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Taghi Lashkarboluki

Assistant Professor of Biochemistry

Selected Publications

Bahramzadeh Zoeram, S., Elahdadi Salmani, M., Lashkarbolouki, T., Goudarzi, I. Hippocampal orexin receptor blocking prevented the stress induced social learning and memory deficits (2019) Neurobiology of Learning and Memory, 157, pp. 12-23.

DOI: 10.1016/j.nlm.2018.11.009

Stress as a homeostatic challenge leads to the malfunction of learning and memory processes, namely social learning and memory. The orexin system is involved in stress responses through connections to the hypothalamic-pituitary axis (HPA). In addition, the hippocampus, a structure vulnerable to stress-induced changes, expresses orexin receptors 1 and 2 (OXr1 and OXr2) in various sub-regions. The present study is aimed at assessing the effects of hippocampal orexin receptor blockade on social learning and memory impairments and anxiety development following stress. Male Wistar rats (220–250 g) underwent cannula implantation in the hippocampus. Acute (two mild electric shocks, 5.5 mA) and chronic stresses (ten days of restraint, 6 h daily) were applied with or without injection of orexin receptor antagonists (SB-334867 or TCS OX 29). Sociability and social novelty in animals were assessed in a three-chamber social maze at the end of stress application. Anxiety and exploratory behavior of animals were then examined, with 20 min intervals, using the open field (OF) and elevated plus maze (EPM) tests, respectively. Cisterna Magna cerebro-spinal fluid (CSF) was drained, before sacrifice, for orexin (OX) assay and trunk blood was collected to measure the plasma corticosterone (CRT). Neither the acute nor the chronic stress could affect the sociability. The acute but not chronic stress prevented the animal from sniffing the familiar caged rat in the novelty session, a response which was reversed following the blockade of both OXRs. Furthermore, acute but not chronic stress, led to increased anxiety and immobility behavior which were both impeded by blocking the orexin receptor (OXR). Conversely, OX content in CSF increased due to chronic restraint stress, an effect that was reversed by orexin blockade. Finally, elevated plasma CRT was recorded in response to both acute and chronic stresses. The observed increase in plasma CRT in chronically-stressed rats was abolished following inhibition of OXRs, however a similar effect was not seen in the acute-stress group. Our results identify hippocampal OXRs as potential candidates capable of preventing acute stress-induced impairments of social novelty and anxiety behavior, and chronic stress-induced plasma CRT and CSF orexin, changes. OXR manipulation may improve adaptation to stress pathophysiology. © 2018 Elsevier Inc.

AUTHOR KEYWORDS: Anxiety; Hippocampus; Orexin receptors; Social novelty; Stress

Zavareh, S., Gholizadeh, Z., Lashkarbolouki, T. Evaluation of changes in the expression of Wnt/β-catenin target genes in mouse reproductive tissues during estrous cycle: An experimental study (2018) International Journal of Reproductive BioMedicine, 16 (2), pp. 69-76.

DOI: 10.29252/ijrm.16.2.69

Background: The Wingless-type (Wnt)/β-catenin signaling pathway controls cell homeostasis. Reproductive tissues are dynamic in response to steroidal hormone changes. Steroidal hormones are known to control the Wnt/β-catenin pathway, but their role in reproductive tissues remains unknown. Objective: The present study aims to investigate the expression patterns of Wnt/β- catenin target genes in mouse reproductive tissues during the normal estrous cycle. Materials and Methods: In this experimental study, 16 adult NMRI mice were grouped as proestrus, estrus, metestrus, and diestrus according to vaginal smear and histological evaluation of uterine and ovarian tissues. Uterine horns and ovarian tissues were collected. Reverse transcription quantitative polymerase chain reaction was performed to evaluate the expression of Wnt/β-catenin target genes (Myc2, Ppard, Id2, Birc5, and Ascl2) at different stages of the estrous cycle. Results: The expression levels of Id2, Ascl2, and Pprd in uterine tissue were significantly higher at the proestrus phase than at the other stages. Meanwhile, Birc5 expression in uterine tissue was significantly higher at the metestrus stage than at the other stages. Furthermore, Myc2 expression was significantly higher at the diestrus stage than at the estrus and metestrus stages. In the ovarian tissue, the highest expression of Id2, Ascl2, and Birc5 was detected at the proestrus stage, whereas the highest expression of Myc2 and Ppard was observed at the estrus stage. Conclusion: This study showed that Wnt/β-catenin target genes profiles are different among estrous cycle. It seems that different hormonal profiles during estrous cycles play a key role in the expression pattern of Wnt/β-catenin target genes in ovarian and uterine tissue. © 2018, Research and Clinical Center for Infertitlity. All rights reserved.

AUTHOR KEYWORDS: Beta catenin; Estrous cycle; Mice; Wnt signaling pathway
INDEX KEYWORDS: beta catenin; Wnt protein, adult; animal experiment; animal tissue; Article; controlled study; estrus cycle; female; gene expression; histology; mouse; nonhuman; ovary tissue; reverse transcription polymerase chain reaction; signal transduction; uterus horn; vagina cytology

Koohpeyma, H., Goudarzi, I., Elahdadi Salmani, M., Lashkarbolouki, T., Shabani, M. Postnatal Administration of Homocysteine Induces Cerebellar Damage in Rats: Protective Effect of Folic Acid (2018) Neurotoxicity Research, . Article in Press.

DOI: 10.1007/s12640-018-9979-y

A widely held view suggests that homocysteine (Hcy) can contribute to neurodegeneration through promotion of oxidative stress. There is evidence that homocysteine is toxic to cerebellar Purkinje neurons in vitro; however, in vivo action of Hcy on Purkinje cell has not been investigated so far. Thus, this study was designed to evaluate the Hcy effects on neonatal rat cerebellum and cerebellar oxidative stress. We also evaluated the folic acid effects on biochemical alterations elicited by hyperhomocysteinemia (hHcy) in the cerebellum. Group I received normal saline, group II received Hcy subcutaneously twice a day at 8-h intervals (0.3–0.6 μmol/g body weight), group III received Hcy + folic acid (0.011 μmol/g body weight), and group IV received folic acid on postnatal day (PD) 4 until 25. On day 25, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in the cerebellum and motor cortex were assayed. Malondialdehyde (MDA) levels were also evaluated as a marker of lipid peroxidation. Rotarod and locomotor activity tests were performed in PD 25–27. Our results indicated that administration of Hcy increased plasma, cortical, and cerebellar total Hcy levels; reduced GPx activity; and induced lipid peroxidation in the cerebellum. Hcy impaired performance on the rotarod in rats. However, treatment with folic acid significantly attenuated motor coordination impairment, GPx activity reduction, the lipid peroxidation process, and significantly reduced plasma total Hcy levels. Histological analysis indicated that Hcy could decrease Purkinje cell count and folic acid prevented this toxic effect. We conclude that Hcy can induce neurotoxicity and folic acid has neuroprotective effects against cerebellar Hcy toxicity. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

AUTHOR KEYWORDS: Folic acid; Homocysteine; Oxidative stress; Purkinje cell; Rat

Arzhang, A., Elahdadi Salmani, M., Lashkarbolouki, T., Goudarzi, I. Posterior hypothalamus glutamate infusion decreases pentylenetetrazol-induced seizures of male rats through hippocampal histamine increase (2017) Pharmacology Biochemistry and Behavior, 158, pp. 7-13.

DOI: 10.1016/j.pbb.2017.05.004

Objectives Seizures are epileptic manifestations that are intrinsically modulated through different neurotransmitters and receptor systems. Although glutamate increases excitation and hence seizures, it activates other systems which could potentially terminate seizures. Histamine originates from neurons of the posterior hypothalamus (PH) and can mediate anticonvulsant properties, but the effect of local PH glutamate on hippocampal histamine content is unknown. Therefore, in this study, the effect of PH glutamate and the involvement of hippocampal histamine in pentylenetetrazol (PTZ) induced seizure activity was studied. Materials and methods OX2R antagonist (TCS OX2 29, 40 nmol/1 μl, intra-PH), AMPA/Kainate receptor antagonist (CNQX, 3 mM, intra-PH) and glutamate (1 mM) were injected bilaterally into PH using stereotaxic surgery. The intravenous PTZ infusion model was used to generate behavioral convulsions and the amount of hippocampal histamine content was then measured using a biochemical method. Results Administration of glutamate into PH decreased both seizure stage and the duration of tonic-clonic convulsion (TCC) with increasing TCC latency and hippocampal histamine content. Blocking OX2Rs alone or coinhibition of OX2Rs and AMPA/kainate receptors reversed these effects by increasing both seizure stage and TCC duration, and by decreasing both latency and consequent histamine content. Conclusions Our findings suggest that glutamate administration into PH may control seizures (stages and duration) through increasing the hippocampal histamine content. © 2017 Elsevier Inc.

