Publications by authors named "Saeed Niazmand"

37 Publications

Human T-Cell Leukemia Virus Type 1 Changes Leukocyte Number and Oxidative Stress in the Lung and Blood of Female BALB/c Mice.

Adv Biomed Res 2021 30;10. Epub 2021 Jan 30.

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

Background: Human T-cell leukemia virus type 1(HTLV-1) infection is likely to induce nonneoplastic inflammatory pulmonary diseases. Therefore, an experimental study was conducted to evaluate the leukocytes' number alteration and oxidative stress in the lung and blood of HTLV-1-infected BALB/c mice, which could be of benefit for the recognition of HTLV-1 mechanism in the induction of pulmonary disorders.

Materials And Methods: Twenty female BALB/c mice were divided into two groups of control and HTLV-1-infected animals. The HTLV-1-infected group was inoculated with 10 MT-2 HTLV-1-infected cells. Two months later, the infection was confirmed using real-time polymerase chain reaction, and then lung pathological changes, total and differential inflammatory cell counts in the blood and bronchoalveolar lavage fluid (BALF), along with oxidative stress biomarker levels in the BALF and lung tissue were evaluated.

Results: In the HTLV-1-infected group, the peribronchitis score ( < 0.01), the number of total leukocytes, neutrophils, lymphocytes, and monocytes ( < 0.05) in the blood and BALF were increased. The number of eosinophils in the blood of the HTLV-1-infected group was higher than in the control group ( < 0.01), whereas the number of basophils of BALF was increased in the HTLV-1-infected group ( < 0.001). The lung and BALF oxidative stress results showed that the MDA level was increased, while the total thiol level and superoxide dismutase activity were decreased in the HTLV-1-infected group ( < 0.01).

Conclusion: The HTLV-1 infection seems to induce pulmonary inflammatory reactions by recruiting leukocytes as well as inducing oxidative stress in the lung tissue.
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http://dx.doi.org/10.4103/abr.abr_117_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095261PMC
January 2021

Antihypertensive Effects of Standardized Asafoetida: Effect on Hypertension Induced by Angiotensin II.

Adv Biomed Res 2020 23;9:77. Epub 2020 Dec 23.

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

Background: Asafoetida is an oleo-gum-resin obtained from the rhizome of plant that its effects on hypertension have been reported. This study examines the effect of aqueous extract of asafoetida on the cardiovascular parameters in acute hypertension induced by angiotensin II (AngII).

Materials And Methods: Thirty-six male rats were divided into six groups including Group 1: control; Group 2: AngII (50 ng/kg, intravenous); Group 3: losartan (Los; 10 mg/kg, i. p) + AngII; and Groups 4, 5, and 6 that received three doses of asafoetida (10, 30, and 60 mg/kg, i. p), separately. Los and extract were injected 30 min before hypertension induced by AngII. The femoral artery was cannulated and was connected to a pressure transducer, and cardiovascular parameters (systolic blood pressure [SBP], mean arterial pressure [MAP], and heart rate [HR]) were continuously recorded by a Power Lab system. The changes (Δ) of parameters were calculated and used for statistical analysis.

Results: AngII significantly increased the value of Δ SBP and Δ MAP compared to the control and significantly decreased Δ HR value. Injection of Los attenuated increased cardiovascular responses by AngII. Three doses of asafoetida ameliorated cardiovascular responses by AngII. Three doses of asafoetida decreased the Δ HR non significantly compared to AngII.

Conclusion: Our results indicated that aqueous extract of asafoetida ameliorated cardiovascular responses in acute hypertension induced by AngII. This effect in a lower dose was more effective and comparable with Los. Therefore, a part of antihypertensive effect of asafoetida is mediated through inhibition of the AngII receptor type 1 receptor of AngII.
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http://dx.doi.org/10.4103/abr.abr_106_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059449PMC
December 2020

Cardioprotective effects of Fenugreek () seed extract in streptozotocin induced diabetic rats.

J Cardiovasc Thorac Res 2021 13;13(1):28-36. Epub 2021 Jan 13.

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Inadequate control of diabetes mellitus (DM) leads to considerable cardiovascular implications like diabetic cardiomyopathy (DCM). Cardiomyocyte apoptosis is one of the main mechanisms of DCM pathogenesis associated with hyperglycemia, oxidative stress, inflammation, hyperlipidemia and several other factors. (Fenugreek) has been long used as a traditional medicine and has many therapeutic effects, including anti-diabetic, anti-hyperlipidemia, anti-inflammatory and anti-oxidant properties. The current study aimed to investigate cardioprotective effects of fenugreek seed on diabetic rats. Diabetes was induced in forty-two male rats by injection of streptozotocin (STZ) (60 mg/ kg). Diabetic animals were treated with three different doses of fenugreek seed extract (50, 100 and 200 mg/kg) or metformin (300 mg/kg) for six weeks by gavage. Nondiabetic rats served as controls. Glucose, cholesterol, and triglycerides levels were measured in the blood samples, and oxidative stress markers as well as gene expression of , and were assessed in the cardiac tissues of the experimental groups. Diabetic rats exhibited increased serum glucose, cholesterol and triglycerides levels, elevated markers of oxidative stress thiobarbituric acid-reacting substances (TBARS) levels , total thiol groups (SH), catalase (CAT) and superoxide dismutase (SOD) activity, and enhanced apoptosis cell death (ratio of Bax/Bcl2). Fenugreek seed extract considerably improved metabolism abnormalities, attenuated oxidative stress and diminished apoptosis index. Our study suggests that fenugreek seed may protect the cardiac structure in STZ-induced diabetic rats by attenuating oxidative stress and apoptosis.
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http://dx.doi.org/10.34172/jcvtr.2021.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007891PMC
January 2021

The vasodilatory effect of  L (celery) seed in isolated rat aorta: The roles of endothelium, calcium and potassium channels.

Avicenna J Phytomed 2021 Jan-Feb;11(1):44-53

Department of Health Sciences, McMaster University, Hamilton, Canada.

Objective: (celery) seed has been used for hypertension treatment. To provide a pharmacological basis, the vasorelaxant effect of celery seed extract was investigated in isolated rat aorta.

Materials And Methods: Wistar male rats (200-250 g) were divided into 15 groups (n=7 for each group). The vasorelaxant response of different concentrations of celery seed extract (0.05, 0.1, 0.25, 0.5, 1, and 2 mg/ml) on isolated aorta precontracted with phenylephrine (PE) or KCl was evaluated by organ bath technique. The role of endothelium, extracellular calcium influx, intracellular sources of calcium, and potassium channels in vasorelaxant effect of celery seed extract was investigated.

Results: The extract showed a concentration-dependent relaxation in the isolated aorta contracted with PE and KCl that was endothelium-dependent at lower concentrations. Pretreatment of aortic rings with indomethacin or L-NAME, did not affect the vasorelaxation induced by celery seed extract. The extract inhibited KCl and PE-induced contractions in cumulative calcium concentrations as well as after incubation with diltiazem in denuded aortic rings of endothelium. The relaxation induced by celery seed extract was inhibited by 4-aminopyridine.

