional parameters of the left ventricle byechocardiography, serum levels of VEGF by enzyme-linked immunosorbent assay, size of fibrotic area by Masson'strichrome staining, evaluation of morphology by Haematoxylin-Eosin and capillary density alkaline phosphatase stainingwere compared between groups. Ejection fraction, fractional shortening and levels of VEGF significantly improved in MSCsand MSCs + heparin group (P<0.05). The fibrotic area was significantly reduced (p=0.009) in MSC + heparin treated animalsin comparison with MSCs. Number of live cells and angiogenesis were increased significantly in MSCs + heparin groups incomparison with MSCs (p< 0.05). Although injection of MSCs significantly restored normal function of fibrotic area, wefound that administration of heparin combined with MSCs to infarcted heart of animals could have better effects on LVfunctional parameters in fibrosis area and resulted in superior therapeutic outcome in enhancing neovascularization andimproving cardiac fibrosis.
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June 2018

Natural lavender oil (Lavandula angustifolia) exerts cardioprotective effects against myocardial infarction by targeting inflammation and oxidative stress.

Inflammopharmacology 2019 Aug 2;27(4):799-807. Epub 2018 Aug 2.

Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: The study was conducted to examine therapeutic effects of lavender oil (LO) against myocardial infarction (MI) and its potential mechanisms.

Methods: A rat model of MI was established and LO (100, 200 and 300 mg/kg) was intraperitoneally administrated immediately after ischemia. Anti-inflammatory and antioxidant activity of LO were evaluated by immunohistochemical assay and measurement of SOD, GSH, and MDA. The myocardial injury markers, apoptotic activity and infarct volume were examined by ELISA, TUNEL and TTC staining, respectively.

Results: Compared with the control I/R-Vehicle, the expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) significantly reduced 8 h after reperfusion and expression of interleukin-10 (IL-10) elevated 48 h after reperfusion in LO-treated rats (P < 0.05). Likewise, significant decreases in apoptotic activity, infarct volume and significant restoration of antioxidant endogenous defenses were observed in LO-treated rats (P < 0.05).

Conclusion: Collectively, these findings confirm that LO can be a good candidate to reduce injury after MI.
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http://dx.doi.org/10.1007/s10787-018-0520-yDOI Listing
August 2019

Post-infarct treatment with [Pyr1]apelin-13 exerts anti-remodelling and anti-apoptotic effects in rats' hearts.

Kardiol Pol 2017 9;75(6):605-613. Epub 2017 Feb 9.

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran, Iran, Islamic Republic Of.

Background: Ischaemic heart disease is the main cause of mortality in the world. After myocardial infarction (MI) cardiomyocytes apoptosis and ventricular remodelling have occurred. Apelin is a peptide that has been shown to exert cardioprotective effects.

Aim: The aim of this study was to investigate the anti-apoptotic and anti-remodelling effects of [Pyr¹]apelin-13 in the rat model of post-MI.

Methods: Thirty-six male Wistar rats were randomly divided into three groups: (1) sham, (2) MI, and (3) MI treated with [Pyr¹] apelin-13 (MI+Apel). MI animals were subjected to 30-min ligation of the left anterior descending coronary artery (LAD) and 14 days of reperfusion. Twenty-four hours after LAD ligation, [Pyr¹]apelin-13 (10 nmol/kg/day, i.p.) was administered for five consecutive days. Hypertrophic parameters, left ventricular (LV) remodelling, and gene expression of Apel, apelin receptor (Apelr), Bax, caspase-3 (Casp-3), and Bcl-2 by real-time polymerase chain reaction and cardiomyocytes apoptosis by TUNEL immunostaining were assessed on day 14 post-MI.

Results: Post-infarct treatment with [Pyr¹]apelin-13 improved myocardial hypertrophic and LV remodelling parameters and led to a significant increase in the expression of Apel, Apelr, and Bcl-2, and a decrease in the expression of Bax and Casp-3. Furthermore, treatment with [Pyr¹]apelin-13 decreased cardiomyocyte apoptosis.