AUTHOR KEYWORDS: Glutamate receptor; Histamine; Orexin 2 receptor; Posterior hypothalamus; PTZ; Seizure
INDEX KEYWORDS: 6 cyano 7 nitro 2,3 quinoxalinedione; glutamic acid; histamine; pentetrazole; glutamic acid; pentetrazole, adult; animal experiment; animal model; animal tissue; Article; controlled study; drug effect; latent period; male; nonhuman; pentylenetetrazole-induced seizure; posterior hypothalamus; priority journal; rat; rat model; tonic clonic seizure; animal; chemically induced; drug effects; histamine release; hypothalamus; metabolism; pathophysiology; seizure; Wistar rat, Animals; Glutamic Acid; Histamine Release; Hypothalamus; Male; Pentylenetetrazole; Rats; Rats, Wistar; Seizures

Soleimani, E., Goudarzi, I., Abrari, K., Lashkarbolouki, T. Maternal administration of melatonin prevents spatial learning and memory deficits induced by developmental ethanol and lead co-exposure (2017) Physiology and Behavior, 173, pp. 200-208.

DOI: 10.1016/j.physbeh.2017.02.012

Melatonin is a radical scavenger with the ability to remove reactive oxidant species. There is report that co-exposure to lead and ethanol during developmental stages induces learning and memory deficits and oxidative stress. Here, we studied the effect of melatonin, with strong antioxidant properties, on memory deficits induced by lead and ethanol co-exposure and oxidative stress in hippocampus. Pregnant rats in lead and ethanol co-exposure group received lead acetate of 0.2% in distilled drinking water and ethanol (4 g/kg) by oral gavages once daily from the 5th day of gestation until weaning. Rats received 10 mg/kg melatonin by oral gavages. On postnatal days (PD) 30, rats trained with six trials per day for 6 consecutive days in the water maze. On day 37, a probe test was done and oxidative stress markers in the hippocampus were evaluated. Results demonstrated lead and ethanol co-exposed rats exhibited higher escape latency during training trials and reduced time spent in target quadrant, higher escape location latency in probe trial test and had significantly higher malondialdehyde (MDA) levels, significantly lower superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities in the hippocampus. Melatonin treatment could improve memory deficits, antioxidants activity and reduced MDA levels in the hippocampus. We conclude, co-exposure to lead and ethanol impair memory and melatonin can prevent from it by oxidative stress modulation. © 2017 Elsevier Inc.

AUTHOR KEYWORDS: Lead and ethanol co-exposure; Melatonin; Oxidative stress; Rat; Spatial memory
INDEX KEYWORDS: alcohol; catalase; drinking water; glutathione peroxidase; lead; lead acetate; malonaldehyde; melatonin; superoxide dismutase; thiobarbituric acid reactive substance; alcohol; antioxidant; catalase; glutathione peroxidase; lead; melatonin; superoxide dismutase, animal experiment; animal model; antioxidant activity; Article; atomic absorption spectrometry; comparative study; controlled study; female; hippocampus; lipid peroxidation; long term memory; male; memory disorder; Morris water maze test; nonhuman; oxidative stress; priority journal; rat; spatial learning; spatial memory; swimming; visual discrimination; age; analysis of variance; animal; chemically induced; drug administration; drug effects; maternal exposure; maze test; Memory Disorders; metabolism; newborn; pregnancy; spatial learning; Wistar rat, Age Factors; Analysis of Variance; Animals; Animals, Newborn; Antioxidants; Catalase; Drug Administration Schedule; Ethanol; Female; Glutathione Peroxidase; Hippocampus; Lead; Lipid Peroxidation; Male; Maternal Exposure; Maze Learning; Melatonin; Memory Disorders; Pregnancy; Rats; Rats, Wistar; Spatial Learning; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Sarfi, M., Elahdadi Salmani, M., Goudarzi, I., Lashkar Boluki, T., Abrari, K. Evaluating the role of astrocytes on β-estradiol effect on seizures of Pilocarpine epileptic model (2017) European Journal of Pharmacology, 797, pp. 32-38.

DOI: 10.1016/j.ejphar.2017.01.005

Epilepsy with periodic and unpredictable seizures is associated with hippocampal glutamate toxicity and tissue reorganization. Astrocytes play an important role in mediating the neuroprotective effects of estradiol and reducing seizure severity. Accordingly, the protective effects of low and high doses of estradiol on behavioral, astrocytic involvement and neuronal survival aspects of Pilocarpine-induced epilepsy were investigated. Lithium- Pilocarpine (30 mg/kg) model was used to provoke epilepsy. Βeta-estradiol (2,40 μg/µl) was injected subcutaneously from 48 before to 48 h after seizure induction. Behavioral convulsions were then monitored and recorded on the day of induction. Four weeks later, glutamine synthetase (GS) activity and the astrocyte transporter GLT-1 expression of the hippocampus were measured. Moreover, hippocampal glutamate and GABA were evaluated to study excitability changes. Finally, neuronal counting in the hippocampus was also performed using Nissl staining. The latency for generalized clonic (GC) convulsions significantly increased while the rate of GC and death significantly reduced due to β-estradiol treatment. GS activity and GLT-1 expression increased in the groups receiving the high dose of β-estradiol and Pilocarpine. Furthermore, the amount of both GABA and glutamate content decreased due to high dose of estradiol, while only GABA increased in Pilocarpine treated rats. Finally, administration of β-estradiol with low and high doses increased and improved the density of nerve cells. It is concluded that chronic administration β-estradiol has anticonvulsant and neuroprotective properties which are plausibly linked to astrocytic activity. © 2017 Elsevier B.V.

AUTHOR KEYWORDS: Astrocyte; Epilepsy; GLT-1 transporter; Glutamine synthetase; β-estradiol
INDEX KEYWORDS: 4 aminobutyric acid; estradiol; glutamate ammonia ligase; glutamic acid; lithium; pilocarpine; sodium glucose cotransporter 1; estradiol; excitatory amino acid transporter 2; glutamate ammonia ligase; pilocarpine; Slc1a2 protein, rat, animal experiment; animal model; animal tissue; anticonvulsant activity; Article; astrocyte; cell density; chronic drug administration; clonic seizure; controlled study; drug megadose; drug screening; enzyme activity; female; hippocampus; latent period; nerve cell excitability; neuroprotection; nonhuman; protein expression; rat; animal; astrocyte; body weight; chemically induced; disease model; dose response; drug effects; metabolism; nerve cell; pathology; Seizures; Wistar rat, Animals; Astrocytes; Body Weight; Disease Models, Animal; Dose-Response Relationship, Drug; Estradiol; Excitatory Amino Acid Transporter 2; Female; Glutamate-Ammonia Ligase; Hippocampus; Neurons; Pilocarpine; Rats; Rats, Wistar; Seizures
PUBLISHER: Elsevier B.V.

Hosseinzadeh, E., Zavareh, S., Lashkarbolouki, T. Antioxidant properties of coenzyme Q10-pretreated mouse pre-antral follicles derived from vitrified ovaries (2017) Journal of Obstetrics and Gynaecology Research, 43 (1), pp. 140-148.

DOI: 10.1111/jog.13173

Aim: This study evaluated the antioxidant status of pre-antral follicles derived from vitrified ovaries pretreated with coenzyme Q10 (CoQ10). Methods: Mouse pre-antral follicles derived from fresh and vitrified warmed ovarian tissue were cultured with or without CoQ10 (50 μmol/L). Follicular growth, total antioxidant capacity (TAC), malondialdehyde (MDA) level, and superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) activity during cultivation were assessed. Results: The growth rate of the fresh pre-antral follicles was higher compared with the vitrified groups, especially in the CoQ10-treated than non-treated groups. MDA increased while TAC decreased at 96 h of the cultivation period. TAC was higher while MDA was lower in the fresh pre-antral follicles than in the vitrified groups. These rates were higher in the CoQ10-treated than non-treated groups. The vitrified and fresh CoQ10-pretreated groups had significantly higher SOD, GPX, and CAT activity compared with the CoQ10 non-treated groups. Conclusion: CoQ10-supplemented maturation medium can increase antioxidant enzyme activity and decrease lipid peroxidation in cultured pre-antral follicles derived from fresh and vitrified mouse ovaries. © 2016 Japan Society of Obstetrics and Gynecology

AUTHOR KEYWORDS: antioxidant enzyme; coenzyme Q10; ovary; vitrification
INDEX KEYWORDS: catalase; glutathione peroxidase; malonaldehyde; superoxide dismutase; ubidecarenone; antioxidant; catalase; glutathione peroxidase; malonaldehyde; superoxide dismutase; ubidecarenone; ubiquinone, animal cell; animal tissue; Article; controlled study; culture medium; enzyme activity; female; lipid peroxidation; metabolic parameters; mouse; nonhuman; ovary follicle; ovary tissue; total antioxidant capacity; vitrification; analogs and derivatives; animal; drug effects; enzymology; metabolism; ovary follicle, Animals; Antioxidants; Catalase; Female; Glutathione Peroxidase; Malondialdehyde; Mice; Ovarian Follicle; Superoxide Dismutase; Ubiquinone; Vitrification

Kashka, R.H., Zavareh, S., Lashkarbolouki, T. Augmenting effect of vitrification on lipid peroxidation in mouse preantral follicle during cultivation: Modulation by coenzyme Q10 (2016) Systems Biology in Reproductive Medicine, 62 (6), pp. 404-414.

