Publications by authors named "Naser Mirazi"

23 Publications

  • Page 1 of 1

Protective effects of the fruit extract of raspberry ( L.) on pituitary-gonadal axis and testicular histopathology in streptozotocin induced diabetic male rats.

Avicenna J Phytomed 2021 Mar-Apr;11(2):199-209

Department of Clinical Biochemistry, School of Medicine, Hamedan University of Medical Sciences, Hamedan, Iran.

Objective: Protective effects of raspberry ( L.) fruit extract on pituitary-gonadal axis and testicular tissue in diabetic male rats, were investigated.

Materials And Methods: Sixty male rats were divided into control, sham (saline treated), streptozotocin (STZ)-diabetic, and STZ-diabetic animals treated with 50, 100 and 200 mg/kg/day of raspberry extract. After 4 weeks, blood samples were obtained and left testes were removed and prepared for histopathological studies. Serum levels of Luteinizing hormone (LH), Follicle stimulating hormone (FSH), testosterone, Nitric oxide (NO), and malondialdehyde (MDA), as well as superoxide dismutase (SOD) and catalase (CAT) activity level were assayed. Sperm number and motility in the epididymis samples were measured. Data were analyzed using ANOVA (one-way analysis of variance).

Results: Serum levels of LH, FSH and MDA significantly increased in diabetic rats, however, treatment with the extract significantly reversed the alterations. Serum levels of testosterone and NO, activity of SOD and CAT, and sperm number and motility significantly decreased and severe destruction of testicular histology was observed in diabetic animals while treatment with the extract significantly reversed the pathologic alterations observed in diabetic rats. According to the results, 100 and 200 mg/kg of the extract were able to effectively reverse the diabetes complications.

Conclusion: Our findings demonstrated that the fruit extract of raspberry has protective effects on male reproductive system in diabetic rats partially due to its improving effects on NO system, and SOD and CAT activity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051313PMC
April 2021

Effects of vanillic acid on Aβ-induced oxidative stress and learning and memory deficit in male rats.

Brain Res Bull 2021 May 27;170:264-273. Epub 2021 Feb 27.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran; Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address:

Alzheimer's disease (AD) is a neurodegenerative disease, in which the accumulation of β-amyloid (Aβ) peptide in the extracellular space causes a progressive reduction in cognitive performance. Aβ stimulates active oxygen species generation leading to oxidative stress and neural cell death. Vanillic Acid (VA) is the oxidant form of vanillin widely found in vanilla beans. VA has many properties, such as suppressing apoptosis and eliminating the harmful effects of oxidative stress in animal models. The VA effects on impaired learning and memory in Aβ rats were assessed. Forty adults male Wistar rats were assigned to the following five groups in random: the control, sham (received saline (vehicle) via intracerebroventricular (ICV) injection), Aβ (received Aβ1-40 via ICV injection), VA (50 mg/kg by oral gavage once a day through four weeks), and Aβ + VA (50 mg/kg) groups. Open field test, novel object recognition (NOR) test, Morris water maze (MWM) test, and passive avoidance learning (PAL) task were performed, and finally, we determined the malondialdehyde (MDA), total antioxidant capacity (TAC) and total oxidant status (TOS) levels. Aβ decreased the cognitive memory in NOR, spatial memory in MWM, and passive avoidance memory in PAL tests. In contrast, VA improved learning and memory in the treated group. Aβ significantly increased MDA and TOS and decreased TAC levels, whereas VA treatment significantly reversed TAC, TOS and MDA levels. In conclusion, VA decreased the Aβ effects on learning and memory by suppressing oxidative stress and can be regarded as a neuroprotective substance in AD.
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http://dx.doi.org/10.1016/j.brainresbull.2021.02.024DOI Listing
May 2021

Vanillic acid attenuates amyloid β1-40-induced long-term potentiation deficit in male rats: an in vivo investigation.

Neurol Res 2021 Feb 24:1-8. Epub 2021 Feb 24.

Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.