Conclusions: [Pyr¹]apelin-13 has anti-hypertrophic, anti-remodelling, and anti-apoptotic effects via overexpression of Apel, Apelr, and Bcl-2 and reduces gene expression of Bax and Casp-3 in the infarcted myocardium, which can in turn lead to repair myocardium.
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http://dx.doi.org/10.5603/KP.a2017.0022DOI Listing
July 2017

Synergistic effects of nitric oxide and exercise on revascularisation in the infarcted ventricle in a murine model of myocardial infarction.

EXCLI J 2015 14;14:1104-15. Epub 2015 Oct 14.

Department of Physiology, Physiology research center, School of Medicine, Iran Universty of Medical Sciences, Tehran, Iran.

It has been shown that density of microvessels decreases in the left ventricular after myocardial infarction (MI). The change of angiogenic and angiostatic factors as the main factors in revascularisation after exercise training in area at risk is not determined yet in MI. Therefore, the aim of the present study was the effect of exercise training and L-arginine supplementation on area at risk angiogenesis in myocardial infarction rat. Four weeks after surgery (Left Anterior Descending Coronary artery Ligation), myocardial infarction rats were divided into 4 groups: Sedentary rats (Sed-MI); L-arginine supplementation (La-MI); Exercise training (Ex-MI) and Exercise + L-arginine (Ex+La). Exercise training (ET) lasted for 10 weeks at 17 m/min for 10-50 min day(-1). Rats in the L-arginine-treated groups drank water containing 4 % L-arginine. After ET and L-arginine supplementation, ventricular function was evaluated and angiogenic and angiostatic indices were measured at ~1 mm from the edge of scar tissue (area at risk). Statistical analysis revealed that gene expression of VEGF as an angiogenic factor, angiostatin as an angiostatic factor and caspase-3 at area at risk decrease significantly in response to exercise training compared to the sedentary group. The capillary and arteriolar density in the Ex groups were significantly higher than those of the Sed groups. Compared to the Ex-MI group, the Ex+La group showed a markedly increase in capillary to fiber ratio. No significant differences were found in infarct size among the four groups, but cardiac function increased in response to exercise. Exercise training increases revascularization at area at risk by reduction of angiostatin. L-arginine supplementation causes additional effects on exercise-induced angiogenesis by preventing more reduction of VEGF gene expression in response to exercise. These improvements, in turn, increase left ventricular systolic function and decrease mortality in myocardial infarction rats.
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http://dx.doi.org/10.17179/excli2015-510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746998PMC
February 2016

Stimulation of Oxytocin Receptor during Early Reperfusion Period Protects the Heart against Ischemia/Reperfusion Injury: the Role of Mitochondrial ATP-Sensitive Potassium Channel, Nitric Oxide, and Prostaglandins.

Acta Med Iran 2015 Aug;53(8):491-500

1Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Postconditioning is a simple and safe strategy for cardioprotection and infarct size limitation. Our previous study showed that oxytocin (OT) exerts postconditioning effect on ischemic/reperfused isolated rat heart. The aim of this study was to investigate the involvement of OT receptor, mitochondrial ATP-sensitive potassium channel (mKATP), nitric oxide (NO) and cyclooxygenase (COX) pathways in OT postconditioning. Isolated rat hearts were divided into10 groups and underwent 30 min of regional ischemia followed by 120 min of reperfusion (n =6). In I/R (ischemia/reperfusion) group, ischemia and reperfusion were induced without any treatment. In OT group, oxytocin was perfused 5 min prior to beginning of reperfusion for 25 min. In groups 3-6, atosiban (oxytocin receptor blocker), L-NAME (N-Nitro-L-Arginine Methyl Ester, non-specific nitric oxide synthase inhibitor), 5-HD (5-hydroxydecanoate, mKATP inhibitor) and indomethacin (cyclooxygenase inhibitor) were infused prior to oxytocin administration. In others, the mentioned inhibitors were perfused prior to ischemia without oxytocin infusion. Infarct size, ventricular hemodynamic, coronary effluent, malondialdehyde (MDA) and lactate dehydrogenase (LDH) were measured at the end of reperfusion. OT perfusion significantly reduced infarct size, MDA and LDH in comparison with IR group. Atosiban, 5HD, L-NAME and indomethacin abolished the postconditioning effect of OT. Perfusion of the inhibitors alone prior to ischemia had no effect on infarct size, hemodynamic parameters, coronary effluent and biochemical markers as compared with I/R group. In conclusion, this study indicates that postconditioning effects of OT are mediated by activation of mKATP and production of NO and Prostaglandins (PGs).
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August 2015

Post-infarct treatment with [Pyr(1)]apelin-13 improves myocardial function by increasing neovascularization and overexpression of angiogenic growth factors in rats.