DOI: 10.1080/19396368.2016.1235236

Cryopreservation-induced oxidative stress (OS) may lead to lipid peroxidation, which may be responsible for decreased cell survival rate. Coenzyme Q10 (CoQ10) as a potent antioxidant may improve cell viability by neutralizing OS. In this study, oxidative lipid injury following the vitrification of preantral follicles was investigated. The effects of CoQ10 treatment on the malondialdehyde (MDA) levels, lipid peroxidation products, and activities of enzymatic and nonenzymatic antioxidants of vitrified preantral follicles were also studied. Preantral follicles were isolated from immature mouse ovaries and were vitrified. After warming, these follicles were cultured with or without CoQ10 for four days. The levels of total antioxidant capacity (TAC) and MDA, as well as the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT), were assessed at 0, 24, 48, 72, and 96 hours of culture period. The MDA level in the vitrified preantral follicles was higher than that in the fresh groups. By contrast, the MDA level was significantly lower in the groups with CoQ10 treatment than in those without this treatment during cultivation. The TAC level was higher in the fresh preantral follicles than in the vitrified groups. The rates were also higher in the CoQ10-treated groups than in those without this treatment. The activities of SOD, GPX, and CAT were also significantly higher in the fresh groups than in the vitrified groups, especially in the groups with CoQ10 treatment than in those without this treatment. Lowering the vitrification-induced lipid peroxidation of preantral follicles by CoQ10-supplemented maturation medium may be mediated by increasing SOD, GPX, and CAT activities and TAC level during cultivation. © 2016 Taylor & Francis.

AUTHOR KEYWORDS: Coenzyme Q10; lipid peroxidation; preantral follicles; vitrification
INDEX KEYWORDS: antioxidant; catalase; glutathione peroxidase; lipid peroxide; malonaldehyde; superoxide dismutase; ubidecarenone; antioxidant; catalase; glutathione peroxidase; malonaldehyde; superoxide dismutase; ubidecarenone; ubiquinone, animal cell; antioxidant activity; Article; cell culture; cell maturation; controlled study; enzyme activity; in vitro study; lipid peroxidation; mouse; nonhuman; ovary; ovary follicle; ovary follicle cell; ovary follicle development; ovary follicle fluid; priority journal; total antioxidant capacity; vitrification; warming; analogs and derivatives; animal; drug effects; enzymology; female; metabolism; ovary follicle, Animals; Antioxidants; Catalase; Female; Glutathione Peroxidase; Lipid Peroxidation; Malondialdehyde; Mice; Ovarian Follicle; Superoxide Dismutase; Ubiquinone; Vitrification

Mokhtarpour, M., Elahdadi Salmani, M., Lashkarbolouki, T., Abrari, K., Goudarzi, I. Lateral hypothalamus orexinergic system modulates the stress effect on pentylenetetrazol induced seizures through corticotropin releasing hormone receptor type 1 (2016) Neuropharmacology, 110, pp. 15-24.

DOI: 10.1016/j.neuropharm.2016.07.005

Stress is a trigger factor for seizure initiation which activates hypothalamic pituitary adrenal (HPA) axis as well other brain areas. In this respect, corticotropin releasing hormone (CRH) and lateral hypothalamus (LH) orexinergic system are involved in seizure occurrence. In this study, we investigated the role of LH area and orexin expression in (mediation of) stress effect on pentylenetetrazol (PTZ) -induced seizures with hippocampal involvement. Two mild foot shock stresses were applied to intact and adrenalectomized animals; with or without CRHr1 blocking (NBI 27914) in the LH area. Then, changes in orexin production were evaluated by RT-PCR. Intravenous PTZ infusion (25 mg/ml) -induced convulsions were scored upon modified Racine scale. Finally, hippocampal glutamate and GABA were evaluated to study excitability changes. We demonstrated that the duration and severity of convulsions in stress-induced as well as adrenalectomized group were increased. Plasma corticosterone (CRT) level and orexin mRNA expression were built up in the stress and/or seizure groups. Furthermore, glutamate and GABA content was increased and decreased respectively due to stress and seizures. In contrast, rats receiving CRHr1 inhibitor showed reduced severity and duration of seizures, increased GABA, decreased glutamate and corticosterone and also orexin mRNA compared to the inhibitor free rats. Stress and adrenalectomy induced augmenting effect on seizure severity and duration and the subsequent reduction due to CRHr1 blocking with parallel orexin mRNA changes, indicated the likely involvement of CRH1r induced orexin expression of the LH in gating stress effect on convulsions. © 2016 Elsevier Ltd

AUTHOR KEYWORDS: CRH; HPA axis; Orexin; PTZ; Seizure; Stress
INDEX KEYWORDS: 4 aminobutyric acid; corticosterone; corticotropin releasing factor receptor 1; glutamic acid; messenger RNA; orexin; pentetrazole; 2-methyl-4-(N-propyl-N-cycloproanemethylamino)-5-chloro-6-(2,4,6-trichloranilino)pyrimidine; aniline derivative; corticotropin releasing factor receptor; corticotropin releasing factor receptor 1; orexin; pentetrazole; pyrimidine derivative, adult; animal experiment; animal model; animal tissue; Article; blood level; brain function; brain region; controlled study; disease activity; disease association; disease duration; footshock; gene expression; lateral hypothalamus; male; molecular dynamics; molecular pathology; nonhuman; priority journal; protein determination; protein expression; protein function; rat; reverse transcription polymerase chain reaction; seizure; stress; animal; antagonists and inhibitors; biosynthesis; chemically induced; drug effects; lateral hypothalamus; mental stress; metabolism; prevention and control; psychology; seizure; Wistar rat, Aniline Compounds; Animals; Hypothalamic Area, Lateral; Male; Orexins; Pentylenetetrazole; Pyrimidines; Rats; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone; Seizures; Stress, Psychological

Soleimani, E., Goudarzi, I., Abrari, K., Lashkarbolouki, T. The combined effects of developmental lead and ethanol exposure on hippocampus dependent spatial learning and memory in rats: Role of oxidative stress (2016) Food and Chemical Toxicology, 96, pp. 263-272.

DOI: 10.1016/j.fct.2016.07.009

Either developmental lead or ethanol exposure can impair learning and memory via induction of oxidative stress, which results in neuronal damage. we examined the effect of combined exposure with lead and ethanol on spatial learning and memory in offspring and oxidative stress in hippocampus. Rats were exposed to lead (0.2% in drinking water) or ethanol (4 g/kg) either individually or in combination in 5th day gestation through weaning. On postnatal days (PD) 30, rats were trained with six trials per day for 6 consecutive days in the water maze. On day 37, a probe test was done. Also, oxidative stress markers in the hippocampus were also evaluated. Results demonstrated that lead + ethanol co-exposed rats exhibited higher escape latency during training trials and reduced time spent in target quadrant, higher escape location latency and average proximity in probe trial test. There was significant decrease in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and increase of malondialdehyde (MDA) levels in hippocampus of animals co-exposed to lead and ethanol compared with their individual exposures. We suggest that maternal consumption of ethanol during lead exposure has pronounced detrimental effects on memory, which may be mediated by oxidative stress. © 2016

AUTHOR KEYWORDS: Ethanol; Lead; Oxidative stress; Rat; Spatial memory
INDEX KEYWORDS: alcohol; catalase; glutathione peroxidase; lead; malonaldehyde; superoxide dismutase; alcohol; catalase; drug combination; glutathione peroxidase; lead; malonaldehyde; superoxide dismutase, adult; alcohol consumption; animal experiment; animal tissue; Article; controlled study; developmental toxicity; escape behavior; female; gestation period; hippocampus; latent period; male; memory; nonhuman; oxidative stress; perinatal period; prenatal exposure; rat; spatial learning; animal; developmental disorder; drug combination; drug effects; hippocampus; lead poisoning; maze test; memory; metabolism; oxidative stress; spatial learning; Wistar rat, Animals; Catalase; Developmental Disabilities; Drug Combinations; Ethanol; Glutathione Peroxidase; Hippocampus; Lead; Lead Poisoning; Male; Malondialdehyde; Maze Learning; Memory; Oxidative Stress; Rats; Rats, Wistar; Spatial Learning; Superoxide Dismutase

Bazrgar, M., Goudarzi, I., Lashkarbolouki, T., Elahdadi Salmani, M. Melatonin ameliorates oxidative damage induced by maternal lead exposure in rat pups (2015) Physiology and Behavior, 151, pp. 178-188.