Conclusion: This relaxation was mediated by inhibiting calcium influx into vascular smooth muscle cells. Also, voltage-dependent potassium channels were involved in inducing the vasorelaxant effect of celery seed extract.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885007PMC
February 2021

Ginger (Zingiber Officinale Roscoe) Extract Protects the Heart Against Inflammation and Fibrosis in Diabetic Rats.

Can J Diabetes 2021 Apr 2;45(3):220-227. Epub 2020 Sep 2.

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

Background: Fibrosis and inflammation in the heart of patients with diabetes mellitus alongside increased production of free radicals and collagen are together known as diabetic cardiomyopathy. Ginger rhizome has antidiabetic, antioxidant and anti-inflammatory effects. Thus, we investigated the effect of ginger extract on diabetes-induced cardiomyopathy in streptozotocin-induced diabetic rats.

Methods: Animals were divided into 7 groups: control; diabetic; diabetic treated with different doses of ginger extract of 100, 200 and 400 mg/kg; metformin (200 mg/kg); and metformin-valsartan (200 and 30 mg/kg, respectively). Serum levels of glucose, aspartate aminotransferase, lactate dehydrogenase and creatine kinase-muscle/brain were measured. Fibrosis and inflammation were determined by histologic assessment. Gene expression of transforming growth factor (TGF)-β1, TGF-β3 and angiotensin II type 1 receptor was evaluated by real-time polymerase chain reaction in heart tissue.

Results: Serum glucose level in all treated groups, except for the ginger extract 100-mg/kg group, was significantly lower than in the diabetic group. Serum levels of aspartate aminotransferase, lactate dehydrogenase and creatine kinase-muscle/brain were significantly reduced in all treated groups compared with the diabetic group. In the study of fibrosis, collagen amount in the heart tissue of all treated groups, except the ginger extract 100-mg/kg group, was significantly lower than in the diabetic group. Inflammatory cell infiltrates were decreased, and disarrangement was improved in cardiac tissues of all treated groups compared with the diabetic group. Expression of angiotensin II type 1 receptor and TGF-β1 and TGF-β3 genes in all treated groups downregulated compared with the diabetic group.

Conclusions: Treatment by ginger extract reduced myocardial fibrosis and inflammation in the course of diabetic cardiomyopathy, possibly through regulation of the expression of genes involved in the SMAD/TGF-β pathway.
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http://dx.doi.org/10.1016/j.jcjd.2020.08.102DOI Listing
April 2021

Comparing the effects of seed hydro-alcoholic extract, valsartan, and vitamin E on hemodynamic changes, oxidative stress parameters and cardiac hypertrophy in thyrotoxic rats.

Drug Chem Toxicol 2019 Aug 15:1-8. Epub 2019 Aug 15.

d Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences , Mashhad , Iran.

The present study compared the effects of ( seed hydro-alcoholic extract, valsartan, and vitamin E on hemodynamic changes, oxidative stress markers and cardiac hypertrophy in a model of thyrotoxicosis. The hyperthyroid state was induced by intraperitoneal injection of levothyroxine (100 µg/kg) for 4 weeks in male adult rats. After 2 weeks, vitamin E (20 mg/kg), valsartan (8 mg/kg), and seed extract (400 mg/kg) were administered in three groups of thyrotoxic rats. The control group was given a daily injection of normal saline. Systolic blood pressure and heart rate were measured on three occasions with tail cuff. At the end of the fourth week, the animals were scarified and serum samples and heart tissue were collected for biochemical and histological studies. The levothyroxine increased heart rate and systolic blood pressure. A lower heart rate and reduced systolic blood pressure were observed in groups receiving valsartan and extract. The heart weight/body weight ratio increased in groups treated with levothyroxine, but in a microscopic study, cardiomyocyte width was not different between the groups. Levothyroxine increased the level of malondyaldehide and NO metabolite but reduced the thiol concentration, superoxide dismutase, and catalase activities. However, treatment with vitamin E and extract increased the thiol concentration, superoxide dismutase and catalase activities while decreasing malondyaldehide level. In addition, treatment with extract and valsartan decreased NO metabolite level. Treatment with extract improved levothyroxine induced oxidative stress and hemodynamic changes. These effects may be for antioxidant components.
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http://dx.doi.org/10.1080/01480545.2019.1651330DOI Listing
August 2019

The Protective Effects of Pharmacologic Postconditioning of Hydroalcoholic Extract of Nigella sativa on Functional Activities and Oxidative Stress Injury During Ischemia-Reperfusion in Isolated Rat Heart.

Cardiovasc Toxicol 2020 04;20(2):130-138

Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, 9177948564, Iran.

Oxidative stress is known to act as the trigger of cardiac damage during ischemia-reperfusion (I/R) injury. Postconditioning (PoC) is employed to minimize the consequences of ischemia at the onset of reperfusion. Regarding the well-known antioxidant properties of Nigella sativa (Ns), the aim of this study was to investigate whether Nigella sativa postconditioning (Ns-PoC) could reduce IRI by lowering the formation of reactive oxygen species (ROS). Isolated rat hearts were perfused with the Langendorff apparatus, which were subjected to 20 min of preperfusion, 20 min of global ischemia, followed by 40 min of reperfusion. At the onset of reperfusion, based on the type of intervention group, a 10-min period of Krebs flow was developed along with the treatment, and then the reperfusion with Krebs solution was conducted for 30 min. Heart rate (HR) and left ventricular pressure (LVP) were recorded by isometric transducers connected to a data acquisition system. Thiobarbituric acid reactive substances (TBARS), 4-hydroxynonenal (4-HNE) levels, total thiol groups (-SH) levels, superoxide anion dismutase (SOD), and catalase (CAT) activities in myocardial tissues were detected to evaluate the oxidative stress damage degree. Ns-PoC significantly improved cardiodynamic parameters including left ventricular developed pressure (LVDP), rate pressure product (RPP), and the maximum up/down rate of the left ventricular pressure (± dp/dt) as well as SH groups, SOD, and CAT activities. Moreover, it decreased MDA and 4-HNE levels during early reperfusion. The results of this study showed that Ns-PoC ameliorated cardiac functions in isolated rat heart during I/R injuries by improving myocardial oxidative stress states, which may be related to the antioxidant effect of Ns.
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http://dx.doi.org/10.1007/s12012-019-09540-xDOI Listing
April 2020

Trigonella foenum-graceum seed (Fenugreek) hydroalcoholic extract improved the oxidative stress status in a rat model of diabetes-induced memory impairment.

Horm Mol Biol Clin Investig 2019 Jun 6;39(2). Epub 2019 Jun 6.

Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background The antidiabetic and antioxidant effects of Trigonella foenum-graceum have been suggested. The effects of hydroalcoholic extract of the plant seeds and metformin against the diabetes-induced memory impairment were investigated. Materials and methods The rats were treated: (1) control, (2) diabetic (3-6) and diabetic rats treated by 50, 100 and 200 mg/kg of the plant extract or metformin. The rats were diabetic by streptozotocin (STZ, 55 mg/kg). After the passive avoidance test, malondialdehyde (MDA), nitric oxide (NO) metabolites, total thiol (SH), catalase (CAT) and superoxide dismutase (SOD) were determined in the brain. Results In the diabetic group, at 3, 24 and 48 h after receiving a shock, the latency to enter the dark room was lower than for the controls (p < 0.001). All doses of the extract and metformin increased the latencies to enter the dark at 3 and 24 h after the shock treatment (p < 0.05-p < 0.001). Additionally, the two higher doses of the extract and metformin increased the latency at 48 h after the shock (p < 0.05-p < 0.001). Diabetes also elevated MDA and NO metabolites, while it reduced thiol, SOD and CAT in the hippocampal and cortical tissues (p < 0.001). Treatment of the diabetic animals by the highest dose of the extract and also metformin reduced the MDA and NO metabolites, while it improved thiols, SOD and CAT (p < 0.01-p < 0.001). Conclusions Based on our findings, metformin and the hydro-alcoholic extract from the T. foenum-graceum seed prevented memory deficits resulting from diabetes. Preventing oxidative damage in the brain may at least, in part, be responsible for the positive effects of the extract and metformin.
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http://dx.doi.org/10.1515/hmbci-2018-0074DOI Listing
June 2019

Comparison of the Neuroprotective Effects of Aspirin, Atorvastatin, Captopril and Metformin in Diabetes Mellitus.

Biomolecules 2019 03 27;9(4). Epub 2019 Mar 27.

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran.

Objective: The aim of this study was to investigate the effect of combined intake of a high dose of aspirin, atorvastatin, captopril and metformin on oxidative stress in the brain cortex and hippocampus of streptozotocin (STZ)-induced diabetic rats.

Material And Methods: Rats were randomly divided into the following 11 groups: control and diabetic (D), as well as 9 groups that were treated with metformin (M, 300 mg/kg) or aspirin (ASA, 120 mg/kg) alone or in different combinations with captopril (C, 50 mg/kg) and/or atorvastatin (AT, 40 mg/kg) as follows: (D + M), (D + ASA), (D + M + ASA), (D + M + C), (D + M + AT), (D + M + C + ASA), (D + M + C + AT), (D + M + AT + ASA) and (D + M + C + AT + ASA). The rats in treatment groups received drugs by gavage daily for six weeks. Serum lipid profile and levels of oxidative markers in the brain cortex and hippocampus tissues were evaluated.

Results: The levels of malondialdehyde in the brain cortex and hippocampus in all the treated groups decreased significantly ( < 0.05). There was a significant increase in the total thiol concentration as well as catalase activity in treated rats in (M + AT), (M + C + ASA), (M + C + AT), (M + AT + ASA) and (M + C + AT + ASA) groups in cortex and hippocampus in comparison with the diabetic rats ( < 0.05). Also, the superoxide dismutase activity in all treated rats with medications was significantly increased compared to the diabetic rats ( < 0.05⁻0.01).

Conclusion: Our findings showed that the combined use of high-dose aspirin, metformin, captopril and atorvastatin potentiated their antioxidant effects on the brain, and hence could potentially improve cognitive function with their neuroprotective effects on hippocampus.
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http://dx.doi.org/10.3390/biom9040118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523359PMC
March 2019

L. Improves Blood Glucose and Lipids and Ameliorates Oxidative Stress in Heart and Aorta of Diabetic Rats.

Int J Prev Med 2018 24;9:110. Epub 2018 Dec 24.

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

Background: Diabetes mellitus (DM) is a prime risk factor for cardiovascular disease. The convincing experimental and clinical evidence indicated that the onset of DM is closely associated with oxidative stress and that the generation of reactive oxygen species increases in both the types of diabetes. The aim of the present study was to evaluate the effect of (TP) hydroalcoholic extract on the blood glucose, cholesterol, triglyceride, and oxidative stress markers of the heart and aorta in streptozotocin (STZ)-induced diabetic rats.

Methods: The male Wistar rats assigned into six groups ( = 8 in each group): Control, diabetic, and diabetic rats treated with TP extract (100, 200, and 400 mg/kg) or met and metformin (300 mg/kg) formin (300 mg/kg) group, by daily gavage for 6 weeks. Diabetes was induced by injection of STZ (60 mg/kg, i.p). Serum lipids and glucose, malondialdehyde (MDA) level, total thiol level, and also the activities of Cu, Zn-superoxide dismutase (SOD) in the cardiac and aortic tissues were assessed.

Results: TP extract reduced serum glucose, triglyceride and cholesterol. The MDA levels were reduced significantly in all TP-treated groups and metformin. Total thiol levels were improved in the heart and aorta of TP extract-treated groups and metformin compared to the diabetic rats. The activity of SOD in the cardiac and aortic tissues of TP extract- and metformin-treated groups was higher than diabetic group.

Conclusions: The results showed that chronic administration of TP in STZ-induced diabetic rats could decrease blood glucose, cholesterol, and triglyceride and also attenuate the oxidative stress in the aortic and cardiac tissues.
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http://dx.doi.org/10.4103/ijpvm.IJPVM_189_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326021PMC
December 2018

The effects of estradiol and testosterone on renal tissues oxidative after central injection of angiotensin II in female doca - salt treated rats.

Horm Mol Biol Clin Investig 2018 Nov 6;37(3). Epub 2018 Nov 6.

Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran.

Background Although numerous studies have proven that estrogen (Est) has a protective effect on the development of hypertension, more research needs to be done to show its detailed mechanism in a variety of hypertension. The important role of active oxygen species in blood pressure is well defined. We examined whether or not sex hormones change the growth of reactive oxygen species (ROS) ‎in kidneys after central microinjection of angiotensin II (Ang II).‎ Materials and methods Female Wistar rats, 8 weeks old (200 ± 10 g) were used in this study. The animal groups were (1) Sham, (2) Ovariectomy (OVX), (3) Sham-Hypertension (Sham-Hyper), (4) OVX-Hypertension (OVX-Hyper), (5) Sham-Hyper-Est, (6) OVX-Hyper-Est‎;‎ (7) Sham-Hyper-Testosterone (Tst) and (8) OVX-Hyper-Tst. Solutions of 1% NaCl and 0.1 KCl ‎were used and desoxycorticostrone (doca-salt) was injected (45 mg/kg) 3 times a week in Hypertension groups. Estradiol and Tst (2 mg/kg and ‎5 mg/kg‎; daily; subcutaneously) for 4 weeks. Ang II (50 μM, 5 μL) was microinjected by intracerebroventricular ( i.c.v.) infusion and malondialdehyde (MDA) and thiol in the kidneys were measured. Results MDA in the kidneys was increased by Ang II and doca-salt treatments. Both estradiol and Tst decreased the kidney's MDA. The level of thiol was higher in Hyper ‎groups and reversed after treatment with estradiol and Tst. Conclusions Our findings suggest that central effect of Ang II on blood pressure and kidney ‎disease is accompanied with increased levels of oxidative stress in the kidneys. Indeed sex hormones change the ROS level in the kidneys after central ‎microinjection of Ang II.‎‎.
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http://dx.doi.org/10.1515/hmbci-2018-0044DOI Listing
November 2018

L. Improved Heart Function and Inhibited Myocardial Apoptosis in Isolated Rat Heart Following Ischemia-Reperfusion Injury.

