Publications by authors named "Alireza Ebrahimzadeh-Bideskan"

49 Publications

Protective effects of selenium on electromagnetic field-induced apoptosis, aromatase P450 activity, and leptin receptor expression in rat testis.

Iran J Basic Med Sci 2021 Mar;24(3):322-330

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: Electromagnetic field (EMF) emitted by mobiles may affect the male reproductive system. Selenium, as an antioxidant, may protect against electromagnetic field-induced tissue damage. Theis study aimed to investigate the effects of selenium on rat testis exposed to electromagnetic fields.

Materials And Methods: Twenty-four male Wistar rats were divided into four groups, namely EM group (2100 MHZ), EM/SE group (2100 MHZ + selenium (0.2 mg/kg), SE group (selenium 0.2 mg/kg), CONT (control group). Serum LH, FSH, testosterone, leptin and aromatase levels, testis weight and volume index, sperm parameters (count and abnormal percent), seminiferous tubule diam¬eters, germinal epithelia thickness, immunoreactivity of leptin receptor and caspase-3 (for apoptotic cells in germinal epithelium) were investigated.

Results: Our results showed that serum LH, FSH, GnRH, testosterone level, sperm count, germinal epithelium thickness, and seminiferous tubule diameter were significantly declined in the EM group compared with the CONT group (<0.05). However, in the EM group, the serum leptin level, sperm abnormality, aromatase enzyme level, apoptotic cells, and leptin receptor were increased compared with the CONT group (<0.05). Furthermore, an increase in sperm count, germinal epithelium thickness, seminiferous diameters, serum LH, FSH, and GnRH, and testosterone levels, and a significant decrease in sperm abnormality, leptin receptor and apoptotic cells in the EM/SE group compared with the EM group were also observed (<0.05).

Conclusion: This study showed that electromagnetic radiation may have detrimental impacts on the male reproductive system, which can be prevented by use of selenium.
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http://dx.doi.org/10.22038/ijbms.2021.45358.10554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087852PMC
March 2021

Grape seed extract effects on hippocampal neurogenesis, synaptogenesis and dark neurons production in old mice. Can this extract improve learning and memory in aged animals?

Nutr Neurosci 2021 May 10:1-11. Epub 2021 May 10.

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: During the elderly, hippocampal neurogenesis and synaptogenesis reduce and dark neurons (DNs) increase, leading to cognitive impairment. It is believed that natural products can protect the neural cells and system by protecting from damages or promoting regeneration. Therefore, the effects of grape seed extract (GSE) on the hippocampus of aged mice were investigated in this study.

Methods: twelve old mice were divided into two groups of control and GSE. Animals in the GSE group received 300 mg/kg of GSE for eight weeks via gavage. At the end of treatment, cognition performance was evaluated by Morris water maze (MWM) and passive avoidance tests. Hippocampal neurogenesis, synaptogenesis and DNs production were evaluated with immunohistochemistry and histological evaluations on 5-micron coronal tissue sections.

Results: The hippocampal mean number of double cortin positive cells (DCX) per unit area, as well as synaptophysin expression in the GSE group, were significantly higher than the control group (< 0.01). The frequency of DNs in the GSE group was lower than the control group (< 0.05). Behavioral tests showed that GSE improves memory and learning performance.

Conclusion: Consuming GSE in the elderly can potentially alleviate the age-related reduction of hippocampal neurogenesis and synaptogenesis. It is also able to decrease hippocampal DNs production and increase memory and learning.
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http://dx.doi.org/10.1080/1028415X.2021.1918983DOI Listing
May 2021

Neuroprotective effects of vitamin C and garlic on glycoconjugates changes of cerebellar cortex in lead-exposed rat offspring.

J Chem Neuroanat 2021 Jul 27;114:101948. Epub 2021 Mar 27.

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

The deteriorating effects of Lead (Pb) on central nervous system (CNS) such as cerebellum has been demonstrated in previous studies. Glycoconjugates with the important role in CNS development may be affected by Pb-exposure. Utilization of antioxidant agents and herbal plants has attracted a great deal of attention on attenuating neurotoxicants-induced damage. Thus, in this study the neuroprotective effects of vitamin C and garlic on content of glycoconjugates of cerebellar cortex in Pb-exposed animals were investigated. Wistar pregnant rats were divided into: control (C), Pb-exposed (Pb) (1500 ppm lead acetate in drinking water), Pb plus vitamin C (Pb + Vit C) (500 mg/kg) intraperitoneally, Pb plus garlic (Pb + G) (1 mL /100 g body weight fresh garlic juice via gavage), Pb plus vitamin C and garlic (Pb + Vit C + G), and sham groups (Sh). Finally, levels of Pb in blood were measured in both rats and offspring on postnatal day 50 (PND50). Also, the cerebellums were removed for measuring Pb-levels and performing lectin histochemistry. Blood and cerebellar Pb-levels were increased in Pb-exposed group compared to control group (P < 0.001), whereas they were decreased significantly in Pb + Vit C, Pb + G, and Pb + Vit C + G groups (P < 0.01). By using MPA, UEA-1, and WGA lectin histochemistry, Pb-exposed group showed weak staining intensity compared to other groups. Besides, significant decrease was observed in the density of lectin-positive neurons of Pb-exposed group compared to the control group (P < 0.001). Moreover, strong staining intensity and high lectin-positive neurons were found in Pb + Vit C, Pb + G and Pb + Vit C + G groups than Pb-exposed group (P < 0.001). The present study revealed that Pb-exposure can result in alteration in the cerebellar glycoconjugates contents and co-administration of vitamin C and garlic could attenuate the adverse effects of Pb. The findings of this study revealed the ameliorating effects of vitamin C and garlic against Pb, suggesting the potential use of vitamin C and garlic as preventive agents in Pb poisoning.
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http://dx.doi.org/10.1016/j.jchemneu.2021.101948DOI Listing
July 2021

trans-Anethole attenuated renal injury and reduced expressions of angiotensin II receptor (AT1R) and TGF-β in streptozotocin-induced diabetic rats.

Biochimie 2021 Jun 23;185:117-127. Epub 2021 Mar 23.

Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Fibrosis is a pathological process in diabetic nephropathy that causes renal failure and dysfunction. Given the known anti-diabetic effects of trans-Anethole (TA), we aimed to investigate its renoprotective and anti-fibrotic effect alone and in combination with losartan in diabetic nephropathy. Male Wistar rats received a single intraperitoneal injection of 65 mg/kg streptozotocin (STZ) for diabetes induction. Diabetic rats were treated orally with saline, TA (80 mg/kg), losartan (Los; 10 mg/kg), or the combination of TA and losartan (TA-Los) daily for five weeks. Renal function was monitored during the study, and renal fibrosis, oxidative stress markers, apoptotic cells, and the expression and localization of AT1R, TGF-β1, and Col-IV were detected in the kidney. Results showed that TA alone and in combination with losartan was able to decrease blood glucose, urea, and creatinine levels and improve kidney function parameters. TA, Los, and TA-Los significantly reduced tubule vascular degeneration, glomerular and tubulointerstitial sclerosis, oxidative stress, and apoptotic cells. Immunohistochemistry analyses showed that TA, losartan, and TA-losartan combination downregulated the AT1R, Col IV, and TGF-β1 expression and distribution in diabetic rat kidneys. Results suggest that TA is able to suppress diabetic nephropathy in rats effectively, probably by decreasing blood glucose levels and downregulating AT1R and TGF-β1 expression.
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http://dx.doi.org/10.1016/j.biochi.2021.03.011DOI Listing
June 2021

Neuroprotective effects of garlic extract on dopaminergic neurons of substantia nigra in a rat model of Parkinson's disease: motor and non-motor outcomes.

Metab Brain Dis 2021 06 3;36(5):927-937. Epub 2021 Mar 3.

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, PO Box 91779-48564, Azadi Sq, Vakilabad Blvd, Mashhad, Iran.

Parkinson's disease (PD) is a common and severe neurodegenerative disorder associated with a selective loss of dopaminergic neurons in substantia nigra pars compacta. The crucial role of oxidative stress and inflammation in PD onset and progression is evident. It has been proven that garlic extract (GE) protects the cells from oxidative stress, inflammation, mitochondrial dysfunction and apoptosis. That is, we aimed to investigate if GE reveals protective features on the preclinical model of PD. The study has been designed to evaluate both preventive (GE administered before 6-OHDA injection) and therapeutic (GE administered after 6-OHDA injection) effects of GE on the animal model. Forty male Wistar rats were divided into 4 groups including control, lesion, treatment I (received GE before 6-OHDA injection) and treatment II (received GE both before and after 6-OHDA injection). At the end of treatment, hanging, rotarod, open field and passive avoidance tests as well as immunohistochemistry were performed to evaluate the neuroprotective effects of garlic against PD. Our immunohistochemistry analysis revealed that the tyrosine hydroxylase positive cells (TH) in GE treated groups were significantly higher (p˂0.001) than the lesion group. The motor deficiency significantly improved in hanging, rotarod, open-field and apomorphine-induced rotational tests. We observed an attenuation in memory impairment induced by PD on GE treated group. Therefore, we found that GE protects dopaminergic neurons in 6-OHDA-induced neurotoxicity and ameliorates movement disorders and behavioral deficits.
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http://dx.doi.org/10.1007/s11011-021-00705-8DOI Listing
June 2021

Histopathological study on neuroapoptotic alterations induced by etomidate in rat hippocampus.

Acta Histochem 2021 Apr 16;123(3):151693. Epub 2021 Feb 16.

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

In human, there is substantial neurogenesis in the hippocampus that is implicated in memory formation and learning. These new-born neurons can be affected by neuropathological conditions. Anesthesia and surgical procedures are associated with postoperative cognitive changes particularly, impaired memory and learning. Therefore, the aim of this study was to evaluate the possible neurodegenerative effects of etomidate in rat hippocampus. Thirty male Wistar rats weighing 250 ± 30 g were randomly divided into 3 groups: 1) Etomidate group; four times 20 mg intraperitoneal injection with 1-h intervals, 2) Control group; the equal volume of normal saline, and 3) Normal group; without any intervention. 6 h after the last injection, the brains were removed and processed according to routine histological methods. TUNEL assay and toluidine blue staining were performed to evaluate neuro-histopathological changes in different regions of hippocampus. Our results showed that the number of TUNEL positive cells and dark neurons (DNs) in etomidate group were significantly higher in the CA1, CA2, CA3, and dentate gyrus (DG) of hippocampus compared with the control and normal groups (p < 0.05). While, there was no significant difference between the various regions of hippocampus in control and normal groups. Our findings showed that etomidate can increase apoptotic cells and dark neurons induction in different regions of hippocampus mainly in DG.
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http://dx.doi.org/10.1016/j.acthis.2021.151693DOI Listing
April 2021

Protective impact of against neural damage in a rat model of pentylenetetrazole (PTZ)-induced seizure.

Avicenna J Phytomed 2020 Nov-Dec;10(6):574-583

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Objective: Based on the previously-declared anticonvulsant properties of (), this study explored the probable effects of on neuronal apoptosis in the hippocampus of a rat model of pentylenetetrazole (PTZ)-induced seizure.

Materials And Methods: 40 male Wistar rats were randomely divided into control (n=8) and experimental (n=32) groups which underwent PTZ injection. A one-week pre-medication with 50 (PTZ-Ext 50) (n=8), 100 (PTZ-Ext 100) (n=8), and 200 (PTZ-Ext 200) (n=8) mg/kg of hydro-alcoholic extract of was performed while one experimental group (PTZ-induced group) (n=8) received only saline during the week before PTZ injection. After provocation of PTZ-induced seizures, the brains underwent tissue processing and TUNEL staining assay for apoptotic cell quantification.

Results: Our findings revealed that PTZ-induced seizures led to apoptosis in neuronal cells of all sub-regions of the hippocampus; yet, only at CA1, CA3 and DG sub-regions of the PTZ-induced group, the difference in the number of apoptotic neuronal cells was significant in comparison with the control group. In addition, pre-medication with the plant extract led to a significant drop in the quantity of apoptotic neurons in these sub-regions in comparison with the PTZ-induced group which received no pre-medication .