Eur J Pharmacol 2015 Aug 1;761:101-8. Epub 2015 May 1.

Department of Physiology, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Islamic Republic of Iran.

Ischemic heart disease is the leading cause of mortality in the world. Angiogenesis is important for cardiac repair after myocardial infarction (MI) as restores blood supply to the ischemic myocardium and preserves cardiac function. Apelin is a peptide that has been recently shown to potentiate angiogenesis. The aim of this study was to investigate angiogenic effects of [Pyr(1)]apelin-13 in the rat model of post-MI. Male Wistar rats (n=36) were randomly divided into three groups: (1) sham (2) MI and (3) MI treated with [Pyr(1)]apelin-13 (MI+Apel). MI animals were subjected to 30min left anterior descending coronary artery (LAD) ligation and 14 days of reperfusion. Twenty-four hours after LAD ligation, [Pyr(1)]apelin-13 (10nmol/kg/day) was administered i.p. for 5 days. Hemodynamic functions by catheter introduced into the left ventricle (LV), myocardial fibrosis by Masson׳s trichrome staining, gene expression of vascular endothelial growth factor-A (VEGFA), VEGF receptor-2 (Kdr), Ang-1 (angiopoietin-1), Tie2 (tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2) and eNOS by Real-time polymerase chain reaction (Real-Time PCR) and myocardial angiogenesis by CD31 imunostaining were assessed at day 14 post-MI. Post-infarct treatment with [Pyr(1)]apelin-13 improved LV function and decreased myocardial fibrosis. [Pyr(1)]apelin-13 treatment led to a significant increase in the expression of VEGFA, Kdr, Ang-1, Tie2 and eNOS. Further, treatment with [Pyr(1)]apelin-13 promoted capillary density. [Pyr(1)]apelin-13 has angiogenic and anti-fibrotic activity via formation of new blood vessels and overexpression of VEGFA, Kdr, Ang-1, Tie2 and eNOS in the infarcted myocardium which could in turn repair myocardium and improve LV function.
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http://dx.doi.org/10.1016/j.ejphar.2015.04.034DOI Listing
August 2015

Vasopressin attenuates ischemia-reperfusion injury via reduction of oxidative stress and inhibition of mitochondrial permeability transition pore opening in rat hearts.

Eur J Pharmacol 2015 Aug 17;760:96-102. Epub 2015 Apr 17.

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Aim of this study was to investigate the involvement of the mitochondrial permeability transition pore (MPTP) and oxidative stress in the cardioprotective effect of vasopressin (AVP) on ischemia/reperfusion (I/R) injury. Anesthetized male wistar rats were subjected to regional 30 min ischemia and 120 min reperfusion and randomly divided into nine groups: (1) Control; saline was administered intravenously before ischemia, (2) vasopressin was administrated 10 min prior to ischemia, (3, 4) Atractyloside as MPTP opener, was injected 5 min prior to reperfusion without and with vasopressin, (5, 6) Cyclosporine A as a MPTP closer, was injected 5 min prior to reperfusion without and with vasopressin, (7) mitochondria were isolated from control group and CaCl2 was added as MPTP opener and swelling inducer, (8) isolated mitochondria from Control hearts was incubated with Cyclosporine A before adding the CaCl2 (9) CaCl2 was added to isolated mitochondria from vasopressin group. Infusion of vasopressin decreased infarct size (18.6±1.7% vs. control group 37.6±2.4%), biochemical parameters [LDH (Lactate Dehydrogenase), CK-MB (Creatine Kinase-MB) and MDA (Malondialdehyde) plasma levels, PAB (Prooxidant-antioxidant balance)] compared to control group. Atactyloside suppressed the cardioprotective effect of vasopressin (32.5±1.9% vs. 18.6±1.7%) but administration of the Cyclosporine A without and with vasopressin significantly reduced infarct size to 17.7±4% (P<0.001) and 22.7±3% (P<0.01) respectively, vs. 37.6±2.4% in control group. Also, vasopressin, similar to Cyclosporine A, led to decrease in CaCl2-induced swelling. It seems that vasopressin through antioxidant effect and MPTP inhibition has created a cardioprotection against ischemia/reperfusion injuries.
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http://dx.doi.org/10.1016/j.ejphar.2015.04.006DOI Listing
August 2015

Hypoxia/ischemia a key player in early post stroke seizures: modulation by opioidergic and nitrergic systems.