: Alzheimer disease (AD) is a neurodegenerative disorderliness that involves deductible progressive cognition function caused by amyloid-beta (Aβ) peptide accumulation in the interstitial space. The increase of Aβ stimulates all kinds of active oxygen and causes oxidative stress and apoptosis. In this investigation, we researched the neuroprotective impacts of vanillic acid (VA) on the Aβ-induced (Aβ1-40) long-term potentiation (LTP) of the hippocampus - a commonly probed synaptic plasticity model that happens at the same time as memory and learning - in the AD rats.: Forty-five male Wistar rats were categorized into five groups (n = 8 rats/group, 200-220 g), and studied as control (standard diet), sham (vehicle), VA (50 mg/kg), Aβ and Aβ + VA (50 mg/kg) groups. electrophysiological recordings were implemented after the stereotaxic surgery to gauge the excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude in the dentate gyrus of the hippocampus. By the stimulation at high-frequency of the perforate pathway, long-term potentiation (LTP) was induced. To assess the plasma levels of malondialdehyde (MDA) and total thiol group (TTG), blood samples were garnered.: In the Aβ-injected rats, EPSP slope, and PS amplitude were significantly reduced after the induction of LTP. Thus, the findings demonstrate that VA decreases the impacts of Aβ on LTP; also, the treatments through VA neuroprotective against the negative effects of Aβ on the synaptic plasticity of the hippocampus can decrease the MDA levels and also increase the TTG levels significantly.: Therefore, based on this experiment on male rats, VA has neuroprotective effects and antioxidants benefits against the Aβ-mediated inhibition of long-term potentiation.
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http://dx.doi.org/10.1080/01616412.2021.1893565DOI Listing
February 2021

Attenuating properties of L. on oxidative damage and inflammatory response following streptozotocin-induced diabetes in the male Wistar rats.

J Diabetes Metab Disord 2020 Dec 3;19(2):1311-1316. Epub 2020 Oct 3.

Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.

Purpose: Diabetes mellitus is a prevalent metabolic disorder that entails numerous complications in various organs. In current era, different types of diseases are being treated by the applications of herbs. The present study is aimed at investigating the anti-inflammatory and antioxidant effects of the hydroethanolic extracts (RFHE) in the streptozotocin (STZ)-induced diabetic rats.

Methods: At this experimental research, male Wistar rats with the weight of 220 ± 20 g, were categorized randomly into five groups of vehicles as control, STZ (60 mg kg of body weight, intraperitoneally (i.p.)) and RFHE (50, 100 and 200 mg kg, i.p.). In the last stage (end of week 4) of the experiment, after being euthanized, the blood samples of the rats were collected for measuring malondialdehyde (MDA), glutathione (GSH), total antioxidant status (TAS) as well as inflammatory markers like tumor necrosis factor (TNF)-α, interleukin (IL)-6 and C-reactive protein (CRP).

Results: Data from this study was revealed that diabetes causes oxidative damage and consequently the serum level of inflammatory markers rises. RFHE was shown to be significantly correlated with lowering the level of MDA, TNF-α, IL-6 and CRP of diabetic rats. Moreover, RFHE significantly elevated the GSH and TAS serum levels in diabetic rats when compared with STZ group.

Conclusions: RFHE might have anti-diabetic properties; this outcome may be mediated by high antioxidant and anti-inflammatory effects.
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http://dx.doi.org/10.1007/s40200-020-00649-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843724PMC
December 2020

Ameliorative effects of endurance training and Matricaria chamomilla flowers hydroethanolic extract on cognitive deficit in type 2 diabetes rats.

Biomed Pharmacother 2021 Mar 1;135:111230. Epub 2021 Feb 1.

Department of Biology, Faculty of Basic Sciences, Bu- Ali Sina University, Hamedan, Iran.

Diabetes mellitus is mainly associated with degeneration of the central nervous system, which eventually leads to cognitive deficit. Although some studies suggest that exercise can improve the cognitive decline associated with diabetes, the potential effects of endurance training (ET) accompanied by Matricaria chamomilla (M.ch) flowers extract on cognitive impairment in type 2 diabetes has been poorly understood. Forty male Wistar rats were randomized into 5 equal groups of 8: healthy-sedentary (H-sed), diabetes-sedentary (D-sed), diabetes-endurance training (D-ET), diabetes-Matricaria chamomilla. (D-M.ch), and diabetes-endurance training-Matricaria chamomilla. (D-ET-M.ch). Nicotinamide (110 mg/kg, i.p.) and Streptozotocin (65 mg/kg, i.p.) were utilized to initiate type 2 diabetes. Then, ET (5 days/week) and M.ch (200 mg/kg body weight/daily) were administered for 12 weeks. After 12 weeks of the experiment, cognitive functions were assessed using the Morris Water Maze (MWM) test and a passive avoidance paradigm using a shuttle box device. Subsequently, using crystal violet staining, neuron necrosis was examined in the CA3 area of the hippocampus. Diabetic rats showed cognitive impairment following an increase in the number of necrotic cells in region CA3 of the hippocampal tissue. Also, diabetes increased serum levels of lipid peroxidation and decreased total antioxidant capacity in serum and hippocampal tissue. ET + M.ch treatment prevented the necrosis of neurons in the hippocampal tissue. Following positive changes in hippocampal tissue and serum antioxidant enzyme levels, an improvement was observed in the cognitive impairment of the diabetic rats receiving ET + M.ch. Therefore the results showed that treatment with ET + M.ch could ameliorate memory and inactive avoidance in diabetic rats. Hence, the use of ET + M.ch interventions is proposed as a new therapeutic perspective on the death of hippocampal neurons and cognitive deficit caused by diabetes.
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http://dx.doi.org/10.1016/j.biopha.2021.111230DOI Listing
March 2021