Conclusion: The results of this study showed that extract exerts neuro-protective effects on PTZ-induced seizure.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711291PMC
December 2020

The effect of PEGylated iron oxide nanoparticles on sheep ovarian tissue: An ex-vivo nanosafety study.

Heliyon 2020 Sep 6;6(9):e04862. Epub 2020 Sep 6.

Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Today, nanotechnology plays an important role in our ever-continuous quest to improve the quality of human life. Because of their infinitesimal size, nanostructures can actively interact and alter cellular functions. Therefore, while the clinical benefits of nanotechnology may outweigh most of the associated risks, assessment of the cytotoxicity of nanostructures in respect to cells and tissues early in product development processes is of great significance. To the best of our knowledge, no such assessment has been performed for nanomaterials on the ovarian cortex before. Herein, silica-coated, PEGylated silica-coated, and uncoated iron oxide nanoparticles (IONP) with core diameter of 11 nm (±4.2 nm) were synthesized. The oxidative stress in cultured ovarian tissue exposed to the various IONP was subsequently assessed. The results indicate that among the four groups, uncoated IONP induce the most oxidative stress on the ovarian cortex while tissues treated with PEGylated IONP exhibit no significant change in oxidative stress.
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http://dx.doi.org/10.1016/j.heliyon.2020.e04862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486432PMC
September 2020

A link between nanoparticles and Parkinson's disease. Which nanoparticles are most harmful?

Rev Environ Health 2020 Nov 18;35(4):545-556. Epub 2020 Jul 18.

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Nowadays, different kinds of nanoparticles (NPs) are produced around the world and used in many fields and products. NPs can enter the body and aggregate in the various organs including brain. They can damage neurons, in particular dopaminergic neurons in the substantia nigra (SN) and striatal neurons which their lesion is associated with Parkinson's disease (PD). So, NPs can have a role in PD induction along with other agents and factors. PD is the second most common neurodegenerative disease in the world, and in patients, its symptoms progressively worsen day by day through different pathways including oxidative stress, neuroinflammation, mitochondrial dysfunction, α-synuclein increasing and aggregation, apoptosis and reduction of tyrosine hydroxylase positive cells. Unfortunately, there is no effective treatment for PD. So, prevention of this disease is very important. On the other hand, without having sufficient information about PD inducers, prevention of this disease would not be possible. Therefore, we need to have sufficient information about things we contact with them in daily life. Since, NPs are widely used in different products especially in consumer products, and they can enter to the brain easily, in this review the toxicity effects of metal and metal oxide NPs have been evaluated in molecular and cellular levels to determine potential of different kinds of NPs in development of PD.
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http://dx.doi.org/10.1515/reveh-2020-0043DOI Listing
November 2020

Protective effect of crocin on electromagnetic field-induced testicular damage and heat shock protein A2 expression in male BALB/c mice.

Iran J Basic Med Sci 2020 Jan;23(1):102-110

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: Exposure to electromagnetic fields (EMF) emitted from mobile phones may cause a deleterious effect on human health and may affect the male reproductive system. , a carotenoid isolated from , is a phar¬macologically active component of saffron. So, this study was conducted to investigate the protective effect of on the male reproductive system of 60 day old mice after EMF exposure.

Materials And Methods: Twenty-four male BALB/c mice were randomly divided into 4 groups: 1. Em group (2100 MHZ); 2. Cr group (50 mg/kg); 3. Em+Cr group (2100 MHZ+50 mg/kg), and 4. Control group. Sperm parameters (count, and abnormal percent), testis weight index, testis volume, seminiferous tubule diam¬eter, germinal epithelium thickness, LH, FSH and testosterone serum level, testicular Heat shock protein A2 (HspA2) immunoreactivity, and apoptosis were evaluated.

Results: HspA2 immunoreactivity, apoptosis in the germinal epithelium and abnormal sperm were increased in Em group compared with the control group (<0.05). Sperm count, LH, and testosterone serum level were decreased in the Em group compared with the control group (<0.05). These parameters were improved in the Em+Cr group compared with Em group significantly (<0.05).

Conclusion: our findings revealed that EMF exposure leads to harmful impressions on the male reproductive system, while crocin can attenuate EMF-induced destructive effects.
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http://dx.doi.org/10.22038/IJBMS.2019.38896.9229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206838PMC
January 2020

The effect of titanium dioxide nanoparticles on mice midbrain substantia nigra.

Iran J Basic Med Sci 2019 Jul;22(7):745-751

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: Widely used Titanium dioxide nanoparticles (TiO) enter into the body and cause various organ damages. Therefore, we aimed to study the effect of TiO on the substantia nigra of midbrain.

Materials And Methods: 40 male BALB/c mice were randomly divided into five groups: three groups received TiO at doses of 10, 25, and 50 mg/kg, the fourth group received normal saline for 45 days by gavage, and control group (without intervention). Then, Motor tests including pole and hanging tests were done to investigate motor disorders. The animal brain was removed for histological purposes. Accordingly, immunohistochemistry was performed to detect tyrosine hydroxylase positive cells, and then toluidine blue staining was done to identify dark neurons in the substantia nigra. Eventually, the total number of these neurons were counted using stereological methods in different groups.

Results: The results showed that the time recorded for mice to turn completely downward on the pole in the TiO-50 group increased and also the time recorded for animals to hang on the wire in the hanging test significantly decreased (0.05) in comparison with other groups. Also, the average number of tyrosine hydroxylase positive neurons in TiO-25 and TiO-50 groups significantly decreased as compared to the TiO-10 and control groups (0.05). The total number of dark neurons in the TiO-25 and TiO-50 groups was substantially higher than the TiO-10, control and normal saline groups (0.05).

Conclusion: Our findings indicated that TiO, depending on dose, can cause the destruction of dopaminergic neurons and consequently increase the risk of Parkinson's disease.
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http://dx.doi.org/10.22038/ijbms.2019.33611.8018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196354PMC
July 2019

Effects of PPAR-γ agonist, pioglitazone on brain tissues oxidative damage and learning and memory impairment in juvenile hypothyroid rats.

Int J Neurosci 2019 Oct 3;129(10):1024-1038. Epub 2019 Jul 3.