J Pharmacopuncture 2018 Sep 30;21(3):159-167. Epub 2018 Sep 30.

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

Objectives: Myocardial reperfusion is the only logical cure for ischemic heart disease. However, ischemic-reperfusion (I/R) injury is one of the underlying factors facilitating and accelerating the apoptosis in the myocardium. This study set to investigate the impact of (TP) hydro-alcoholic extract on I/R induced apoptosis in the isolated rat heart.

Methods: Isolated rat hearts were classified into six groups. The control samples were subjected to 80 min of perfusion with Krebs-Henseleit bicarbonate (KHB) buffer; in control-ischemia group, after primary perfusion (20 min) the hearts were exposed to global ischemia (20 min) and reperfusion (40 min). Pretreated groups were perfused with 500 μM of vitamin C and various TP concentrations (0.5, 1, 2 mg/ml) for 20 min, and then the hearts were exposed to ischemia and reperfusion for 20 min and 40 min, respectively. Cardiodynamic parameters including rate pressure product (RPP), heart rate (HR), the maximum up/down rate of left ventricular pressure (±), left ventricular developed pressure (LVDP), and coronary artery flow (CF) were achieved from Lab Chart software data. The Bax and BCl-2 gene expressions were measured in heart samples.

Results: Hearts treated with TP extract and vit C represented a meaningful improvement in cardiac contractile function and CF. The overexpression of Bcl-2, downregulation of Bax, and improvement of apoptotic index (Bax/Bcl-2) were observed in pretreated TP extract and vit C hearts.

Conclusion: The TP extract was found to ameliorate the cardiac function in the reperfused myocardium. Also, it can hinder apoptotic pathways causing cardioprotection.
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http://dx.doi.org/10.3831/KPI.2018.21.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168185PMC
September 2018

The standardized extract of Nigella sativa and its major ingredient, thymoquinone, ameliorates angiotensin II-induced hypertension in rats.

J Basic Clin Physiol Pharmacol 2018 Dec;30(1):51-58

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background This study investigated the effect of hydroalcoholic extract of Nigella sativa (N. sativa) and its active component, thymoquinone (TQ) on hypertension induced by angiotensin II (AngII), the main product of renin-angiotensin system (RAS). Methods Seven animal groups (n=7 for each group) were used as follows: (1) control, (2) AngII (300 ng/kg), (3) AngII+losartan (Los; 10 mg/kg), (4) TQ (40 mg/kg)+AngII, and (5-7) three doses of N. sativa (200, 400, and 600 mg/kg)+AngII. Los and AngII were injected intravenously; TQ and extracts were injected intraperitoneally. In TQ and N. sativa-treated groups, 30 min after injection of the extract and TQ, AngII was injected. Cardiovascular parameters were recorded by power lab system after cannulation of femoral artery. The maximum changes (∆) of systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) were calculated and used for statistical analysis. Results AngII significantly increased maximal ∆SBP, ∆MAP, and ∆HR compared with the control (p<0.001), and these effects significantly were blunted by Los. TQ and two higher doses (400 and 600 mg/kg) of N. sativa significantly could antagonize effect of AngII on ∆SBP, ∆MAP (p<0.05 to p<0.001). AngII-induced changes of HR are also significantly decreased by TQ and dose 600 mg/kg of extract (p<0.01 and p<0.05, respectively). Conclusions The N. sativa and its component TQ have the beneficial effect on hypertension probably due to attenuation cardiovascular effects of AngII.
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http://dx.doi.org/10.1515/jbcpp-2018-0074DOI Listing
December 2018

HTLV-1 infection-induced motor dysfunction, memory impairment, depression, and brain tissues oxidative damage in female BALB/c mice.

Life Sci 2018 Nov 21;212:9-19. Epub 2018 Sep 21.

Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenesis-inflammation Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Aims: The HTLV-1 infection is associated with a neuro-inflammatory disease. In the present study, the behavioral consequences and brain oxidative damages were evaluated in HTLV-1-infected BALB/c mice.

Material And Methods: 20 female BALB/c mice were divided into two groups comprising control and HTLV-1-infected. The HTLV-1-infected group was inoculated with a 10 MT-2 HTLV-1-infected cell line. Two months later, the behavioral tests were conducted. Finally, oxidative stress was assessed in the cortex and hippocampus tissues.

Key Findings: In the HTLV-1-infected group, running time and latency to fall, travel distance and time spent in the peripheral zone, total crossing number and total traveled distance in open field test, the latency of entrance into the dark compartment in the passive avoidance test, the new object exploration percentage, and discrimination ratio were significantly lower than in the control group. The immobility time, time spent in the dark compartment in passive avoidance test, and total exploration time significantly increased in the HTLV-1-infected group compared to the control group. In the cortical tissue of the HTLV-1 group, the malondialdehyde levels were elevated while the total thiol levels decreased in comparison to the control group. The activity of superoxide dismutase in the cortical and hippocampal tissues, and catalase activity in cortical tissue significantly decreased in the HTLV-1 group in comparison to the control group.

Significance: The HTLV-1 infection seems to induce depression-like behavior, motor dysfunction, disruption in working and fear memory and also oxidative stress in the cortex and hippocampus.
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http://dx.doi.org/10.1016/j.lfs.2018.09.031DOI Listing
November 2018

Nigella sativa L. seed regulated eNOS, VCAM-1 and LOX-1 genes expression and improved vasoreactivity in aorta of diabetic rat.

J Ethnopharmacol 2019 Jan 14;228:142-147. Epub 2018 Sep 14.

Faghihi hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

Ethnopharmacological Relevance: Nigella sativa L. seed has been widely used in traditional medicine for the treatment of diabetes. The major reason for vascular complications in diabetic patients is endothelial dysfunction. However, the impact of N. sativa seed on endothelial dysfunction in diabetes remains unclear.

Aim Of The Study: This study was conducted to evaluate the effect of the hydroalcoholic extract of N. sativa seed on eNOS, VCAM-1, and LOX-1 genes expression and the vasoreactivity of aortic rings to acetylcholine (Ach) in streptozotocin (STZ)-induced diabetic rat.

Materials And Methods: Treated rats received N. sativa seed extract (100, 200, and 400 mg/kg) daily by gavage for 6 weeks. The fasting blood glucose and lipids were measured and atherogenic index of plasma (AIP) was calculated. The endothelium-dependent vasoreactivity responses of isolated aortic rings were evaluated in the presence of cumulative concentrations of Ach (10-10 M). eNOS, VCAM-1, and LOX-1 genes expression in aortic tissue was assessed by using real time polymerase chain reaction (PCR).