Human umbilical cord blood serum attenuates gentamicin-induced liver toxicity by restoring peripheral oxidative damage and inflammation in rats.

Basic Clin Pharmacol Toxicol 2021 Feb 13;128(2):268-274. Epub 2020 Oct 13.

Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.

Gentamicin (GM) is an aminoglycoside antibiotic that despite its antibacterial effects, its use is restricted due to numerous side effects. The umbilical cord serum contains various biomolecules that have protective impacts on the damaged tissues. The aim of this study was to gauge the protective effect of human umbilical cord blood serum (hUCBS) on GM-induced hepatotoxicity. In this experimental study, 28 male Wistar rats, weighing 220 ± 20 g, were randomly categorized into 4 groups including control, GM (100 mg/kg), hUCBS at doses of 1 and 2% along with GM (100 mg/kg) for 10 days, intraperitoneally. Twenty-four hours after the last injection, direct blood sampling was taken from the heart to obtain blood serum and liver enzymes, inflammatory cytokines and liver tissue were examined for histology. GM causes necrosis and inflammation in liver tissue. Liver enzyme and inflammatory cytokine levels were significantly increased in the GM group. Human umbilical cord blood serum significantly decreased liver enzyme and inflammatory cytokines levels in the experimental groups compared to the GM group. GM causes liver damage such as the inflammation and necrosis in liver tissue. Treating the animals with hUCBS reduced the toxic effects of GM in the liver.
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http://dx.doi.org/10.1111/bcpt.13502DOI Listing
February 2021

The effects of concurrent treatment of silymarin and lactulose on memory changes in cirrhotic male rats.

Bioimpacts 2020 24;10(3):177-186. Epub 2020 Mar 24.

Department of Pathology, Hamadan University of Medical Sciences, Hamadan, Iran.

Chronic liver disease frequently accompanied by hepatic encephalopathy (HE). Changes in the permeability of the blood-brain barrier in HE, make an easier entrance of ammonia among other substances to the brain, which leads to neurotransmitter disturbances. Lactulose (LAC), causes better defecation and makes ammonia outreach of blood. Silymarin (SM) is a known standard drug for liver illnesses. The purpose of this research was to determine the results of LAC and SM combined treatment, on the changes in memory of cirrhotic male rats. The cirrhotic model established by treatment with thioacetamide (TAA) for 18 weeks. Cirrhotic rats randomized to four groups (n = 7): TAA group (received drinking water), LAC group (2 g/kg/d LAC in drinking water), SM group (50 mg/kg/d SM by food), SM+ LAC group (similar combined doses of both compounds) for 8 weeks. The control group received drinking water. The behavior examined by wire hanging (WH), passive avoidance (PA), and open field (OF) tests. Our findings showed that treatment with SM+LAC effectively increased PA latency, compared with the control group. The results showed that the administration of LAC and SM+LAC affected the number of lines crossed, the total distance moved and velocity in the OF tests. SM and LAC have anti-inflammatory effects that are memory changing. It may be due to their useful effects. These results indicated that SM+LAC restored memory disturbance and irritated mood in the cirrhotic rats. Comparable neuroprotection was never previously informed. Such outcomes are extremely promising and indicate the further study of SM+LAC.
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http://dx.doi.org/10.34172/bi.2020.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416014PMC
March 2020

Treatment of liver and spleen illnesses by herbs: Recommendations of Avicenna's heritage "Canon of Medicine".

Avicenna J Phytomed 2019 Mar-Apr;9(2):101-116

Department of Statistics, Faculty of Basic Sciences, Bu- Ali Sina University, Hamedan, Iran.