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

: The effect of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone on the brain tissues oxidative damage and learning and memory impairment in the juvenile hypothyroid rats was evaluated. : Rats were classified as: ( 1 ) Control; (2) Propylthiouracil (PTU); (3) PTU-Pio 10 and (4) PTU-Pio 20. PTU was given in drinking water (0.05%) during 6 weeks. Pioglitazone (10 or 20 mg/kg) was daily injected intraperitoneally. Passive avoidance (PA) and Morris water maze (MMW) were conducted. Later, the animals were sacrificed and the brain tissues were removed for biochemical measurements. : The results indicated that in the MWM escape latency as well as traveled path increased in the PTU group as compared to the control group. Also, the time spent in the target quadrant in the probe test of MWM and step-through latency in the PA test were decreased in the PTU group as compared to the control group. Pioglitazone reversed all the negative behavioral effects of hypothyroidism. Administration of PTU attenuated thiol and superoxide dismutase (SOD), and catalase (CAT) activities in the brain tissues, whereas increased malondialdehyde (MDA) and nitric oxide (NO) metabolites. PPARγ agonist improved thiol, SOD and CAT, while diminished MDA concentration. : Our finding in the present study indicated that PPARγ agonist pioglitazone prevented the brain tissues from oxidative damage and learning and memory impairments in juvenile hypothyroid rats.
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http://dx.doi.org/10.1080/00207454.2019.1632843DOI Listing
October 2019

Thymoquinone alleviates renal interstitial fibrosis and kidney dysfunction in rats with unilateral ureteral obstruction.

Phytother Res 2019 Aug 18;33(8):2023-2033. Epub 2019 Jun 18.

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

Unilateral ureteral obstruction (UUO) causes severe renal tubulointerstitial fibrosis. Because of many pharmacologic properties of thymoquinone (TQ), in this study, the effects of TQ against kidney fibrosis and dysfunction were investigated in rats with UUO. Forty male Wistar rats were divided into five groups: Sham operated, UUO, and the animals with UUO treated with losartan, captopril, or TQ. Collagen IV and transforming growth factor (TGF)-β1 expressions, interstitial fibrosis, histological changes, and kidney function were assessed. UUO markedly increased renal expression of TGF-β1 and collagen I and induced interstitial fibrosis (p < .001). Losartan, captopril, or TQ significantly downregulated the expression of these fibrotic markers and interstitial fibrosis (p < .01-p < .001). In UUO group, serum levels of urea and creatinine and protein excretion rate significantly increased, but glomerular filtration rate (GFR) and urine osmolarity showed a significant decrease (p < .001-p < .05). Administration of captopril and TQ caused no significant change in serum urea and protein excretion rate. Unlike losartan and captopril, TQ caused no significant alteration in GFR compared with Day 1. Losartan caused significant increases in serum urea and creatinine but significant decrease in urine osmolarity. TQ could be regarded as a potent therapeutic agent for treatment of UUO-induced kidney fibrosis and dysfunction.
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http://dx.doi.org/10.1002/ptr.6376DOI Listing
August 2019

Evaluation of antitumor effect of oxygen nanobubble water on breast cancer-bearing BALB/c mice.

J Cell Biochem 2019 09 3;120(9):15546-15552. Epub 2019 May 3.

Department of Biology, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran.

Hypoxia is a condition of low oxygen level which poses a common feature of most cancers. In the current study, we investigated effect of water containing oxygen nanobubble (ONB) on tumor growth in breast cancer 4T1-bearing mice during 14-day treatment period. Tumor-bearing mice were randomly divided into three groups (six mice per group), including the ONB group drinking water containing ONB, the air nanobubble (ANB) group drinking water containing ANB, and control group drinking normal water. Tumor weight and size were measured in 2-day interval during 14-day treatment. mRNA expression of p53, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF), and cyclin D/Cdk2 genes were measured in the treated and control mice. After 8, 12, and 14 days of treatment, tumor size in ONB group was significantly decreased by 40.5%, 32.8%, and 28%, respectively, when compared with the control group. In addition, ANB group showed a significant reduction in tumor burden as well. The messenger RNA (mRNA) level of p53 in tumor cells of ONB and ANB group was found to be 36-fold (P = 0.0001) and 33-fold (P = 0.0001) higher than that in the control group, respectively. There was a ninefold increase in mRNA expression of VEGF gene in tumor cells of ANB mice than that in control mice; however, there was no significant changes in ONB group. Expression of HIF gene was significantly lower in tumor cells of ONB and ANB group than in the control group. It is concluded that drinking ONB water has potential to inhibit tumor growth, however more preclinical and proof-of-concept studies are needed to confirm its safety and therapeutic effect.
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http://dx.doi.org/10.1002/jcb.28821DOI Listing
September 2019

Neurotoxic Effects of Stanozolol on Male Rats' Hippocampi: Does Stanozolol cause apoptosis?

Biomol Concepts 2019 Apr 20;10(1):73-81. Epub 2019 Apr 20.

Mashhad University of Medical Sciences, Mashhad, Iran.

Stanozolol is an anabolic-androgenic steroid which is commonly abused by athletes for improved energy, appearance, and physical size. It has been previously shown to cause changes in behaviour and has various physical effects. Studies have previously been conducted on its neurotoxic effect on the central nervous system (CNS), which are typically psychological in nature. This study was performed to investigate the apoptotic effect of stanozolol on different parts of the rat hippocampus. Sixteen male Wistar rats were divided randomly into two groups (experimental and control). The experimental group received subcutaneous injections of stanozolol (5mg/kg/day) for consecutive 28 days, whereas the control group received saline using the same dosing schedule and administration route. After routine procedures, coronal sections of rat brain were stained with Toluidine blue and TUNEL for pre-apoptotic and apoptotic cell detection, respectively. In order to compare groups, the mean number of TUNEL-positive and pre-apoptotic neurons per unit area were calculated and analysed. Histopathological examination revealed that the mean number of pre-apoptotic and apoptotic neurons in the CA1, CA2, CA3 and DG areas of the hippocampus were significantly increased in the stanozolol treated group. In conclusion, stanozolol abuse may induce pre-apoptotic and apoptotic cell formation in different regions of the hippocampus.
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http://dx.doi.org/10.1515/bmc-2019-0009DOI Listing
April 2019

Neuroprotective and long term potentiation improving effects of vitamin E in juvenile hypothyroid rats.