DOI: 10.1016/j.physbeh.2015.06.040

During the particular period of cerebellum development, exposure to lead (Pb) decreases cerebellum growth and can result in selective loss of neurons. The detection and prevention of Pb toxicity is a major international public health priorities. This research study was conducted to evaluate the effects of melatonin, an effective antioxidant and free radical scavenger, on Pb induced neurotoxicity and oxidative stress in the cerebellum. Pb exposure was initiated on gestation day 5 with the addition of daily doses of 0.2% lead acetate to distilled drinking water and continues until weaning. Melatonin (10. mg/kg) was given once daily at the same time. 21. days after birth, several antioxidant enzyme activities including superoxide dismutase (SOD) and glutathione peroxidase (GPx) were assayed. Thiobarbituric acid reactive substance (TBARS) levels were measured as a marker of lipid peroxidation. Rotarod and locomotor activity tests were performed on postnatal days (PDs) 31-33 and a histological study was performed after completion of behavioral measurements on PD 33. The results of the present work demonstrated that Pb could induce lipid peroxidation, increase TBARS levels and decrease GPx and SOD activities in the rat cerebellum. We also observed that Pb impaired performance on the rotarod and locomotor activities of rats. However, treatment with melatonin significantly attenuated the motoric impairment and lipid peroxidation process and restored the levels of antioxidants. Histological analysis indicated that Pb could decrease Purkinje cell count and melatonin prevented this toxic effect. These results suggest that treatment with melatonin can improve motor deficits and oxidative stress by protecting the cerebellum against Pb toxicity. © 2015 Elsevier Inc.

AUTHOR KEYWORDS: Lead acetate; Melatonin; Oxidative stress; Purkinje cell; Rat
INDEX KEYWORDS: glutathione peroxidase; lead; melatonin; scavenger; superoxide dismutase; thiobarbituric acid reactive substance; glutathione peroxidase; lead; melatonin; neuroprotective agent; superoxide dismutase; thiobarbituric acid reactive substance, animal experiment; animal model; animal tissue; Article; cerebellum; controlled study; enzyme activity; experimental locomotor activity test; female; histopathology; lipid peroxidation; male; neuroprotection; neurotoxicity; nonhuman; oxidative stress; pregnancy; priority journal; rat; rotarod test; adverse effects; animal; drug effects; maternal exposure; metabolism; Movement Disorders; oxidative stress; pathology; pathophysiology; prenatal exposure; randomization; Wistar rat, Animals; Cerebellum; Female; Glutathione Peroxidase; Lead; Lipid Peroxidation; Maternal Exposure; Melatonin; Movement Disorders; Neuroprotective Agents; Oxidative Stress; Pregnancy; Prenatal Exposure Delayed Effects; Random Allocation; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Bagheri, F., Goudarzi, I., Lashkarbolouki, T., Elahdadi Salmani, M. Melatonin prevents oxidative damage induced by maternal ethanol administration and reduces homocysteine in the cerebellum of rat pups (2015) Behavioural Brain Research, 287, pp. 215-225.

DOI: 10.1016/j.bbr.2015.03.022

Chronic alcoholism leads to elevated plasma and brain homocysteine (Hcy) levels, as demonstrated by animal experiments. This study was designed to evaluate the alterations in offspring rat cerebellum following increase of plasma Hcy level induced by maternal exposure to ethanol and to investigate the possible protective role of melatonin administration upon cerebellar ethanol-induced neurotoxicity. The adult female rats were divided randomly into 4 groups, including one control and three experimental groups, after vaginal plagues. Group I received normal saline, group II received ethanol (4. g/kg), group III received ethanol. +. melatonin (10. mg/kg) and group IV received melatonin on day 6 of gestation until weaning. 21 days after birth, plasma Hcy level, level of lipid peroxidation, the activities of several antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and levels of bcl-2 and bax mRNA expression in cerebellum were determined. Our results demonstrated that ethanol could induce lipid peroxidation, and decrease antioxidants activities and increase plasma total Hcy level. We also observed that ethanol impaired performance on the rotarod and locomotor activities of rats. However, treatment with melatonin significantly attenuated motoric impairment, the lipid peroxidation process and restored the levels of antioxidant activities and significantly reduced plasma total Hcy levels. Moreover, melatonin reduced bax/bcl-2 ratio in the presence of ethanol. We conclude that these results provide evidence that ethanol neurotoxicity in part is related to increase of plasma Hcy levels and melatonin with reducing of plasma Hcy level has neuroprotective effects against ethanol toxicity in cerebellum. © 2015 Elsevier B.V.

AUTHOR KEYWORDS: Ethanol; Homocysteine; Melatonin; Oxidative stress; Purkinje cell; Rat
INDEX KEYWORDS: alcohol; catalase; glutathione peroxidase; homocysteine; melatonin; messenger RNA; protein Bax; protein bcl 2; sodium chloride; superoxide dismutase; thiobarbituric acid reactive substance; alcohol; Bax protein, rat; catalase; central depressant agent; glutathione peroxidase; homocysteine; melatonin; messenger RNA; neuroprotective agent; protein Bax; protein bcl 2; superoxide dismutase, adult; amino acid blood level; animal experiment; animal model; animal tissue; Article; cerebellum injury; cerebellum vermis; controlled study; drug effect; environmental exposure; enzyme activity; evening dosage; female; lipid peroxidation; locomotion; male; motor dysfunction; neuroprotection; neurotoxicity; nonhuman; oxidative stress; priority journal; protein expression; Purkinje cell; rat; rotarod test; animal; blood; cerebellum; drug effects; growth, development and aging; metabolism; oxidative stress; pathology; physiology; pregnancy; prenatal exposure; prevention and control; randomization; Wistar rat, Animals; bcl-2-Associated X Protein; Catalase; Central Nervous System Depressants; Cerebellum; Ethanol; Female; Glutathione Peroxidase; Homocysteine; Lipid Peroxidation; Locomotion; Melatonin; Neuroprotective Agents; Oxidative Stress; Pregnancy; Prenatal Exposure Delayed Effects; Proto-Oncogene Proteins c-bcl-2; Random Allocation; Rats, Wistar; RNA, Messenger; Superoxide Dismutase

Goudarzi, E., Elahdadi Salmani, M., Lashkarbolouki, T., Goudarzi, I. Hippocampal orexin receptors inactivation reduces PTZ induced seizures of male rats (2015) Pharmacology Biochemistry and Behavior, 130, pp. 77-83.

DOI: 10.1016/j.pbb.2015.01.006

Introduction Orexin has been shown to be involved in a number of physiological and behavioral processes including, feeding and metabolism, reward, nociception, and anxiety. Furthermore, orexin can cause increased neuronal excitability that gives rise to epileptic activity. The distribution of orexin receptor expression in the hippocampus, suggests a possible importance of orexin in the control of seizures in the temporal lobe epilepsy. Therefore, in this study, the effect of hippocampal orexin 1 and 2 receptors on seizure and glutamate and GABA (gamma-aminobutyric acid) contents was explored. Materials and methods Orexin 1 receptor (OX1R) antagonist (SB) and OX2R antagonist (TCS) were administrated bilaterally through separate cannulae into both hippocampi. Behavioral convulsions were provoked by intravenous pentylenetetrazol (PTZ) application model. The amount of total hippocampal glutamate and GABA contents was then measured by a biochemical method. Results SB (50 nmol) infusion reduced seizure stage, duration and decreased glutamate while GABA content was increased. SB (200 nmol) also reduced seizure stage, duration and glutamate content, without change of GABA content. TCS (20 nmol) infusion reduced seizure stage and duration without concomitant change in glutamate and GABA contents. Further, TCS (40 nmol) did neither affect the seizure nor the GABA, while decreased glutamate content. Co-administration of SB (50 nmol) with TCS (40 nmol) and also SB (200 nmol) with TCS (40 nmol) reduced seizure stage, duration and glutamate, but increased GABA content. Conclusion It is concluded that OX1R and OX2R antagonists reduce convulsive intensity, partially through alterations of hippocampal glutamate and GABA contents. © 2015 Elsevier Inc. All rights reserved.