Objective: Avicenna (Abu Ali al-Hossein ibn Abdullah ibn Sina) who had a special attention toward diseases treatments, gathered results of ages of herbal medicine experiments on humans and animals in his book "Al-Qānūn fī Ṭibb" or "The Canon of Medicine", which is a reliable book in Iranian traditional medicine. The aim of this research was to build a reliable list of plants effective against liver and spleen diseases, based on Avicenna's book (volume 2).

Materials And Methods: By studying the monographs, introduced agents that have been effective in liver and spleen diseases were identified. Upon their origin and effectiveness in diseases of the liver, spleen or both, treatments were organized.

Results: From a huge number of drugs, 163 plants from 73 families were found to be effective in treatment of liver and spleen illnesses. In addition, 30 non-herbal agents effective in treatment of liver diseases were detected. The Lamiaceae family have the most effective herbs for treatment of diseases of the liver, spleen or both. Hemp Agrimony, Irsā, and Fūdhanj achieved the highest scores.

Conclusion: The effects of different plants on liver and spleen diseases were indicated in Avicenna's book. Due to the report on the above book, further studies needed specially on the effect of Irsā (Iris ensata) and family Lamiaceae on liver and spleen diseases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448543PMC
April 2019

Effect of Hydroethanolic Extract of L. on Skin Wound Healing Process in Diabetic Male Rats.

Int J Prev Med 2019 12;10:18. Epub 2019 Feb 12.

Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: The aim of this study was to investigate the effect of hydroethanolic L. extract on skin wound healing in diabetic male rats.

Methods: This experimental study was conducted on 49 male Wistar rats weighing 220-250 g divided into 7 groups of 7 each: control (nondiabetic untreated), sham (nondiabetic eucerin-treated), nondiabetic phenytoin (1%)-treated, diabetic untreated, and three diabetic groups treated independently with phenytoin 1%, hydroethanolic extracts 20% or 40%. Diabetes was induced with 60 mg/kg streptozosin in one administration. After anesthesia, 2 × 1 cm wounds were made on the rats' backs and each group was administered with its own respective treatment until the wounds were healed completely. Tissue specimens were prepared for histological examinations. The areas of the wounds were measured every 3 days. The data were analyzed by ANOVA and Tukey's post-hoc test.

Results: The mean duration of wound healing was 27 and 24 days for diabetic untreated and diabetic phenytoin-treated groups, respectively. Wounds were healed completely in nondiabetic untreated, sham, and nondiabetic phenytoin-treated groups on days 23, 24, and 21, respectively. The shortest duration of wound healing was seen in diabetic extract (40%)-treated group (15 days) followed by diabetic (20%)-treated group (18 days). These two groups were found to have the lowest mean wound area during the study with a significant difference from mean wound area in the controls ( < 0.05).

Conclusions: extract significantly promoted wound healing in diabetic rats in comparison with control groups. Although the beneficial mechanism of the promotion of wound healing was not specifically studied, it is believed that the anti-inflammatory and antimicrobial properties of would contribute to this enhanced wound healing.
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http://dx.doi.org/10.4103/ijpvm.IJPVM_276_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390428PMC
February 2019

Effects of lactulose and silymarin on liver enzymes in cirrhotic rats.

Can J Physiol Pharmacol 2017 May 10;95(5):522-529. Epub 2017 Mar 10.

d Department of Pathology, Hamadan University of Medical Sciences, Shahid Fahmideh Boulevard, Hamadan, Iran.

Silymarin, a mixture of antihepatotoxic flavonolignans used in the treatment of liver diseases, and lactulose, a nonabsorbable synthetic disaccharide, were investigated to analyze their probable synergic and healing effects in a hepatic cirrhotic rat model. Liver damage was induced by the administration and subsequent withdrawal of thioacetamide. The significant decrease in liver enzymes and malondialdehyde levels confirmed the curative effects of silymarin and lactulose. In the silymarin + lactulose group, liver enzyme and malondialdehyde levels were significantly reduced compared with those in the thioacetamide group. All treatments led to liver regeneration and triggered enhanced regeneration. Silymarin and lactulose alone or in combination have potent curative effects and reduce thioacetamide-induced liver damage.
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http://dx.doi.org/10.1139/cjpp-2016-0454DOI Listing
May 2017

The protective effect of hydro-alcoholic extract of mangrove ( L.) leaves on kidney injury induced by carbon tetrachloride in male rats.

J Nephropathol 2016 Oct 5;5(4):118-122. Epub 2016 Jun 5.

Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Background: Materials can cause liver and kidney damage which carbon tetrachloride is one of these substances. Medicinal plants and their essential oils and extracts have been used to a large extent as drugs to better control and management of kidney diseases.