Results: Male diabetic Wistar rats treated with N. sativa seed extract for six weeks reduced serum glucose and lipids and improved AIP. The vasorelaxant responses of aortic rings to Ach were markedly improved. N. sativa seed significantly increased eNOS in mRNA expression level and function, while it decreased VCAM-1 and LOX-1 expressions in vascular cells of aortic tissue which assessed only in mRNA level.

Conclusions: The results of this study showed that N. sativa seed more likely, has antidiabetic and antihyperlipidemic properties and improved vasoreactivity, endothelial dysfunction, and vascular inflammation in diabetic rats' aorta.
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http://dx.doi.org/10.1016/j.jep.2018.09.021DOI Listing
January 2019

effects of allogeneic mesenchymal stem cells in a rat model of acute ischemic kidney injury.

Iran J Basic Med Sci 2018 Aug;21(8):824-831

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

Objectives: Renal ischemia-reperfusion injury (IRI) as a severe condition of acute kidney injury (AKI) is the most common clinical problem with high mortality rates of 35-60% deaths in hospital. Mesenchymal stem cells (MSC) due to unique regenerative characteristics are ideal candidates for the treatment of the ischemic injuries. This work is focused on the administration of MSC to IRI-induced AKI Wistar rats and evaluating their significance in AKI treatment.

Material And Methods: Animals underwent surgical procedure and AKI was induced by 40 min bilateral renal pedicle clamping. Immediately after reperfusion, 2×106 rat bone marrow derived MSCs were injected via intra-parenchymal or intra-aortic route.

Results: Animals subjected to AKI after days 1 and 3 showed significant increase in the serum creatinine and blood urea nitrogen (BUN) concentration along with a declined glomerular filtration rate (GFR) when compared with non-ischemic animals. On the other hand, treated animals showed a significant enhanced regeneration as compared to ischemic animals in both administration route groups.

Conclusion: According to the results concluded from the renoprotective effects of MSC in IRI/AKI, MSCs could be considered as promising therapeutic approach for AKI in clinical applications.
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http://dx.doi.org/10.22038/IJBMS.2018.26829.6566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118091PMC
August 2018

A comparison between the effects of seeds extract and valsartan on echocardiographic and hemodynamic parameters in rats with levothyroxine-induced thyrotoxicosis.

Avicenna J Phytomed 2018 May-Jun;8(3):276-285

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

Objective: The aim of the present study was to compare the effects of (Po) seeds extract and those of valsartan on cardiac function in levothyroxine (T)-treated rats.

Materials And Methods: Forty Wistar rats were divided into four groups (n=10): control, levothyroxine (T), T plus valsartan (T-Val) and T plus hydro-alcoholic extract of the seeds (T-Po). Control group received normal saline. Levothyroxine (100µg/kg/day, i.p.) was administered to three other groups for 4 weeks. Valsartan (8 mg/kg/day, orally) and Po seeds extract (400 mg/kg/day, orally) were administered during the last two weeks of treatment period. At the end of the experiment, echocardiographic and hemodynamic parameters were measured and serum free T, T, and T were measured.

Results: Administration of T for 4 weeks significantly increased serum free T levels in T group but elevations of free T levels in T-Val group were not significant. Free T level decreased in T-Po (p<0.01) compared to T group. Heart rate (HR), heart weight (HW), and left ventricular systolic pressure (LVSP) were significantly increased in T group compared to control group while these parameters in the other groups were not significantly different from those of control group. The reduction in HR, HW, and LVSP were more prominent in T-Po group. Ejection fraction (EF) and fraction shortening (FS) were insignificantly decreased in T group compared to control group.

Conclusion: These results showed that treatment of hyperthyroid rats with seeds extract was more effective than valsartan in reducing cardiac changes induced by levothyroxine.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987442PMC
June 2018

Teucrium polium improves endothelial dysfunction by regulating eNOS and VCAM-1 genes expression and vasoreactivity in diabetic rat aorta.

Biomed Pharmacother 2018 Jul 7;103:1526-1530. Epub 2018 May 7.

Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran.

Endothelial dysfunction is the major cause of vascular complications in diabetes. Teucrium polium L. is traditionally used for the production of antidiabetic herbal medicine. The cardiovascular effects of T. polium, has also been reported. As a result of this, the present study was conducted to evaluate the impacts of T. polium hydroalcoholic extract on the vasoreactivity and endothelial nitric oxide synthase (eNOS) and vascular cell adhesion molecule (VCAM)-1 genes expression as well in streptozotocin (STZ)-induced diabetic rat aorta. Male Wistar rats were randomly divided into six groups: control, diabetic, metformin, and three groups of T. polium (TP 100, TP 200, and TP 400). The control and diabetic groups were given normal saline; metformin group was given 300 mg/kg metformin; and T. polium groups were given 100, 200, and 400 mg/kg T. polium extract, daily by gavage for 6 weeks. T. polium extract was found to significantly reduce serum glucose level. It was also observed that metformin and T. polium extract significantly improved vasorelaxant response of aortic rings to acetylcholine (Ach). Real-time polymerase chain reaction (PCR) analysis showed that T. polium and metformin significantly increased eNOS expression, while it decreased VCAM-1 expressions in aortic tissue of diabetic rats. The results showed that T. polium extract could improve endothelial dysfunction by ameliorating the vasoreactivity and regulating eNOS and VCAM-1 gene expressions as well in STZ-induced diabetic rats' aorta.
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http://dx.doi.org/10.1016/j.biopha.2018.04.158DOI Listing
July 2018

Evaluation of nicotinic receptor of pedunculopontine tegmental nucleus in central cardiovascular regulation in anesthetized rat.

Iran J Basic Med Sci 2018 Apr;21(4):376-381

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: Cholinergic neurons are important neurons in the Pedunculopontine tegmental nucleus (PPT). In this study, nicotinic receptor of the PPT in central cardiovascular regulation in the anesthetized rat was evaluated.

Materials And Methods: Saline, acetylcholine (Ach; doses: 90 and 150 nmol), hexamethonium (Hexa; doses: 100 and 300 nmol) and higher doses of Hexa (300 nmol) + Ach (150 nmol) microinjected into the PPT. The femoral artery was cannulated and cardiovascular responses were continuously recorded by a power lab system. After injection of drugs, peak changes of mean arterial pressure (∆MAP), systolic blood pressure (∆SBP) and heart rate (∆HR) calculated and compared with saline group.

Results: The ∆SBP and ∆MAP significantly decreased by two doses of Ach (<0.05 to <0.001) but ∆HR did not change. Two doses 100 (<0.05) and 300 nmol (<0.01) of Hexa significantly increased ∆HR but did not alter the ∆MAP or ∆SBP. Co-injection of Hexa + Ach significantly strengthened the ∆HR induced by Hexa alone (<0.01) but did not affect ∆MAP or ∆SBP.

Conclusion: These results indicate that nicotinic receptor of the PPT has an inhibitory effect on ∆HR with no significant effect on ∆MAP or ∆SBP.
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http://dx.doi.org/10.22038/IJBMS.2018.25616.6319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960753PMC
April 2018

Extract from . Protects Rat Heart against Oxidative Stress Induced by Ischemic-reperfusion Injury.