AUTHOR KEYWORDS: GABA; Glutamate; Orexin receptor antagonist; Pentylenetetrazol; Seizures
INDEX KEYWORDS: 1 (2 methyl 6 benzoxazolyl) 3 (1,5 naphthyridin 4 yl)urea; 4 aminobutyric acid; agents interacting with transmitter, hormone or drug receptors; glutamic acid; orexin 1 receptor; orexin 2 receptor; orexin 2 receptor antagonist; unclassified drug; 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; 1-(3,4-dihydro-6,7-dimethoxy-2(1H)-isoquinolinyl)-3,3-dimethyl-2-((4-pyridinylmethyl)amino)-1-butanone; 4 aminobutyric acid; benzoxazole derivative; convulsant agent; glutamic acid; isoquinoline derivative; orexin receptor; orexin receptor antagonist; pentetrazole; pyridine derivative; urea, animal experiment; animal model; Article; behavior assessment; clinical effectiveness; clinical evaluation; comparative study; controlled study; convulsion; disease duration; dose response; hippocampus; male; neuromodulation; neurotransmission; nonhuman; pentylenetetrazole-induced seizure; priority journal; protein determination; protein expression; rat; treatment duration; analogs and derivatives; animal; antagonists and inhibitors; chemically induced; drug effects; hippocampus; metabolism; microinjection; seizure, Rattus, Animals; Benzoxazoles; Convulsants; gamma-Aminobutyric Acid; Glutamic Acid; Hippocampus; Isoquinolines; Male; Microinjections; Orexin Receptor Antagonists; Orexin Receptors; Pentylenetetrazole; Pyridines; Rats; Seizures; Urea

Alijan-Pour, J., Abrari, K., Lashkar Bluki, T., Ghorbanian, M.T., Goudarzi, I., Elahdadi Salmani, M., Mirshekar, M. Erratum: Acute ethanol administration affects memory reactivation: A look at the neuronal density and apoptosis in the rat hippocampus (Pharmacology Biochemistry and Behavior (2012) 102:2 (321 - 328)) (2014) Pharmacology Biochemistry and Behavior, 125, p. 85.

DOI: 10.1016/j.pbb.2014.05.020
INDEX KEYWORDS: Erratum; retracted article
PUBLISHER: Elsevier Inc.

Said Mohammadi, H., Goudarzi, I., Lashkarbolouki, T., Abrari, K., Elahdadi Salmani, M. Chronic administration of quercetin prevent spatial learning and memory deficits provoked by chronic stress in rats (2014) Behavioural Brain Research, 270, pp. 196-205.

DOI: 10.1016/j.bbr.2014.05.015

There are several reports that cognitive impairment is observed in stress related disorders and chronic stress impairs learning and memory. However, very few studies have looked into the possible ways of preventing this stress-induced deficit. This research study was conducted to evaluate the effects of quercetin, a natural flavonoid, with strong antioxidant and free radical scavenger properties, on chronic stress induced learning and memory deficits and oxidative stress in hippocampus. For chronic stress, rats were restrained daily for 6. h/day (from 9:00 to 15:00) for 21 days in well-ventilated plexiglass tubes without access to food and water. The animals were injected with quercetin or vehicle 60. min before restraint stress over a period of 21 days. Then, rats trained with six trials per day for 6 consecutive days in the water maze. On day 28, a probe test was done to measure memory retention. In addition, oxidative stress markers in the hippocampus were evaluated. Results of this study demonstrated that chronic stress exposure rats exhibited higher escape latency during training trials and reduced time spent in target quadrant, higher escape location latency and average proximity in probe trial test. Quercetin (50. mg/kg) treatment during restraint stress (21 days) markedly decreased escape latency and increased time spent in target quadrant during Morris water maze task. In comparison to vehicle treated group, chronic-stress group had significantly higher malondialdehyde (MDA) levels, significantly higher superoxide dismutase (SOD) activity and significantly lower glutathione peroxidase (GPx) activity in the hippocampus. Quercetin treatment caused a significant decrease in the hippocampus MDA levels and improves SOD and GPx activities in stressed animals. Finally, quercetin significantly decreased plasma corticosterone levels in stressed animals. Based on results of this study, chronic stress has detrimental effects on learning and memory and quercetin treatment can prevent from oxidative stress and impairment of learning and memory induced by chronic stress. © 2014 Elsevier B.V.

AUTHOR KEYWORDS: Chronic stress; Oxidative stress; Quercetin; Rat; Spatial memory
INDEX KEYWORDS: corticosterone; glutathione peroxidase; malonaldehyde; quercetin; superoxide dismutase; antioxidant; corticosterone; glutathione peroxidase; malonaldehyde; quercetin; superoxide dismutase, amnesia; analysis of variance; animal experiment; animal model; antioxidant activity; article; chronic stress; cognition; controlled study; corticosterone blood level; diet therapy; enzyme activity; hippocampus; immobilization stress; latent period; memory consolidation; Morris water maze test; neuroprotection; nonhuman; oxidative stress; priority journal; probe test; rat; spatial learning; training; animal; blood; complication; drug effects; exercise; male; maze test; Memory Disorders; mental stress; metabolism; neuropsychological test; procedures; psychology; spatial learning; spatial memory; time; treatment outcome; Wistar rat, Animals; Antioxidants; Corticosterone; Glutathione Peroxidase; Hippocampus; Male; Malondialdehyde; Maze Learning; Memory Disorders; Neuropsychological Tests; Quercetin; Rats; Rats, Wistar; Restraint, Physical; Spatial Learning; Spatial Memory; Stress, Psychological; Superoxide Dismutase; Time Factors; Treatment Outcome

Hatami, S., Zavareh, S., Salehnia, M., Lashkarbolouki, T., Ghorbanian, M.T., Karimi, I. Total oxidative status of mouse vitrified pre-antral follicles with pre-treatment of alpha lipoic acid (2014) Iranian biomedical journal, 18 (3), pp. 181-188.

BACKGROUND: Cryopreservation of pre-antral follicles is a hopeful technique to preserve female fertility. The aim of the present study was to evaluate reactive oxygen species (ROS) and total antioxidant capacity (TAC) levels of mouse vitrified pre-antral follicles in the presence of alpha lipoic acid (ALA).
METHODS: Isolated pre-antral follicles (140-150 µm in diameter) were divided into vitrified-warmed and fresh groups. Each group was subjected to in vitro maturation with or without ALA for 12 days, followed by adding human chronic gonadotropin to induce ovulation. In vitro fertilization was performed to evaluate their developmental competence. In parallel, the amount of ROS and TAC were assessed after 0, 24, 48, 72, and 96 h of culture by 2',7'-dichlorofluorescin assay and ferric reducing/antioxidant power assay, respectively.
RESULTS: The respective rates of survival, antrum formation, and metaphase II oocytes were significantly higher in ALA-supplemented groups compared to the groups not treated with ALA. TAC and ROS levels were significantly decreased and increased, respectively during the culture period up to 96 h in the absence of ALA in both vitrified and non-vitrified samples. However, with pretreatment of ALA, TAC levels were increased significantly and remained constant up to 96 h in vitrified-warmed pre-antral follicles, while ROS levels completely returned to the level of starting point after 96 h of culture in the presence of ALA.
CONCLUSION: Pretreatment of ALA positively influences development of pre-antral follicles in vitrified and non-vitrified samples through increasing follicular TAC level and decreasing ROS levels.

INDEX KEYWORDS: antioxidant; reactive oxygen metabolite; thioctic acid, animal; cell culture; cell differentiation; drug effects; female; human; metabolism; mouse; oocyte; ovary follicle; oxidation reduction reaction; vitrification, Animals; Antioxidants; Cell Differentiation; Cells, Cultured; Female; Humans; Mice; Oocytes; Ovarian Follicle; Oxidation-Reduction; Reactive Oxygen Species; Thioctic Acid; Vitrification

Firozan, B., Goudarzi, I., Elahdadi Salmani, M., Lashkarbolouki, T., Rezaei, A., Abrari, K. Estradiol increases expression of the brain-derived neurotrophic factor after acute administration of ethanol in the neonatal rat cerebellum (2014) European Journal of Pharmacology, 732 (1), pp. 1-11.