Int J Vitam Nutr Res 2020 Jan 24;90(1-2):156-168. Epub 2019 Apr 24.

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

Protective effects of vitamin E (Vit E) on long term potentiation (LTP) impairment, neuronal apoptosis and increase of nitric oxide (NO) metabolites in the hippocampus of juvenile rats were examined. The rats were grouped (n=13) as: (1) control; (2) hypothyroid (Hypo) and (3) Hypo-Vit E. Propylthiouracil (PTU) was given in drinking water (0.05%) during 6 weeks. Vit E (20 mg/ kg) was daily injected (IP). To evaluate synaptic plasticity, LTP from the CA area of the hippocampus followed by high frequency stimulation to the ipsilateral Schafer collateral pathway was carried out. The cortical and hippocampal tissues were then removed to measure NO metabolites. The brains of 5 animals in each group were removed for apoptosis study. The hypothyroidism status decreased the slope, 10-90% slope and amplitude of field excitatory post synaptic potential (fEPSP) compared to the control group (P<0.01-P<0.001). Injection of Vit E increased the slope, 10-90% slope and amplitude of the fEPSP in the Hypo-Vit E group in comparison to the Hypo group (P<0.05-P<0.01). TUNEL positive neurons and NO metabolites were higher in the hippocampus of the Hypo rats, as compared to those in the hippocampus of the control ones (P<0.001). Treatment of the Hypo rats by Vit E decreased apoptotic neurons (P<0.01-P<0.001) and NO metabolites (P<0.001) in the hippocampus compared to the Hypo rats. The results of the present study showed that Vit E prevented the LTP impairment and neuronal apoptosis in the hippocampus of juvenile hypothyroid rats.
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http://dx.doi.org/10.1024/0300-9831/a000533DOI Listing
January 2020

Renoprotective Effect of Against Proteinuria and Apoptosis Induced by Adriamycin in Rat.

J Pharmacopuncture 2019 Mar 31;22(1):35-40. Epub 2019 Mar 31.

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

Objective: Adriamycin (ADR) is an important anti-cancer drug which can cause renal toxicity. Given the known anti-inflammatory and antioxidant effects of ), the aim of this study was to determine the effects of hydroalcoholic extract of on ADR- induced nephropathy in rats.

Methods: Fifty male Wistar albino rats were randomly divided into 5 groups including: control, ADR (5 mg/kg), ADR + (600 and 1200 mg/kg) and (1200 mg/kg). The animals were treated with extract for 5 consecutive weeks and ADR was intravenously injected on the 7th day of the study. Urine and serum samples were collected on days 0, 14, 21, 28, and 35 for the measurement of serum cholesterol and albumin levels and urine protein excretion rate. At the end of the study, the left kidneys were removed for apoptosis assessment.

Results: Administration of ADR significantly decreased serum albumin level and increased serum cholesterol and urine protein excretion rate as well as, apoptotic cell numbers compared to the control group ( < 0.001) while had no effect on glomerular filtration rate ( > 0.05). Treatment with , in both 600 and 1200 mg/kg doses, increased serum albumin level and decreased serum cholesterol concentration, urine protein excretion rate and as well as the number of apoptotic cell compared to the ADR group ( < 0.001).

Conclusion: Our results showed that the extract effectively protects against ADR- induced nephropathy by reducing kidney apoptosis and improving renal functioning in rats.
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http://dx.doi.org/10.3831/KPI.2019.22.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461299PMC
March 2019

protects against cisplatin-induced renal dysfunction and tissue damage in rats.

Saudi J Kidney Dis Transpl 2018 Sep-Oct;29(5):1057-1064

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

The aim of the present study was to determine the effect of Plantago major (P. major) on cisplatin-induced kidney injury in the rat. Cisplatin was injected on the 6 day of the experiment. Animals were treated with P. major extract (300, 600, and 1200 mg/kg) and Vitamin E for five days before and two weeks after cisplatin administration. Cisplatin caused a significant decrease in glomerular filtration rate (GFR), urine osmolarity, and urinary excretion rate of potassium, but significant increase in the kidney index and histological damage compared with the control group. Administration of Vitamin E and P. major (300 and 600 mg/kg) significantly increased GFR compared to cisplatin group. Furthermore, urine osmolarity in Vitamin E and P. major (600 mg/kg) groups were significantly elevated compared to the cisplatin group. P. major (600 mg/kg) significantly increased the urinary excretion rate of potassium compared with cisplatin group. Furthermore, all doses of P. major and Vitamin E significantly attenuated the percentage of kidney tissue damage compared to the cisplatin group. However, only P. major (600 mg/kg) and Vitamin E treated rats showed a significant reduction in the kidney index. This study revealed that P. major extract in a dose-dependent manner provides protection against renal damage induced by cisplatin.
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http://dx.doi.org/10.4103/1319-2442.243960DOI Listing
November 2019

The effect of crocin on testicular tissue and sperm parameters of mice offspring from mothers exposed to atrazine during pregnancy and lactation periods: An experimental study.

Int J Reprod Biomed 2018 Aug;16(8):519-528

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Atrazine as a herbicide may affect the human's health. Crocin may protect atrazine-induced damages.

Objective: The aim of this study was to evaluate the effects of atrazine on mice testicular tissue and sperm parameters and protective effects of Crocin on probably atrazine-induced damages.

Materials And Methods: in this experimental study, 24 pregnant Balb/c mice were randomly divided to 4 groups: I: Atrazine (10 mg/kg), II: Atrazine-Crocin, III: Crocin (10mg/kg) and IV: Normal saline. Administrations were done daily by gavage during pregnancy and lactation. In the end, two male offspring were randomly selected from every mother and sacrificed respectively on 23 and 75 postnatal days. Then, their epididymides were removed for sperm parameters investigation and their testes were prepared to evaluate apoptosis by means of TUNEL technique.