Eur J Pharmacol 2015 Jan 15;746:6-13. Epub 2014 Nov 15.

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Stroke is a leading cause of death, disability, and socioeconomic loss worldwide. All attempts at pharmacological reduction of the complications of stroke (e.g. post-stroke seizure, and brain׳s vulnerability to hypoxic/ischemic injury) have failed. Endogenous opioids and nitric oxide (NO) overproduction has been documented in brain hypoxia/ischemia (H/I), which can exert pro-convulsive effects. In this study, we aimed to examine the possible involvement of opioidergic and nitrergic pathways in the pathogenesis of post-stroke seizure. H/I was induced by right common carotid ligation and sham-operated mice served as controls. We demonstrated that right common carotid ligation decreases the threshold for clonic seizures induced by pentylenetetrazole (PTZ), a GABA antagonist. Furthermore, pro-convulsive effect of H/I following right common carotid ligation was blocked by naltrexone (NTX) (3mg/kg), NG-Nitro-l-arginine methyl ester (l-NAME) (10mg/kg), and aminoguanidine (AG) (100mg/kg) administration (P<0.001). Interestingly, co-administration of non-effective doses of NTX and l-NAME (1 and 0.5mg/kg, respectively) reverses epileptogenesis of H/I (P<0.001). In the same way, co-administration of non-effective doses of NTX and AG (1 and 5mg/kg, respectively), reverses epileptogenesis of H/I (P<0.001). Indeed, the histological studies performed on mice exposed to H/I confirmed our previous data. These findings suggest hyper-susceptibility to PTZ induced seizure following H/I is mediated by interaction of opioidergic, and iNOS/NO pathways. Therefore, our results identify new pharmacological targets and provide the rationale for a novel strategy to promote recovery after stroke and possibly other brain injuries.
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http://dx.doi.org/10.1016/j.ejphar.2014.11.005DOI Listing
January 2015

Antiepileptic and Antioxidant Effect of Hydroalcoholic Extract of Ferula Assa Foetida Gum on Pentylentetrazole- induced Kindling in Male Mice.

Basic Clin Neurosci 2013 ;4(4):299-306

Department of Physiology. Tehran University of Medical Sciences, Tehran Iran.

Introduction: Considering the prevalence of epilepsy and the failure of available treatments for many epileptic patients, finding more effective drugs in the treatment of epilepsy seems necessary. Oxidative stress has a special role in the pathogenesis of epileptic syndrome. Therefore, in the present study, we have examined the anti-epileptic and anti-oxidant properties of the Ferula Assa Foetida gum extract, using the pentylentetrazole (PTZ) kindling method. In this experimental study, sixty male Albino mice weighing 25-30 g were selected and were randomly divided into 6 groups. 1- the control group, 2- PTZ-kindled mice, 3- positive control group which received valproate (100 mg/kg) as anti-convulsant drug, 4-5 & 6- the groups of kindled mice that pretreated with 25, 50 and 100 mg/kg doses of Ferula Assa Foetida gum extract.

Methods: Kindling has been induced in all groups, except for the control group via 11 PTZ injections (35 mg /kg; ip) every other day for 22 days. In the 24th day, the PTZ challenge dose was injected (75 mg / kg) to all groups except the control group. The intensity of seizures were observed and noted until 30 minutes after PTZ injection. At list, the mice were decapitated and the brains of all the mice were removed.. and their biochemical factors levels including malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) were determined.

Results: Results of this study show that Ferula Assa Foetida gum extract is able to reduce seizure duration and its intensity. In addition, this extract has reduced MDA and NO levels and increased the level of SOD in the brain tissue compared to the PTZ- kindled mice.