Adv Biomed Res 2018 30;7:15. Epub 2018 Jan 30.

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

Background: The deleterious effect of oxidative stress on myocardial ischemia-reperfusion (I/R) has already been shown in previous studies. Since has anti-oxidative and cardio-protective properties, the aim of this study was to investigate the effects of this plant on I/R injuries in the isolated rat heart.

Materials And Methods: The myocardial I/R injury of rat was created by Langendorff retrograde perfusion technology. The heart was preperfused with Krebs-Henseleit (K-H) solution containing extract for 20 min before 20 min global ischemia, and then the reperfusion with K-H bicarbonate buffer was conducted for 40 min. The left ventricular developed pressure and the maximum up/down rate of the left ventricular pressure (±) were recorded by physiological recorder as the myocardial function. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities in the effluent were measured to determine the myocardial injury degree. Thiobarbituric acid reactive substances (TBARS), total thiol groups (-SH), superoxide anion dismutase (SOD), and catalase (CAT) in myocardial tissue were detected to determine the oxidative stress degree.

Results: The results showed that the pretreatment with significantly enhanced cardiac parameters and the coronary artery flow, decreased the LDH, CK activities, and TBARS level, whereas it increased - SH groups, SOD and CAT activities.

Conclusions: Our findings indicated that could provide protection for heart against the I/R injury which may be related to the improvement of myocardial oxidative stress states.
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http://dx.doi.org/10.4103/abr.abr_218_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812096PMC
January 2018

attenuated oxidative stress in the heart and kidney of hypercholesterolemic rabbits.

Avicenna J Phytomed 2018 Jan-Feb;8(1):63-72

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Objective: Oxidative stress plays a critical role in the development of hypercholesterolemia-induced complications. This study evaluated the effects of aspirin and hydroethanolic extract on oxidative stress in the heart and kidney of hypercholesterolemic rabbits.

Materials And Methods: The antioxidant activity, as well as total phenolic and salicin content of (Sa) extract were assessed by DPPH radical scavenging activity, Folin-Ciocalteu and HPLC methods, respectively. Animals were divided into two groups of control (fed with normal chow), and HD (fed with high cholesterol diet for 6 weeks). Then, hypercholesterolemic animals allocated to the following treatment groups: CHO (received HD), Sa extract (HD plus extract 60 and 120 mg/kg), and aspirin (HD plus aspirin 120 mg/kg) and received the treatments on a daily basis for 6 weeks. MDA, GSH, and nitrite concentrations as well as the activities of SOD and CAT were evaluated in cardiac and kidney tissues.

Results: The scavenging activity, total phenolic content and salicin were 19.1 µg/ml (IC50), 153.75 ± 3.6 mg of gallic acid/g, and 18.03 µg/mg, respectively. In comparison to CHO group, MDA levels were diminished in Sa and ASA groups but GSH levels were improved. NO metabolites increased in the heart of Sa 120 mg/kg group and in the kidney of all Sa and ASA treated groups. SOD activity increased only in the heart of Sa groups and in the kidney of Sa and ASA groups. CAT activity increased in the heart and kidney tissues of all Sa and ASA treated groups.

Conclusion: The results showed extract improved redox homeostasis in heart and kidney tissues of hypercholesterolemic rabbits. The extract antioxidant property may be related to its phenolic content.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784080PMC
January 2018

-induced Vasorelaxation Mediated by Endothelium-dependent and Endothelium-independent Mechanisms in Isolated Rat Thoracic Aorta.

Pharmacognosy Res 2017 Oct-Dec;9(4):372-377

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

Objective: There are some reports on hypotensive and antispasmodic effects of L. () (TP).

Subjects And Methods: The activity of different concentrations of TP extract (1, 2, 4 and 8 mg/ml) was evaluated on contractile responses of isolated aorta to potassium chloride (KCl) and phenylephrine (PE).

Results: The cumulative concentrations of the extract induced a concentration-dependent relaxation in the aorta precontracted by PE and KCl. Extract-induced vasorelaxations in denuded aortic rings precontracted by PE and KCl at lower concentrations were considerably less than intact aortic rings, but this effect was significantly more at concentrations of 4 mg/ml for PE-, 4 and 8 mg/ml for KCl-induced contractions. All the extract concentrations (except 1 mg/ml) significantly relaxed PE-induced contraction in the presence of N-nitro-L-arginine methyl ester. Indomethacin reduced effectively extract-induced vasorelaxation at 1 and 2 mg/ml. The extract reduced PE- and KCl-induced contractions in the presence of cumulative calcium concentrations and after incubation with diltiazem; this vasorelaxant effect of TP was decreased. TP-induced relaxation was inhibited by heparin, ruthenium red, glibenclamide, and tetraethylammonium, but 4-aminopyridine had no effect on TP-induced relaxation.

Conclusion: TP extract has vasorelaxant effect on isolated rat thoracic aorta which mediated by endothelium-dependent and endothelium-independent mechanisms. The relaxation mainly was mediated by inhibition of calcium influx in vascular smooth muscle cells. It seems that the vasorelaxant effect of extract at lower concentrations was mediated by nitric oxide and prostacyclin.

Summary: The vasodilatory effect of L. was mediated by several mechanisms. First: L. inhibited receptor operated ROCC and VDCC. Second: L. also inhibited KATP and KCa channels. Third: L. blocked IP3 receptor and reduced the release of calcium from intracellular source. Forth: L. increased the release on NO and PGI2 from endothelial cells. ROCC: Receptor operated calcium channels, VDCC: Voltage dependent calcium channels, PLC: Phospholipase C, IP3: 1,4,5 triphosphate inositol, IP3R: IP3 receptors, SR: sarcoplasmic reticulum, RYR: ryanodine receptors, K+ATP: ATP-sensitive potassium channel, K+Ca: Calcium-activated potassium channel, cAMP: Cyclic adenosine monophosphate, cGMP: Cyclic guanosine monophosphate, PGI2: Prostaglandin I2, NO: Nitric oxide.
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http://dx.doi.org/10.4103/pr.pr_140_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717790PMC
December 2017

Cardiovascular effects of nitrergic system of the pedunculopontine tegmental nucleus in anesthetized rats.

Iran J Basic Med Sci 2017 Jul;20(7):776-782

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

Objectives: Nitric oxide (NO) is an important neurotransmitter in central nervous system involved in central cardiovascular regulation. The presence of NO in the pedunculopontine tegmental (PPT) nucleus has been shown, but its cardiovascular effect has not been determined. In the present study, the cardiovascular effect of NO in the PPT nucleus was evaluated.

Materials And Methods: After induction of anesthesia, a polyethylene catheter (PE-50) filled with heparinized saline inserted into the femoral artery, and the blood pressure (BP) and heart rate (HR) were continuously recorded. Animals were then placed in a stereotaxic apparatus and maximum changes of mean arterial pressure (∆MAP) and heart rate (∆HR) after microinjection of two doses of N-nitro-L-arginine methyl ester (L-NAME, 30 and 90 nmol), L-arginine (L-Arg 10 and 50 nmol) and sodium nitroprusside (SNP, 9 and 27 nmol) into the PPT were provided and compared with control group (One-way ANOVA).