DOI: 10.1016/j.ejphar.2014.02.041

Recently it has been shown that estradiol prevents the toxicity of ethanol in developing cerebellum. The neuroprotective effect of estradiol is not due to a single phenomenon but rather encompasses a spectrum of independent proccesses. According to the specific timing of Purkinje cell vulnerability to ethanol and several protective mechanisms of estradiol, we considered the neurotrophin system, as a regulator of differentiation, maturation and survival of neurons during CNS development. Interactions between estrogen and Brain derived neurotrophic factor (BDNF, an essential factor in neuronal survival) lead us to investigate involvement of BDNF pathway in neuroprotective effects of estrogen against ethanol toxicity. In this study, 17β-estradiol (300-900 μg/kg) was injected subcutaneously in postnatal day (PD) 4, 30 min prior to intraperitoneal injection of ethanol (6 g/kg) in rat pups. Eight hours after injection of ethanol, BDNF mRNA and protein levels were assayed. Behavioral studies, including rotarod and locomotor activity tests were performed in PD 21-23 and histological study was performed after completion of behavioral tests in PD 23. Our results indicated that estradiol increased BDNF mRNA and protein levels in the presence of ethanol. We also observed that pretreatment with estradiol significantly attenuated ethanol-induced motoric impairment. Histological analysis also demonstrated that estradiol prevented Purkinje cell loss following ethanol treatment. These results provide evidence on the possible mechanisms of estradiol neuroprotection against ethanol toxicity. © 2014 Elsevier B.V.

AUTHOR KEYWORDS: 17β-estradiol; Brain derived neurotrophic factor; Ethanol; Neuroprotection; Purkinje cell
INDEX KEYWORDS: alcohol; brain derived neurotrophic factor; complementary DNA; estradiol; messenger RNA; alcohol; brain derived neurotrophic factor; central depressant agent; estradiol; neuroprotective agent, alcohol blood level; animal behavior; animal tissue; article; cell loss; cerebellum; controlled study; DNA synthesis; drug mechanism; enzyme linked immunosorbent assay; experimental locomotor activity test; female; histology; male; motor dysfunction; neuroprotection; newborn; nonhuman; open field test; perinatal period; priority journal; protein expression; Purkinje cell; rat; reverse transcription polymerase chain reaction; RNA extraction; rotarod test; animal; blood; cerebellum; drug effects; metabolism; motor activity; pathology; psychomotor performance; signal transduction, Animals; Animals, Newborn; Brain-Derived Neurotrophic Factor; Central Nervous System Depressants; Cerebellum; Estradiol; Ethanol; Motor Activity; Neuroprotective Agents; Psychomotor Performance; Rats; Signal Transduction

Mirzaeiyan, L., Ghorbanian, M.-T., Lashkarbolouki, T., Haji-Ghasem-Kashani, M., Dehghan, R. Examination of antioxidant enzymes andmatrix metalloproteinases in conditional medium of bone marrow mesenchymal stem cells and adipose-derived stem cells in vitro (2014) Koomesh, 15 (3), pp. 350-358.

Introduction: Mesenchymal stem sells (MSCs) have an important role in cell therapy due to those high proliferation, differentiation and cell regeneration capacity. Advent signs of Replicative Cellular Senescence (R.C.S) in culture condition are one of the problems in stem cells culture pathway before treatment. R.C.S is associated with reducing the capacity of antioxidant enzymes and matrix metalloproteinase (MMPs) proteins changes. The aim of this study was to areinvestigate and compare the production capacity of antioxidant superoxiddismutase (SOD) and glutathione peroxidase (GPx) enzymes and matrix metalloproteinases (MMP-2) in conditional medium of rat bone marrow mesenchymal stem cells (BMSCs) and adipose-derived stem cells (ADSCs). Materials and Methods: BMSCs and ADSCs were respectively isolated from the tibia and femur bones and subcutaneous adipose tissues. These cells were cultured for alternative 7 passages in α-MEM supplemented with 10% fetal bovine serum. Evaluation of antioxidant and MMP activity in the conditional medium without serum was respectively assayed by enzymatic assay and zymography. Results: Two types of cells studied almost identical have most activity in the expression of SOD and GPx, respectively, in 5 and 4-6 passages. Also, demonstrated MMP activity is highest in the fourth passage. On the other hand, in these cells, membrane health reported with measurement of MDA and LDH. Conclusion: Adipose tissue has a population of stem cells with high capacity of antioxidant. Also, BMSCs and ADSCs are at highest level of antioxidant and MMP expression capacity in 4-6 passages.

AUTHOR KEYWORDS: Antioxidant enzymes; Matrix metalloproteinases; Mesenchymal stem cells; Replicative Cellular Senescence
INDEX KEYWORDS: glutathione peroxidase; matrix metalloproteinase; superoxide dismutase; antioxidant; glutathione peroxidase; superoxide dismutase, adipose derived stem cell; animal cell; antioxidant activity; article; cell culture; cell therapy; controlled study; enzymatic assay; hematopoietic stem cell; mesenchymal stem cell; nonhuman; protein expression; rat; replicative cellular senescence; zymography; hematopoietic stem cell

Hatami, S., Zavareh, S., Salehnia, M., Lashkarbolouki, T., Karimi, I. Comparison of oxidative status of mouse pre-antral follicles derived from vitrified whole ovarian tissue and vitrified pre-antral follicles in the presence of alpha lipoic acid (2014) Journal of Obstetrics and Gynaecology Research, 40 (6), pp. 1680-1688.

DOI: 10.1111/jog.12394

Aim The main goal of this study was to compare developmental competence and oxidative status of vitrified-warmed pre-antral follicles (VPF) with pre-antral follicles derived from vitrified-warmed ovarian tissue (VOF) in the presence of alpha lipoic acid (ALA). Materials and Methods Ovarian tissue and isolated pre-antral follicles were exposed to equilibration solution and then vitrification solution. After thawing of LN2 snap-frozen samples, pre-antral follicles were cultured with or without ALA for 12 days that followed by hCG-induced ovulation. MII oocytes were in vitro fertilized and embryo cleavage assessed. Reactive oxygen species (ROS) and total antioxidant capacity (TAC) levels of cultured pre-antral follicles were measured. Results The rates of survival, antral-like cavity formation, MII oocytes, fertilization, 2-cell embryo and blastocyst development were higher in VPF compared to VOF. These rates were higher in ALA-supplemented groups in comparison to their respective groups. An increase and a decrease in ROS production and TAC levels were observed up to the 96 h during cultivation period, respectively. ROS level was lower in cultured VPF compared to VOF. In ALA-treated groups, ROS level decreased to reach comparable values of starting point and TAC levels increased after 24 h of culture and then remained constant. Conclusion Developmental outcomes showed vitrification of pre-antral follicles is more appropriate method than that of whole ovarian tissue. Moreover, it seems that inclusion of ALA improved in vitro development of pre-antral follicles in both vitrified and non-vitrified samples. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

AUTHOR KEYWORDS: alpha lipoic acid; ovarian tissue; oxidative status; vitrification
INDEX KEYWORDS: reactive oxygen metabolite; thioctic acid; antioxidant; reactive oxygen metabolite; thioctic acid, animal cell; article; blastocyst; cell survival; comparative study; controlled study; embryo; embryo cleavage; embryo development; female; fertilization in vitro; mouse; nonhuman; oocyte; ovary follicle; oxidative stress; thawing; vitrification; vitrified warmed ovarian tissue; vitrified warmed preantral follicle; animal; cryopreservation; drug effects; fertilization; metabolism; ovary follicle, Animals; Antioxidants; Cryopreservation; Embryonic Development; Female; Fertilization; Mice; Ovarian Follicle; Reactive Oxygen Species; Thioctic Acid; Vitrification

Hatami, S., Zavareh, S., Salehnia, M., Lashkarbolouki, T., Ghorbanian, M.T., Karimi, I. Total oxidative status of mouse vitrified pre-antral follicles with pre-treatment of alpha lipoic acid (2014) Iranian Biomedical Journal, 18 (3), pp. 180-187.

DOI: 10.6091/ibj.1258.2014

Background: Cryopreservation of pre-antral follicles is a hopeful technique to preserve female fertility. The aim of the present study was to evaluate reactive oxygen species (ROS) and total antioxidant capacity (TAC) levels of mouse vitrified pre-antral follicles in the presence of alpha lipoic acid (ALA). Methods: Isolated pre-antral follicles (140-150 μm in diameter) were divided into vitrified-warmed and fresh groups. Each group was subjected to in vitro maturation with or without ALA for 12 days, followed by adding human chronic gonadotropin to induce ovulation. In vitro fertilization was performed to evaluate their developmental competence. In parallel, the amount of ROS and TAC were assessed after 0, 24, 48, 72, and 96 h of culture by 2',7'-dichlorofluorescin assay and ferric reducing/antioxidant power assay, respectively. Results: The respective rates of survival, antrum formation, and metaphase II oocytes were significantly higher in ALA-supplemented groups compared to the groups not treated with ALA. TAC and ROS levels were significantly decreased and increased, respectively during the culture period up to 96 h in the absence of ALA in both vitrified and non-vitrified samples. However, with pretreatment of ALA, TAC levels were increased significantly and remained constant up to 96 h in vitrified-warmed pre-antral follicles, while ROS levels completely returned to the level of starting point after 96 h of culture in the presence of ALA. Conclusion: Pretreatment of ALA positively influences development of pre-antral follicles in vitrified and nonvitrified samples through increasing follicular TAC level and decreasing ROS levels.