Discussion: It can be concluded that Ferula Assa Foetida gum extract, in specific doses, is able to show an anti-epileptic effect because of its antioxidant properties, probably acting through an enzyme activity mechanism.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202581PMC
October 2014

Protective effect of magnesium on renal function in STZ-induced diabetic rats.

J Diabetes Metab Disord 2014 16;13(1):84. Epub 2014 Aug 16.

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Diabetic nephropathy is a serious complication of T1D (type one diabetes mellitus). Persistent hyperglycemia and subsequent hypomagnesemia is believed to develop kidney damage by activation of oxidative stress. We conducted this study to investigate the renoprotective effect of magnesium sulfate (MgSO4) on renal histopathology and oxidative stress in diabetic rats.

Methods: The study included 70 male rats. The animals were divided into seven groups: control (CRL), control receiving MgSO4 (CRL + Mg1 & CRL + Mg8), diabetic (DM1 & DM8) and diabetic receiving MgSO4 (DM + Mg1 & DM + Mg8). Rats were given 20 mg/kg (i.p) Streptozocin (STZ) for 5 consecutive days in (MLD) multiple low doses to induce T1D. At day 10 treatment groups were received MgSO4 (10 g/l) in drinking water, for 1 or 8 weeks. The blood glucose, BUN and creatinine levels were measured. Renal tissue levels of malondialdehyde (MDA) were measured by thiobarbituric acid (TBA) method to evaluate the oxidative stress. Renal histopathology was done using H & E staining method.

Results: Treatment with MgSO4 significantly decreased the blood glucose in DM + Mg1 and DM + Mg8 groups as compared with DM1 and DM8. Magnesium treatment also decreased serum BUN and tissue level of MDA significantly in both short and long term treatment. The body weight loss and kidney weight to body weight ratio was improved by MgSO4. Histological results showed there were no differences between DM and DM + Mg groups.

Conclusion: Our findings showed that diabetic nephropathy is associated with high blood glucose level and oxidative stress (significant increase in MDA level). The renal dysfunction and oxidative stress can be improved by magnesium sulfate administration. It is suggested that protection against development of diabetic nephropathy by MgSO4 treatment involves changes in the blood glucose and oxidative stress.
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http://dx.doi.org/10.1186/s40200-014-0084-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156611PMC
September 2014

Effects of ascorbic acid on sperm motility, viability, acrosome reaction and DNA integrity in teratozoospermic samples.

Iran J Reprod Med 2014 Feb;12(2):103-10

Kashan University of Medical Sciences, Kashan, Iran.

Background: Oxidative stress in teratozoospermic semen samples caused poor assisted reproductive techniques (ART) outcomes. Among antioxidants, ascorbic acid is a naturally occurring free radical scavenger and as such its presence assists various other mechanisms in decreasing numerous disruptive free radical processes.

Objective: The main goal of this study was to evaluate potential protective effects of ascorbic acid supplementation during in vitro culture of teratozoospermic specimens.

Materials And Methods: Teratozoospermic semen samples that collected from 15 volunteers were processed, centrifuged and incubated at 37(o)C until sperm swimmed-up. Supernatant was divided into four groups and incubated at 37(o)C for one hour under different experimental conditions: Control, 10 µm A23187, 600µm ascorbic acid and 10 µm A23187+600 µm ascorbic acid. After incubation sperm motility, viability, acrosome reaction, DNA damage and malondialdehyde levels were evaluated.

Results: Our results indicated that after one hour incubation, ascorbic acid significantly reduced malondialdehyde level in ascorbic acid group (1.4±0.11 nmol/ml) compared to control group (1.58±0.13 nmol/ml) (p<0.001). At the end of incubation, progressive motility and viability in ascorbic acid group (64.5±8.8% and 80.3±6.4%, respectively) were significantly (p<0.05 and p<0.001, respectively) higher than the control group (54.5±6.8% and 70.9±7.3%, respectively). A23187 significantly (p<0.0001) increased acrosome reaction in A23187 group (37.3±5.6%) compared to control group (8.5±3.2%) and this effect of A23187 attenuated by ascorbic acid in ascorbic acid+A23187 group (17.2±4.4%). DNA fragmentation in ascorbic acid group (20±4.1%) was significantly (p<0.001) lower than controls (28.9±4.6%).