Results: The mean number of sperms in the atrazine group was lower compared to other groups and increased in the atrazine-crocin group compared with atrazine group significantly (p=0.001). Sperm abnormality was increased in the atrazine group compared with the normal saline group and decreased in the atrazine-crocin group compared with atrazine group significantly (p≤0.001). TUNEL-positive spermatogonia in 23 days old offspring increased significantly in the atrazine group compared with other groups (p=0.03). TUNEL-positive spermatogenic cells in 75 days old offspring was significantly increased in the atrazine group compared with the saline group (p≤0.001).

Conclusion: Atrazine exposure may lead to decrease the number of sperms, increase sperms abnormality, spermatogenic cell apoptosis and height of germinal epithelium. These complications may improve by crocin administration.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163052PMC
August 2018

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

Neuroprotective effect of crocin on substantia nigra in MPTP-induced Parkinson's disease model of mice.

Anat Sci Int 2019 Jan 29;94(1):119-127. Epub 2018 Aug 29.

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Azadi Sq, Vakilabad Blvd, PO Box 91779-48564, Mashhad, Iran.

Parkinson's disease is caused by damage to substantia nigra dopaminergic neurons. Factors such as oxidative stress, inflammatory factors, and acetylcholinesterase activity may induce this disease. On the other hand, crocin-one of the active ingredients of saffron-has anti-oxidant and anti-inflammatory properties. This study was performed to evaluate the protective effect of crocin to decrease dopaminergic neuron damage and Parkinson's disease complications induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A set of 24 male BALB/c Mice were divided randomly into four groups: (1) MPTP group receiving 30 mg/kg MPTP for 5 days; (2) MPTP + crocin group receiving 30 mg/kg MPTP for 5 days and 30 mg/kg crocin for 15 days; (3) NS group receiving normal saline for 5 days; and (4) NSIG group receiving normal saline intraperitoneally for 5 days and also normal saline by gavage for 15 days. After the treatment period, pole and hanging motor tests were performed in all groups. Then, the brains of all the animals were removed and fixed in formalin, prepared according to routine histologic methods and cut into sections of 5 µm thickness. Prepared sections were stained by immunohistochemistry techniques and toluidine blue to detect tyrosine-hydroxylase (TH)-positive neurons and dark neurons, respectively. Finally, the mean number of these cells were calculated by stereological methods and compared with the statistical tests in different groups. The results showed a significant increase in the time taken for the animal to fall from the pole in the MPTP group in comparison with other groups (P < 0.001). The time taken for them to stay on the wire in the hanging test decreased significantly in the MPTP group compared to the other groups (P < 0.001).,while in the MPTP + crocin group, the time to falling decreased (P < 0.05) and the time staying on the wire increased (P < 0.001) compared to the MPTP group. The number of TH-positive neurons in the MPTP group also decreased significantly in comparison with saline and MPTP + crocin groups (P < 0.001). The number of dark neuron sin the MPTP group increased significantly as compared with saline and the MPTP + Crocin groups (P < 0.001). Our results showed that crocin improves MPTP-induced Parkinson's disease complications and decreases cell death in the substantia nigra.
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http://dx.doi.org/10.1007/s12565-018-0457-7DOI Listing
January 2019

Nigella sativa extract is a potent therapeutic agent for renal inflammation, apoptosis, and oxidative stress in a rat model of unilateral ureteral obstruction.

Phytother Res 2018 Nov 2;32(11):2290-2298. Epub 2018 Aug 2.

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

Unilateral ureteral obstruction (UUO) is a well-established experimental model to evaluate renal interstitial fibrosis. Current study is aimed to investigate the effects of Nigella sativa (NS) extract and renin-angiotensin system (RAS) blockade against kidney damage following UUO in rats. In this study, the rats received intraperitoneal injection of losartan (15 mg/kg), captopril (30 mg/kg), and two doses of NS extract (200 and 400 mg/kg) for 18 consecutive days. At the fourth day of the experiment, laparotomy was performed, and the left ureter was ligated. Sham-operated animals received saline as vehicle, and laparotomy without ureteral ligation was done. UUO was associated with significant increase in the expression of renal angiotensin II and monocyte chemoattractant protein-1, concentration of malondialdehyde and tumor necrosis factor-α, and the number of apoptotic cells when compared with sham group. Renal total thiol content and the activity of antioxidant enzymes were significantly reduced as compared with the sham group. However, treatment of obstructed rats with losartan, captopril, and NS extract significantly improved these renal impairments when compared with UUO group. Thus, NS extract, a potent antioxidant and anti-inflammatory herb, is a therapeutic agent to treat the UUO-induced kidney damage comparable with the well-known RAS inhibitors captopril and losartan.
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http://dx.doi.org/10.1002/ptr.6169DOI Listing
November 2018

Doxorubicin-induced renal inflammation in rats: Protective role of .

Avicenna J Phytomed 2018 Mar-Apr;8(2):179-187

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

Objective: The aim of the present study was to evaluate the possible protective effect of () extract against doxorubicin (DXR)-induced renal inflammation in rats.

Materials And Methods: 80 male albino rats were randomly divided into 8 groups as follows: control, DXR, Ext (extract) 600, Ext1200, dexamethasone+DXR, vitamin E+DXR, Ext600+DXR and Ext1200+DXR. Duration of the study was 35 days and DXR was intravenously injected on the 7 day of the experiment. Tumor necrosis factor-alpha (TNF-α) production and monocyte chemoattractant protein-1 (MCP-1) expression levels were assessed in the left kidney. Serum creatinine concentration and osmolarity were determined on the 1, 14, 21, 28 and 35 days of the experiment.

Results: DXR caused a significant increase in renal expression of MCP-1 and TNF-α production compared to control animals. Administration of dexamethasone, vitamin E and extract significantly improved the expression of these inflammatory mediators compared to DXR group. Compared to day 1 in DXR group, serum osmolarity showed a significant increase on days 21, 28 and 35. Also, on these days, serum osmolarity in DXR group was significantly higher than that on the same days in control group. In Vit E+DXR and Ext 1200+DXR groups, there was no significant changes in serum osmolarity among different days of the study. However, in these groups, serum osmolarity on days 21, 28 and 35 showed a significant decrease compared to the same days in DXR group.

Conclusion: Present results suggest that hydroethanolic extract of protected renal tissue against DXR-induced renal inflammation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885332PMC
April 2018

Protection Against Doxorubicin-induced Nephropathy by Plantago major in Rat.