AUTHOR KEYWORDS: Alpha lipoic acid (ALA); Pre-antral follicle; Reactive oxygen species (ROS); Total antioxidant capacity (TAC); Vitrification
INDEX KEYWORDS: chorionic gonadotropin; dichlorodihydrofluorescein diacetate; reactive oxygen metabolite; thioctic acid, animal cell; antioxidant activity; antioxidant assay; article; blastocyte; cell culture; cell isolation; cell maturation; cell structure; cell survival; controlled study; enzyme assay; female; fertilization in vitro; in vitro study; metaphase; nonhuman; oocyte development; ovary follicle cell; ovulation; ovulation induction; oxidation; rat; vitrification

Hatami, S., Zavareh, S., Salehnia, M., Lashkarbolouki, T., Ghorbanian, M.T., Karimi, I. The impact of alpha lipoic acid on developmental competence of mouse vitrified pre-antral follicles in comparison to those isolated from vitrified ovaries (2014) Iranian Journal of Reproductive Medicine, 12 (1), pp. 57-64.

Background: Cryopreservation of ovarian tissues and pre-antral follicles is a promising prospect for preservation of women fertility. Objective: The aim of this study was to evaluate the in vitro developmental competence of mouse vitrified pre-antral follicles in comparison to isolated pre-antral follicles derived from vitrified ovaries in the presence of alpha lipoic acid (ALA). Materials and Methods: Pre-antral follicles derived from fresh, vitrified-warmed ovarian tissues and vitrified–warmed pre-antral follicles were cultured individually with or without ALA, followed by adding hCG to induce ovulation. The follicle growth, oocyte maturation, and embryo development were assessed. Results: The diameter and development of follicles, oocyte maturation and embryo development rates were significantly higher in ALA supplemented groups compared to the respective ALA-free conditions groups. Aforementioned parameters were significantly higher in vitrified-warmed follicles in comparison to follicles derived from vitrified-warmed ovaries. Conclusion: These findings support a superior performance of pre-antral follicles when vitrified rather than when isolated from vitrified ovaries with regard to increasing the rates of developmental parameters. Moreover, ALA improves the in vitro maturation of pre-antral follicles in vitrified and non-vitrified samples. © 2014, Research and Clinical Center for Infertitlity. All rights reserved.

AUTHOR KEYWORDS: Alpha lipoic acid; Ovary; Preantral follicles; Vitrification
INDEX KEYWORDS: chorionic gonadotropin; thioctic acid, animal cell; animal tissue; Article; controlled study; embryo; embryo development; female; fertilization in vitro; in vitro study; intermethod comparison; male; mouse; nonhuman; oocyte maturation; ovary follicle; ovary follicle development; ovulation; preantral follicle; tissue culture; vitrification

Moradi, S., Ajloo, D., Lashkarbolouki, T., Alizadeh, R., Saboury, A.A. Physicochemical studies on the interaction of gold(III) trichlorophenanthridine complex with calf thymus DNA (2013) Monatshefte fur Chemie, 144 (10), pp. 1499-1505.

DOI: 10.1007/s00706-013-1032-5

The interaction of gold(III) trichlorophenanthridine complex, [Au(phend)Cl3], with calf thymus DNA was investigated by UV-Vis absorption, circular dichroism, and fluorescence spectrophotometery as well as viscometry, cyclic voltammetry (CV), and molecular docking. The values of binding constants K b (obtained by UV-Vis) and K f (obtained by fluorescence) are 3 × 104 and 7.68 × 10 5 M-1, respectively. Evidence for intercalation comprised a hyperchromic effect at 210 nm and a hypochromic effect at 250 nm caused by the ligand, increasing the T m of DNA, increasing of viscosity, increasing the intensity of the positive peak, decreasing the intensity of the negative peak, and the positive shift of the cathodic peak potential in CV. Graphical abstract: [Figure not available: see fulltext.] © 2013 Springer-Verlag Wien.

AUTHOR KEYWORDS: DNA; Fluorescence spectroscopy; Gold complex; Intercalation compounds; Ligand docking

Moradi, F., Kashani, M.H.G., Ghorbanian, M.T., Lashkarbolouki, T. Spontaneous expression of neurotrophic factors and TH, Nurr1, nestin genes in long-term culture of bone marrow mesenchymal stem cells (2012) Cell Journal, 13 (4), pp. 243-250.

Objective: It has been reported that rat bone marrow stromal cells (BMSCs) can be spontaneously differentiated into neural-like cells without any supplemental growth factors and/or chemical treatment after long-term culture.This study aims to determineWhether, growth factors secreted by MSCs could induce self-differentiation into neural-like cells in a long-term culture. Materials and Methods: This study consisted of two groups: i. rat BMSCs (passage 5) were cultured in alfa- minimal essential medium (α-MEM) and 10% fetal bovine serum (FBS) without the addition of inducer and exchanging medium for three weeks, as the experimental group and ii.rat BMSCs (passage 5) as the control group. Each group was analysed by reverse transcriptase polymerase chain reaction (RT-PCR) to evaluate the expressions of neurotrophic factors and neural marker genes. Statistical analyses were carried out using one-way analysis of variance (ANOVA) and Tukey's multiple comparison with SPSS software (version 16). P< 0.05 was considered statistically significant. Results: The experimental group (fifth passage of BMSCs) obtained from adult rats spontaneously differentiated into neural precursor cells after long-term culture. Cultured cells expressed tyrosine hydroxylase (TH), Nurr1 and nestin genes. Furthermore, some growing cells in suspension became neurosphere-like. Self-differentiated rat MSCs (SDrMSCs) expressed significantly higher levels of NGF (0.96 ± 0.16), nestin (0.63 ± 0.08), and Nurr1 (0.80 ± 0.10) genes (p<0.05). Conclusion: In this study, we reported that rMSCs in long-term culture underwent spontaneous transformation to neural precursors without the supplement of growth factors and specific chemicals. Cells expressed neural markers such as: TH, Nurr1, and nestin genes. [/accordion]
AUTHOR KEYWORDS: Bone marrow; Long-term culture; Mesenchymal stem cells; Neurotrophic factors; Spontaneous differentiation
INDEX KEYWORDS: cell nucleus receptor; nestin; neurotrophic factor; tyrosine 3 monooxygenase, analysis of variance; animal cell; article; cell culture; controlled study; hematopoietic stem cell; marker gene; mesenchymal stem cell; nonhuman; protein expression; rat; reverse transcription polymerase chain reaction; statistical analysis; stem cell

Alijan-pour, J., Abrari, K., Bluki, T.L., Ghorbanian, M.T., Goudarzi, I., Salmani, M.E. Ethanol disrupts reactivated contextual conditioned fear memory: Behavioral and histological perspectives (2012) Cell Journal, 13 (4), pp. 265-274.

Objective: This research study is an attempt to examine whether the administration of ethanol after memory reactivation would modulate subsequent expression of memory in rats. Additionally, we examined whether this administration alters the density of Cornu Ammonis (CA)1 and CA3 pyramidal and dentate gyrus (DG) granule cells. Materials and Methods: In this experimental study, adult male Wistar rats (200-300 g) were trained in a fear conditioning system using two 1 second, 0.6 mA shocks with an interval of 180 seconds. Twenty four hours later rats were returned to the chamber for 120 seconds. Immediately after reactivation they were injected with ethanol (0.5, 1, 1.5 mg/kg) or saline. 1, 7 and 14 days after reactivation, rats were returned to the context for 5 minutes. Seconds of freezing (absence of all movement except respiration) were scored. In the second experiment (described in the previous paragraph), after test 1, animals were anesthetized with sodium pentobarbital and perfused transcardially with phosphate buffer (10 minutes) and 4% paraformaldehyde (15 minutes). The brains were postfixed in phosphate-buffered 4% paraformaldehyde (24 hours) and 30% sucrose. 10-μm sections were stained with cresyl violet. Data were analyzed by 1-and 2-way ANOVA for repeated measurements by means of SPSS 16.0. Tukey's post hoc test was performed to determine the source of detected significant differences. P <0.05 were considered significant. Data are presented as mean ± SEM. Results: Findings from the first experiment indicated that ethanol at a dose of 1.5 mg/kg significantly impaired recall of memory only in the first test. The density of CA1 and CA3 pyramidal and DG granule cells in the ethanol group was decreased (p< 0.01) compared with control group respectively 43.7%, 35.8%, and 37.8. Conclusion: The data demonstrate that ethanol exposure impairs post retrieval processes. Moreover, ethanol decreases the density of CA1, CA3 and DG cells. Presumably it would be a correlation between our behavioral and histological results. [/accordion]
AUTHOR KEYWORDS: Conditioning; Ethanol; Hippocampus; Reconsolidation
INDEX KEYWORDS: alcohol; paraformaldehyde; pentobarbital; phosphate buffered saline, analysis of variance; animal cell; animal experiment; animal model; animal tissue; article; behavior; clinical examination; conditioning; controlled study; dentate gyrus; experimental study; fear; granule cell; hippocampal CA1 region; hippocampal CA3 region; histology; male; medical research; memory; nonhuman; perfusion; rat

Rahimi Shourmasti, F., Goudarzi, I., Lashkarbolouki, T., Abrari, K., Elahdadi Salmani, M., Goudarzi, A. Effects of riluzole on harmaline induced tremor and ataxia in rats: Biochemical, histological and behavioral studies (2012) European Journal of Pharmacology, 695 (1-3), pp. 40-47.