Results: Both doses of L-NAME significantly increased ∆MAP compared to control (<0.05 and <0.01, respectively). ∆HR only in higher dose (90 nmol) significantly increased compared to control (<0.05). Two doses of L-Arg (10 and 50 nmol/150 nl) had no significant effect on ∆MAP or ∆HR. Higher dose of SNP (27 nmol) significantly decreased ∆MAP (<0.05) and its both doses significantly decreased ∆HR compared to control (<0.05 and <0.001, respectively). Effect of higher dose on ∆HR was significantly higher than the lower dose (<0.05).

Conclusion: Our results show an inhibitory effect of the nitrergic system of the PPT on central cardiovascular system.
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http://dx.doi.org/10.22038/IJBMS.2017.9009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569585PMC
July 2017

Nigella sativa seed decreases endothelial dysfunction in streptozotocin-induced diabetic rat aorta.

Avicenna J Phytomed 2016 Jan-Feb;6(1):67-76

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

Objective: Diabetes is an important risk factor for cardiovascular events. The great percent of morbidity in patients with diabetes is due to endothelial dysfunction. The present study investigated the effects of hydroalcholic extract of Nigella sativa (N. sativa) on contractile and dilatation response of isolated aorta in streptozotocin (STZ)-induced diabetic rat.

Materials And Methods: Rats were divided into six experimental groups (control, untreated STZ-diabetic, and N. sativa hydroalcholic extract or metformin-treated diabetic rats). Treated rats received N. sativa extract (100, 200, and 400 mg/kg) or metformin (300 mg/kg) by gavage, daily for 6 weeks. Isolated rat thoracic rings were mounted in an organ bath system then contractile and dilatation responses induced by phenylephrine (PE), acetylcholine (ACh), potassium chloride (KCl), and sodium nitroprusside (SNP) were evaluated in different situations.

Results: The lower concentrations of N. sativa seed extract (DE 100 and DE 200) and metformin significantly reduced the contractile responses to higher concentrations of PE (10(-6) - 10(-5) M) compared to diabetic group (p<0.05 to p<0.01). The relaxation response to Ach 10(-8) M, was increased in DE 200 and metformin groups compared to diabetic group (p<0.05). The relaxation responses to Ach 10(-7) - 10(-5) M were significantly higher in all treated groups compared to diabetic group (p<0.05 to p<0.001).

Conclusion: Chronic administration of N. sativa seed extract has a significant hypoglycemic effect and improves aortic reactivity to vasoconstrictor and vasodilator agents in STZ-induced diabetic rats.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884219PMC
June 2016

Interaction of central Angiotensin II and estrogen on systolic blood pressure in female DOCA-salt treated rats.

Adv Biomed Res 2016 21;5:78. Epub 2016 Apr 21.

Neurogenic Inflammation Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: There is a probable interaction of central angiotensin II (Ang II) and estrogen (Est) on blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Therefore, in the present study, the interaction between Ang II and Est in ovariectomized (Ovx) and Sham rats that were treated with DOCA- salt was evaluated.

Materials And Methods: The female rats were divided into 10 groups as follows: Sham, Ovx, Sham-DOCA, Ovx-DOCA, Sham-DOCA-estrogen (E), Ovx DOCA-E, Sham-DOCA-losartan (L), Ovx-DOCA-L, Sham-DOCA-L-E, and Ovx-DOCA-L-E. The Est groups received estradiol valerate (2 mg/kg; daily; subcutaneously (s.c)) for four weeks. Following that, several doses of Ang II (0.5, 5, 50, 500, 5000 ng/5 μl) were injected via the intracerebroventricular (i.c.v) route and the changes in systolic blood pressure (SBP) were evaluated. In the losartan groups, 200 μg losartan was injected (i.c.v) 15 minutes after the Ang II injection and the blood pressure was recorded. Treatment by DOCA was performed by removal of one kidney, injection of DOCA (45 mg/kg i.p), and adding of sodium chloride (NaCl) (1%) and potassium chloride (KCl) (0.1%) in the drinking water.

Results: The SBP was increased by Ang II and this effect in DOCA-salt treated rat was higher than in the untreated groups. The effect of Ang II on SBP in groups that were treated with Est and L was lower than that in the DOCA-salt groups. Increase in SBP was strongly attenuated by Ang II in groups that were co-treated with both Est and L compared to the DOCA-treated rats. These results showed that Est significantly attenuated the effect of central Ang II on SBP in the DOCA-salt treated rats.

Conclusion: We suggest that there are interactions between E and Ang II in the control of blood pressure in DOCA-salt treated rats.
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http://dx.doi.org/10.4103/2277-9175.180990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863408PMC
May 2016

The effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in hippocampus of STZ-induced diabetic rats.

Avicenna J Phytomed 2015 Jul-Aug;5(4):333-40

Neurogenic Inflammation Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Objective: Oxidative stress plays an important role in the etiology of diabetic complications. Diabetes impairs hippocampus neurogenesis, synaptic plasticity, and learning. The aim of this study was to investigate the effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in STZ-induced diabetic rats' hippocampus.

Materials And Methods: Diabetes induced by 60 mg/kg STZ, i.p, and the rats were divided into five experimental groups (n=8-10 in each group) including control (received 0.5 ml normal saline), untreated STZ-diabetic (received 0.5 ml normal saline), and treated rats received Nigella sativa extract (200 and 400 mg/kg) or metformin (300 mg/kg) by gavage for 42 days. Serum glucose concentration and body weight as well as hippocampus tissue malondialdehyde and thiol levels were determined by calorimetric assay.

Results: Serum glucose level in the diabetic rats treated with 200 mg/kg Nigella sativa extract at the days 24 and 45 decreased in comparison to untreated diabetic group (p<0.05, p<0.01, respectively). Weight loss was significantly different between metformin and Nigella sativa extract at the dose of 200 and 400 mg/kg (p<0.05). Thiol content of hippocampus increased by 200 mg/kg Nigella sativa extract in comparison to untreated diabetic group (p<0.05). Malondialdehyde content of hippocampus reduced by Nigella sativa extract, 200 mg/kg (p<0.001), 400 mg/kg (p<0.05), and metformin (p<0.05) in comparison to the untreated diabetic group.

Conclusion: The results of the present study showed that hydroalcoholic extract of the Nigella sativa decreased oxidative stress in hippocampus of the STZ-induced diabetic rats. Nigella sativa at the dose of 200 mg/kg was more effective to reduce oxidative stress in hippocampus of rats.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587602PMC
October 2015

The effect of angiotensin-converting enzyme inhibition on inflammatory and angiogenic factors in hypercholesterolemia.

Pharmacol Rep 2015 Oct 22;67(5):837-41. Epub 2015 Jan 22.