Iran J Kidney Dis 2018 03;12(2):99-106

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

Introduction: Nephropathy is an important side effect of doxorubicin. The aim of the current study was to investigate the protective effect of Plantago major extract against doxorubicin-induced functional and histological damage in rat's kidney.

Materials And Methods: Sixty Albino rats were randomly divided into 6 groups. Doxorubicin, 5 mg/kg, was injected intravenously on the 7th day of the study. Animals were treated with dexamethasone, 0.9 mg/kg, vitamin E, 100 mg/kg, and P major extract, 600 mg/kg and 1200 mg/kg, for 7 days before and 4 weeks after doxorubicin administration. Glomerular filtration rate, urea clearance, and urine glucose concentration were determined on the 1st day and 1, 2, 3 and 4 weeks after doxorubicin injection. Histological changes were also examined and the end of the study.

Results: Doxorubicin caused significant decreases in glomerular filtration rate and urea clearance and significant glycosuria and kidney damage. Urea clearance in the rats treated with P major showed no significant change between different days of the experiment. Administration of dexamethasone, vitamin E, and low- and high-dose P major significantly improved the glycosuria and kidney tissue damage.

Conclusions: These findings suggested that hydroalcoholic extract of P major protected renal tissue against doxorubicin-induced nephropathy. The protective effects of P major on renal lesions associated with doxorubicin may be due to its antioxidant and anti-inflammatory actions.
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March 2018

The effects of tramadol administration on hippocampal cell apoptosis, learning and memory in adult rats and neuroprotective effects of crocin.

Metab Brain Dis 2018 06 22;33(3):907-916. Epub 2018 Feb 22.

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Azadi Sq., Vakilabad Blvd, P.O. Box 91779-48564, Mashhad, Iran.

Tramadol, a frequently used pain reliever drug, present neurotoxic effects associated to cognitive dysfunction. Moreover, crocin has been reported to have neuroprotective effects. The aim of this study was to assess crocin's capacity to protect learning, and memory abilities on tramadol-treated rats. A total of 35 rats were divided into five groups: Control, Saline, tramadol (50 mg/kg), tramadol + crocin(30 mg/kg), crocin groups and treated orally for 28 consecutive days. Morris water maze (MWM) and passive avoidance (PA) tests were done, followed by dissection of the rat's brains for toluidine blue and TUNEL staining. In MWM test, tramadol group spent lower time and traveled shorter distance in the target quadrant (Q1) (P < 0.05). On the other side, the traveled distance in tramadol-crocin group was higher than tramadol (P < 0.05). In PA test, both the delay for entering the dark, and the total time spent in the light compartment decreased in tramadol comparing to the control group (P < 0.05), while it increased in tramadol-crocin compared with the tramadol group (P < 0.05). In tramadol-treated animals, the dark neurons (DNs) and apoptotic cells in CA1, CA3 and DG increased (P < 0.05), while concurrent intake of crocin decreased the number of DNs and apoptotic cells in these areas (P < 0.05). Crocin was able to improve learning and memory of tramadol-treated rats and also decreased DNs and apoptotic cells in the hippocampus. Considering these results, the potential capacity of crocin for decreasing side effects of tramadol on the nervous system is suggested.
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http://dx.doi.org/10.1007/s11011-018-0194-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956046PMC
June 2018

Effects of Human Adipose-derived Stem Cells and Platelet-Rich Plasma on Healing Response of Canine Alveolar Surgical Bone Defects.

Arch Bone Jt Surg 2017 Nov;5(6):406-418

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Due to the known disadvantages of autologous bone grafting, tissue engineering approaches have become an attractive method for ridge augmentation in dentistry. To the best of our knowledge, this is the first study conducted to evaluate the potential therapeutic capacity of PRP-assisted hADSCs seeded on HA/TCP granules on regenerative healing response of canine alveolar surgical bone defects. This could offer a great advantage to alternative approaches of bone tissue healing-induced therapies at clinically chair-side procedures.

Methods: Cylindrical through-and-through defects were drilled in the mandibular plate of 5 mongrel dogs and filled randomly as following: I- autologous crushed mandibular bone, II- no filling material, III- HA/TCP granules in combination with PRP, and IV- PRP-enriched hADSCs seeded on HA/TCP granules. After the completion of an 8-week period of healing, radiographic, histological and histomorphometrical analysis of osteocyte number, newly-formed vessels and marrow spaces were used for evaluation and comparison of the mentioned groups. Furthermore, the buccal side of mandibular alveolar bone of every individual animal was drilled as normal control samples (n=5).

Results: Our results revealed that hADSCs subcultured on HA/TCP granules in combination with PRP significantly promoted bone tissue regeneration as compared with those defects treated only with PRP and HA/TCP granules (<0.05).

Conclusion: In conclusion, our results indicated that application of PRP-assisted hADSCs could induce bone tissue regeneration in canine alveolar bone defects and thus, present a helpful alternative in bone tissue regeneration.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736890PMC
November 2017

The effect of methamphetamine exposure during pregnancy and lactation on hippocampal doublecortin expression, learning and memory of rat offspring.

Anat Sci Int 2018 Jun 24;93(3):351-363. Epub 2017 Nov 24.

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Azadi Sq., Vakilabad Blvd., P.O. Box 91779-48564, Mashhad, Iran.

The aim of this study was to evaluate the effect of methamphetamine (MA) exposure during pregnancy and lactation on doublecortin (DCX) expression in the hippocampus of rat offspring and also on learning/memory. Thirty-five pregnant Wistar rats were randomly divided into seven groups of 5 rats each: three experimental groups, each receiving 5 mg/kg body weight (BW) intraperitoneal (i.p.) injections of MA during pregnancy or/and lactation; three sham groups, each receiving saline injections; one control group, receiving no injection. After the interventions, two male pups (1 and 22 days old) were randomly selected from each mother, sacrificed and their brains subjected to DCX immunohistochemistry. One additional male pup from each mother was randomly selected and maintained for 60 days for testing in the Morris water maze and passive avoidance tests. MA administration during pregnancy was found to have significantly decreased the number of DCX-positive cells in the CA1, CA3 and DG regions of the hippocampus in the 1-day pups (P ≤ 0.05) and to have significantly decreased the number of DCX-positive cells in only two regions of the hippocampus, the CA1 and DG regions, in 22-day old pups. In comparison, exposure to MA during lactation was only associated with a significant decrease in the number of DCX-positive cells in the DG. Exposure to MA during pregnancy had significant impact on the intensity of DCX expression in the hippocampus of 1- and 22-day pups (P ≤ 0.05). There was no significant difference in memory/learning among the study groups. Our results indicate the administration of MA during pregnancy had a greater effect that during the lactation period on DCX expression in the hippocampus of rat offspring.
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http://dx.doi.org/10.1007/s12565-017-0419-5DOI Listing
June 2018

The effect of platelet-rich plasma on human mesenchymal stem cell-induced bone regeneration of canine alveolar defects with calcium phosphate-based scaffolds.