Conclusion: In vitro ascorbic acid supplementation during teratozoospermic semen processing for ART could protect teratozoospermic specimens against oxidative stress, and it could improve ART outcome.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009562PMC
February 2014

Post-infarct treatment with [Pyr1]-apelin-13 reduces myocardial damage through reduction of oxidative injury and nitric oxide enhancement in the rat model of myocardial infarction.

Peptides 2013 Aug 29;46:76-82. Epub 2013 May 29.

Department of Physiology, School of Medicine, Tehran University of Medical Science, Tehran, Islamic Republic of Iran.

Apelin is a newly discovered peptide that has been recently shown to have cardioprotective effects in the animal model of myocardial infarction (MI) and ischemia/reperfusion (I/R) injuries. The aim of the present study was to investigate the long term cardioprotective effect of [Pyr1]-apelin-13 in the rat model of MI. Male Wistar rats (n=22) were randomly divided into three groups: (1) sham operated group (2) control MI group and (3) MI treated with apelin (MI-AP group). MI animals were subjected to 30 min of left anterior descending coronary artery (LAD) ligation and 14 days of reperfusion. 24h after LAD ligation, apelin (10 mol/kg/day) was administered i.p. for 5 days. Blood sampling was performed at days 1, 3, 5 and 7 after MI for determination of serum changes of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), malondialdehyde (MDA) and nitric oxide (NO). Myocardial infarct size (IS) and hemodynamic function were also measured at the end of the study at day 14. We found out that post infarct treatment with apelin decreases infarct size, serum levels of LDH, CK-MB and MDA and increases heart rate and serum level of NO in the consecutive days, but there were no significant differences in blood pressure in the MI-AP group in comparison with MI. In conclusion, apelin has long term cardioprotective effects against myocardial infarction through attenuation of cardiac tissue injury and lipid peroxidation and enhancement of NO production.
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http://dx.doi.org/10.1016/j.peptides.2013.05.006DOI Listing
August 2013

Role of central oxytocin in stress-induced cardioprotection in ischemic-reperfused heart model.

J Cardiol 2013 Jan 16;61(1):79-86. Epub 2012 Nov 16.

Department of Physiology, School of Medicine, Gonabad University of Medical Science, Gonabad, Islamic Republic of Iran.

Background And Purpose: There is growing evidence that stress contributes to cardiovascular disease and triggers the release of oxytocin. Moreover previous studies confirmed oxytocin mimics the protection associated with ischemic preconditioning. The present study was aimed to assess the possible cardioprotective effects of the centrally released oxytocin in response to stress and intracerebroventricular (i.c.v.) administration of exogenous oxytocin in ischemic-reperfused isolated rat heart.

Methods And Subjects: Rats were divided in two main groups and all of them were subjected to i.c.v. infusion of vehicle or drugs: unstressed rats [control: vehicle, oxytocin (OT; 100 ng/5 μl), atosiban (ATO; 4.3 μg/5 μl) as oxytocin antagonist, ATO+OT] and stressed rats [St: stress, OT+St, ATO+St]. After anesthesia, hearts were isolated and subjected to 30 min regional ischemia and 60 min reperfusion (IR). Acute stress protocol included swimming for 10 min before anesthesia. Myocardial function, infarct size, coronary flow, ventricular arrhythmia, and biochemical parameters such as creatine kinase and lactate dehydrogenase were measured. Ischemia-induced ventricular arrhythmias were counted during the occlusion period.

Results: The plasma levels of oxytocin and corticosterone were significantly elevated by stress. Unexpectedly hearts of stressed rats showed a marked depression of IR injury compared to control group. I.c.v. infusion of oxytocin mimicked the cardioprotective effects of stress, yet did not elevate plasma oxytocin level. The protective effects of both stress and i.c.v. oxytocin were blocked by i.c.v. oxytocin antagonist.

Conclusions: These findings suggest that i.c.v. infusion of exogenous oxytocin and centrally released endogenous oxytocin in response to stress could play a role in induction of a preconditioning effect in ischemic-reperfused rat heart via brain receptors.
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http://dx.doi.org/10.1016/j.jjcc.2012.08.021DOI Listing
January 2013