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

Background: Renin-angiotensin system (RAS) can be activated during hyperlipidemia. Angiotensin II increases the migration of monocytes, cytokine levels, and gene expressions of VEGF and VCAM-1. With this in mind, the present work attempted to investigate the effect of angiotensin-converting enzyme (ACE) inhibition on VEGF, VCAM-1, and nitric oxide (NO) serum levels in hypercholesterolemic rats.

Methods: Forty male Wistar rats were divided into 4 groups including normal diet+saline injection (control), hypercholesterol diet+saline injection, normal diet+captopril injection, and hypercholesterol diet+captopril injection. Before and after the beginning of the diet and after the treatment, the serum levels of cholesterol, triglycerides, LDL, HDL, and NO were measured. Finally, gene expressions of VCAM-1 and VEGF in the vascular cells from aorta were determined.

Results: Hypercholesterolemic diet increased the serum levels of cholesterol, LDL (p<0.001), triglycerides (p<0.01) and decreased HDL (p<0.001). Captopril caused a reduction in the serum levels of cholesterol, LDL (p<0.001), and triglycerides (p<0.05) as well as an increase in HDL levels (p<0.01). Although the serum levels of NO decreased after hypercholesterolemic diet (p<0.001), no significant change was observed after the treatment. Increased gene expressions of VEGF (p<0.05) and VCAM-1 (p<0.01) in hypercholesterolemia were regressed in captopril treated rats (p<0.01 and p<0.05, respectively).

Conclusion: Captopril, an ACE inhibitor, improves hyperlipidemia and prevents from overexpression of genes for VEGF and VCAM-1, that are implicated in the inflammation and angiogenesis.
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http://dx.doi.org/10.1016/j.pharep.2015.01.008DOI Listing
October 2015

Beneficial Effects of Teucrium polium and Metformin on Diabetes-Induced Memory Impairments and Brain Tissue Oxidative Damage in Rats.

Int J Alzheimers Dis 2015 24;2015:493729. Epub 2015 Feb 24.

Department of Physiology, School of Medicine, North Khorasan University of Medical Sciences, Bojnourd, Iran.

Objective. The effects of hydroalcoholic extract of Teucrium polium and metformin on diabetes-induced memory impairment and brain tissues oxidative damage were investigated. Methods. The rats were divided into: (1) Control, (2) Diabetic, (3) Diabetic-Extract 100 (Dia-Ext 100), (4) Diabetic-Extract 200 (Dia-Ext 200), (5) Diabetic-Extract 400 (Dia-Ext 400), and (6) Diabetic-Metformin (Dia-Met). Groups 3-6 were treated by 100, 200, and 400 mg/kg of the extract or metformin, respectively, for 6 weeks (orally). Results. In passive avoidance test, the latency to enter the dark compartment in Diabetic group was lower than that of Control group (P < 0.01). In Dia-Ext 100, Dia-Ext 200, and Dia-Ext 400 and Metformin groups, the latencies were higher than those of Diabetic group (P < 0.01). Lipid peroxides levels (reported as malondialdehyde, MDA, concentration) in the brain of Diabetic group were higher than Control (P < 0.001). Treatment by all doses of the extract and metformin decreased the MDA concentration (P < 0.01). Conclusions. The results of present study showed that metformin and the hydroalcoholic extract of Teucrium polium prevent diabetes-induced memory deficits in rats. Protection against brain tissues oxidative damage might have a role in the beneficial effects of the extract and metformin.
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http://dx.doi.org/10.1155/2015/493729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354963PMC
March 2015

The Effects of Hydroalchoholic Extract of Teucrium polium L. on Hypertension Induced by Angiotensin II in Rats.

Int J Prev Med 2014 Oct;5(10):1255-60

Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, I. R. Iran.

Background: Antispasmodic and vasorelaxant effects of Teucrium polium L. (TP) were mentioned in former studies, so we attempted to evaluate the eventual preventive effect of TP in an acute experimental model of hypertension induced by angiotensin II (Ang II).

Methods: Forty-eight male Wistar rats were divided randomly into six groups (n = 8); control Group (C), which received only saline, group Ang II; which received Ang II (300 ng/min, IV), group losartan (Los); which received Los (10 mg/kg, IV) before Ang II injection, three groups of TP 100, TP 200, and TP 400; which received different doses of TP extract (100, 200 and 400 mg/kg, IP, respectively) before Ang II application. After cannulation of the femoral artery, mean arterial blood pressure (MAP) and heart rate (HR) was continuously measured and recorded during the experiments. Comparisons were performed using t-test with SPSS software, version 16 (SPSS, Chicago, IL).

Results: MAP and HR in Ang group were significantly higher than the control group (P < 0.001), MAP in group Los significantly was lower than Ang group (P < 0.001) and pretreatment with three doses of TP extract also inhibited increasing of MAP after Ang II injection (P < 0.001). Los also inhibited the increase of HR due to Ang II (P < 0.001), but none of three doses of TP extract had a protective effect on tachycardia induced by Ang II.

Conclusions: It seems TP extract could be effective in preventing of high blood pressure induced by Ang II pathway activation but could not have remarkable efficacy for improving the created tachycardia.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223944PMC
October 2014

The effects of tamoxifen on learning, memory and brain tissues oxidative damage in ovariectomized and naïve female rats.

Adv Biomed Res 2014 21;3:219. Epub 2014 Oct 21.

Neurogenic Inflammation Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Regarding the modulatory effects of tamoxifen (TAM) on the actions of estrogen in the present study, the effects of TAM on learning, memory and brain tissues oxidative damage in ovariectomized (OVX) and naοve female rats was investigated.

Materials And Methods: THE ANIMALS WERE DIVIDED INTO: (1) Sham, (2) OVX, (3) Sham-tamoxifen (Sham-TAM) and (4) ovariectomized-tamoxifen (OVX-TAM). The animals of the Sham-TAM and OVX-TAM groups were treated by TAM (1 mg/kg; 4 weeks).

Results: In Morris water maze, the escape latency in the OVX group was higher than in the Sham group (P < 0.01). The time latency in the animals of OVX-TAM group was lower than that of OVX group (P < 0.01); however, there were no significant differences between the Sham-TAM and Sham groups. In the probe trial, the time spent in target quadrant (Q1) by the animals of OVX group was lower than that of Sham group (P < 0.01). Interestingly, the animals of OVX-TAM group spent more times in target quadrant (Q1) compared with OVX group (P < 0.01). In passive avoidance test, the animals of OVX group had lower latencies to enter the dark compartment compared with the Sham group (P < 0.05). The time latency to enter the dark compartment by animals of OVX-TAM group was higher than in OVX group (P < 0.01). In OVX-TAM group, the total thiol concentration was significantly higher (P < 0.05) and malondialdehyde concentration was lower (P < 0.01) than OVX group.

Conclusions: These results allow us to propose that TAM enhances learning and memory of OVX rats. The possible mechanism may be due to the protective effects against brain tissues oxidative damage.
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http://dx.doi.org/10.4103/2277-9175.143297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219215PMC
November 2014