Iran J Basic Med Sci 2017 Oct;20(10):1131-1140

Microanatomy Research Center, School of Medicine, Mashhad Universityof Medical Sciences, Mashhad, Iran.

Objectives: Autologous bone transplantation known as the "gold standard" to reconstruction of osseous defects has known disadvantages. This study was designed to explore the effects of hydroxy-apatite/tricalcium-phosphate (HA/TCP) and platelet-rich plasma (PRP) on the osteogenesis ability of human adipose-derived mesenchymal stem cells (hAdMSCs) and .

Materials And Methods: hAdMSCs were incubated with HA/TCP granules and/or PRP and then, cell proliferation and differentiation was assessed by MTT assay, AZR S staining and SEM examination. , four cylindrical defects were drilled in the mandibular bones of 5 mongrel dogs and divided randomly into the following groups: I-autologous crushed bone, II- no filling material, III- HA/TCP and PRP, IV- PRP-enriched hAdMSCs seeded on HA/TCP granules. Inserted hAdMSCs were labeled to trace their contribution to bone tissue regeneration. Finally, cell tracing and tissue regeneration were evaluated by immunohistochemistry and histomorphometry methods, respectively.

Results: , co-incubation with HA/TCP granules significantly reduced proliferation and osteogenic differentiation ability of hAdMSCs; while PRP application promoted these capacities (<0.05). , PRP-enriched hAdMSCs seeded on HA/TCP granules induced considerable bone formation in osseous defects (<0.05). It was obviously shown that hAdMSCs were incorporated into the newly-formed bone.

Conclusion: Based on this study, application of stem cells could offer a helpful therapeutic tool in bone tissue regeneration. Although inserted hAdMSCs were identifiable throughout the newly-formed bone tissue, their few number could be an indicator of indirect role of hAdMSCs in tissue regeneration.
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http://dx.doi.org/10.22038/IJBMS.2017.9447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673698PMC
October 2017

Effects of MDMA (ecstasy) on apoptosis and heat shock protein (HSP70) expression in adult rat testis.

Toxicol Mech Methods 2018 Mar 5;28(3):219-229. Epub 2017 Nov 5.

a Department of Anatomy and Cell Biology, School of Medicine , Mashhad University of Medical Sciences , Mashhad , Iran.

Background: This study was conducted to investigate the effects of MDMA (3,4-methylenedioxymethamphetamine, ecstasy) on apoptosis and heat shock protein expression in adult rat testis.

Methods: Twenty male rats were divided into four groups, two experimental groups (1 and 2), sham control and control. For 16 consecutive days, the experimental groups 1 and 2 were received 5 and 10 mg/kg intraperitoneal (ip) injection of ecstasy, respectively, and in the sham control group, the only saline was injected. In the control group there was no intervention. Finally, the rat's testes were removed and processed for terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and immunohistochemical techniques.

Results: Both doses of MDMA in experimental groups 1 and 2 significantly increased the mean number of TUNEL-positive cells in the germinal epithelium and Leydig cells (p < 0.05). Also in the experimental groups, the immunoreactivity of heat shock protein 70 (HSP70) significantly increased in the testis (p < 0.05).

Conclusions: The findings revealed that MDMA administration increases the level of immunoreactivity of HSP70 and TUNEL-positive cells in the testicular tissue.
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http://dx.doi.org/10.1080/15376516.2017.1388461DOI Listing
March 2018

Fibroblast Growth Factor Type 1 (FGF1)-Overexpressed Adipose-Derived Mesenchaymal Stem Cells (AD-MSC) Induce Neuroprotection and Functional Recovery in a Rat Stroke Model.

Stem Cell Rev Rep 2017 Oct;13(5):670-685

Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Stroke, as the second most common cause of death, imposes a great financial burden on both the individual and society. Mesenchymal stem cells from rodents have demonstrated efficacy in experimental animal models of stroke due to enhanced neurological recovery. Since FGF1 (fibroblast growth factor 1) displays neuroprotective properties, for the first time, we investigated the effect of acute intravenous administration of FGF1 gene transfected adipose-derived mesenchymal stem cell (AD-MSC) on transient experimental ischemic stroke in rats. Stroke induction was made by transient middle cerebral artery occlusion (tMCAO). 2 × 10 AD-MSC was administrated intravenously 30 min after carotid reperfusion. The ability of technetium-hexamethyl propylene amine oxime (Tc-HMPAO)-labeled AD-MSC to enter into ischemic brain was evaluated 2 h post injection. 24 h post operation, the neurological recovery (rotarod and Roger's tests), the infarct volume (2, 3, 5-triphenyltetrazolium chloride, TTC assay), apoptosis rate (TUNEL assay), and the expression of FGF1 protein (western blotting) in the ischemic hemisphere were assessed. The Tc-HMPAO-labeled AD-MSC could enter into the ischemic brain. Ischemic hemisphere activity was significantly higher than that observed in the contralateral hemisphere (p = 0.002). The administration of AD-MSC resulted in significant improvement of neurological function tests and increased density of FGF1 protein in the peri-infarct area, while the infarct volume and the apoptotic index were significantly decreased, in comparison to the other treated groups. In conclusion, acute intravenous administration of AD-MSC can be a novel and promising candidate approach for the treatment of ischemic stroke.
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http://dx.doi.org/10.1007/s12015-017-9755-zDOI Listing
October 2017