DOI: 10.1016/j.ejphar.2012.08.014

Essential tremor (ET) is one of the most common and most disabling movement disorders among adults. The drug treatment of essential tremor remains unsatisfactory. Additional therapies are required for patients with inadequate response or intolerable side effects. Thus, we aimed to investigate the therapeutic effects of riluzole on harmaline-induced tremor and ataxia in rat, and determining whether riluzole exerts its effect through modulation of glutamate levels in cerebellum. The study included 5 groups of Wistar rats weighing 80-100 g, injected with harmaline (50 mg/kg i.p.) for inducing experimental tremors and ataxia. The rats in group 1 served as control (saline induced) and group 2 received harmaline alone, whereas the animals in groups 3, 4 and 5, were also given riluzole intraperitoneally at doses of 2, 4 and 8 mg/kg 10 min after harmaline administration, respectively. The intensity and duration of tremor were recorded. Rotarod test, distance traveled and number of crossings were used to evaluate motor performance. Results of this study demonstrated that riluzole dose dependently attenuated duration and intensity of harmaline-induced tremors. Also, riluzole significantly improves time to fall, distance traveled and number of crossings in combined riluzole and harmaline treated rats. Histological analysis indicated that harmaline could cause vermis Purkinje cell (PC) loss and riluzole prevented this toxic effect. Harmaline also could increase glutamate levels in vermis and treatment with riluzole restored glutamate levels. In conclusion, riluzole has relatively protective effects on harmaline-induced tremor, probably related to its inhibitory effect on glutamatergic neurotransmission. © 2012 Elsevier B.V. All rights reserved.

AUTHOR KEYWORDS: (Rat); Cerebellum; Harmaline; Riluzole; Tremor
INDEX KEYWORDS: riluzole, animal behavior; animal experiment; animal model; animal tissue; article; ataxia; cerebellum; controlled study; dose response; drug dose comparison; drug effect; histopathology; motor performance; neuromodulation; neuroprotection; neurotransmission; nonhuman; open field test; priority journal; Purkinje cell; rat; rotarod test; tremor, Animals; Ataxia; Behavior, Animal; Cerebellum; Glutamates; Harmaline; Ion Channels; Male; Neuroprotective Agents; Rats; Rats, Wistar; Riluzole; Rotarod Performance Test; Time Factors; Tremor

Ramezani, A., Goudarzi, I., Lashkarbolouki, T., Ghorbanian, M.T., Elahdadi Salmani, M., Abrari, K. Neuroprotective effects of the 17β-estradiol against ethanol-induced neurotoxicity and oxidative stress in the developing male rat cerebellum: Biochemical, histological and behavioral changes (2011) Pharmacology Biochemistry and Behavior, 100 (1), pp. 144-151.

DOI: 10.1016/j.pbb.2011.07.010

During particular periods of central nervous system (CNS) development, exposure to ethanol can decrease regional brain growth and can result in selective loss of neurons. Unfortunately, there are few effective means of attenuating damage in the immature brain. In this study, the possible antioxidant and neuroprotective properties of 17β-estradiol against ethanol-induced neurotoxicity was investigated. 17β-estradiol (600 μg/kg) was injected subcutaneously in postnatal day (PD) 4 and 5, 30 min prior to intraperitoneal injection of ethanol (6 g/kg) in rat pups. Ninety minutes after injection of ethanol, the activities of several antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (Gpx) in vermis of cerebellum were assayed. Thiobarbituric acid reactive substance (TBARS) levels were also measured as a marker of lipid peroxidation. Behavioral studies, including rotarod and locomotor activity tests were performed in PD 21-23 and histological study was performed after completion of behavioral measurements in postnatal day 23. The results of the present work demonstrated that ethanol could induce lipid peroxidation, increase TBARS levels and decrease glutathione peroxidase levels in pup cerebellum. We also observed that ethanol impaired performance on the rotarod and locomotor activities of rat pups. However, treatment with 17β-estradiol significantly attenuated motoric impairment, the lipid peroxidation process and restored the levels of antioxidants. Histological analysis also indicated that ethanol could decrease vermis Purkinje cell count and 17β-estradiol prevented this toxic effect. These results suggest that ethanol may induce lipid peroxidation in the rat pups cerebellum while treatment with 17β-estradiol improves motor deficits by protecting the cerebellum against ethanol toxicity. © 2011 Elsevier Inc.

AUTHOR KEYWORDS: 17β-estradiol; Ethanol; Lipid peroxidation; Oxidative stress; Purkinje cell; Rat pups
INDEX KEYWORDS: alcohol; catalase; estradiol; glutathione peroxidase; superoxide dismutase; thiobarbituric acid reactive substance, animal experiment; antioxidant activity; article; behavior change; biochemistry; brain development; cerebellum; cerebellum vermis; controlled study; female; histology; locomotion; male; neuroprotection; neurotoxicity; nonhuman; oxidative stress; perinatal period; priority journal; Purkinje cell; rat; rotarod test; task performance, Animals; Animals, Newborn; Cerebellum; Estradiol; Ethanol; Male; Motor Activity; Motor Skills Disorders; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Wistar, Rattus

Tavakoli, Z., Ardestani, S.K., Lashkarbolouki, T., Kariminia, A., Salehi, T.Z., Tavassoli, N. DNAs from Brucella strains activate efficiently murine immune system with production of cytokines, reactive oxygen and nitrogen species (2009) Iranian Journal of Allergy, Asthma and Immunology, 8 (3), pp. 127-134.

Brucellosis is an infectious disease with high impact on innate immune responses which is induced partly by its DNA. In the present study the potential differences of wild type and patients isolates versus attenuated vaccine strains in terms of cytokines, ROS and NO induction on murine splenocytes and peritoneal macrophages were investigated. This panel varied in base composition and included DNA from B. abortus, B. melitensis, B.abortus strain S19 and melitensis strain Rev1, as attenuated live vaccine. Also we included Escherichia coli DNA, calf thymus DNA (a mammalian DNA), as controls. These DNA were evaluated for their ability to stimulate IL-12, TNF-α, IL-10, IFN-γ and ROS production from spleenocytes as well as NO production from peritoneal macrophages. Spleen cells were cultured in 24 well at a concentration of 106 cells/ ml with subsequent addition of 10 μg/ml of Brucella or Ecoli DNAs. These cultures were incubated at 37°C with 5% CO2 for 5 days. Supernatants were harvested and cytokines, ROS and NOx were evaluated. It was observed that TNF-α was induced in days 1,3,5 by all Brucella strains DNAs and E. coli DNA, IL-10 only was induced in day 1, IFN-γ was induced only in day 5 and IL-12 not induced. ROS and NOx were produced by all strains; however, we observed higher production of NOx which were stimulated by DNA of B. melitensis. Copyright© 2009, Iranian Journal of Allergy, Asthma and Immunology. All rights reserved.

AUTHOR KEYWORDS: Cytokines; Genomic DNAs from brucella strains; Nitrogen species; Reactive oxygen
INDEX KEYWORDS: bacterial DNA; cytokine; gamma interferon; interleukin 10; interleukin 12; live vaccine; nitrate; nitrite; nitrogen oxide; reactive nitrogen species; reactive oxygen metabolite; tumor necrosis factor alpha, animal cell; animal experiment; animal tissue; article; bacterial strain; bacterium isolate; Brucella; Brucella abortus; Brucella melitensis; calf (bovine); cell culture; controlled study; cytokine production; cytokine release; DNA base composition; Escherichia coli; female; immune response; immunomodulation; mouse; nonhuman; peritoneum macrophage; spleen cell; thymus; wild type, Animals; Brucella; Cells, Cultured; Cytokines; DNA, Bacterial; Escherichia coli; Interferon-gamma; Interleukin-10; Mice; Mice, Inbred BALB C; Nitric Oxide; Oligodeoxyribonucleotides; Reactive Nitrogen Species; Reactive Oxygen Species; Tumor Necrosis Factor-alpha

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