Objectives: The aim of this study was to investigate the effect of hydro-alcoholic extract of leaves in the treatment of renal toxicity induced by carbon tetrachloride.

Methods: Forty-two male rats were randomly divided into 6 groups (n = 7): control (taking normal saline, 0.5 ml/day, intraperitoneally; i.p.), sham (taking olive oil, 0.5 ml/day, i.p., single dose), injury induced by carbon tetrachloride (CCl) 1:1 with olive oil, 0.5 ml single dose, i.p.), treated groups 1, 2 and 3: by carbon tetrachloride 1:1 with olive oil, 0.5 ml single dose and 200 mg/kg, 400 mg/kg or 800 mg/kg extract (AME)/ day for 96 hours, i.p.). By direct blood sampling from the heart, the plasma concentrations of lactate dehydrogenase, blood urea nitrogen (BUN), creatinine and liver enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were measured. Kidney sections were prepared from all groups and the histological examinations were performed. The results were analyzed using one-way analysis of variance (ANOVA).

Results: The results indicated the significant ( < 0.05) increase of serum level of lactate dehydrogenase and liver enzymes of AST, ALT and ALP in the group receiving CCl compared with the control group, whereas the treatment with hydro-alcoholic extract of mangrove leaves caused a significant ( < 0.05) decrease in serum levels of these enzymes in rats treated with carbon tetrachloride compared to the control group. Histological investigation of renal tissue sections showed that the treatment with mangrove leaves extract reduced the necrosis, inflammation and also improved the renal tubules.

Conclusions: Carbon tetrachloride has kidney, liver and cardiac toxicities and mangrove extract is able to inhibit the toxicities of carbon tetrachloride.
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http://dx.doi.org/10.15171/jnp.2016.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125057PMC
October 2016

Effects of cannabinoid and glutamate receptor antagonists and their interactions on learning and memory in male rats.

Pharmacol Biochem Behav 2015 Apr 13;131:87-90. Epub 2015 Feb 13.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Introduction: Despite previous findings on the effects of cannabinoid and glutamatergic systems on learning and memory, the effects of the combined stimulation or the simultaneous inactivation of these two systems on learning and memory have not been studied. In addition, it is not clear whether the effects of the cannabinoid system on learning and memory occur through the modulation of glutamatergic synaptic transmission. Hence, in this study, we examined the effects of the simultaneous inactivation of the cannabinoid and glutamatergic systems on learning and memory using a passive avoidance (PA) test in rats.

Materials And Methods: On the test day, AM251, which is a CB1 cannabinoid receptor antagonist; MK-801, which is a glutamate receptor antagonist; or both substances were injected intraperitoneally into male Wistar rats 30min before placing the animal in a shuttle box. A learning test (acquisition) was then performed, and a retrieval test was performed the following day.

Results: Learning and memory in the PA test were significantly different among the groups. The CB1 receptor antagonist improved the scores on the PA acquisition and retention tests. However, the glutamatergic receptor antagonist decreased the acquisition and retrieval scores on the PA task. The CB1 receptor antagonist partly decreased the glutamatergic receptor antagonist effects on PA learning and memory.

Conclusions: These results indicated that the acute administration of a CB1 antagonist improved cognitive performance on a PA task in normal rats and that a glutamate-related mechanism may underlie the antagonism of cannabinoid by AM251 in learning and memory.
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http://dx.doi.org/10.1016/j.pbb.2015.02.005DOI Listing
April 2015

Alteration of pentylenetetrazole-induced seizure threshold by chronic administration of ginger (Zingiber officinale) extract in male mice.

Pharm Biol 2015 May 22;53(5):752-7. Epub 2015 Jan 22.

Department of Biology, Faculty of Basic Science, Bu-Ali Sina University , Hamedan , Iran.

Context: Zingiber officinale Roscoe (Zingiberaceae), or ginger, used in traditional Chinese medicine, has antioxidant activity and neuroprotective effects. The effects of this plant on clonic seizure have not yet been studied.

Objective: The present study evaluated the anticonvulsant effect of ginger in a model of clonic seizures induced with pentylenetetrazole (PTZ) in male mice.

Materials And Methods: The anticonvulsant effect of Z. officinale was investigated using i.v. PTZ-induced seizure models in mice. Different doses of the hydroethanolic extract of Z. officinale (25, 50, and 100 mg/kg) were administered intraperitonal (i.p.), daily for 1 week before induction of PTZ. Phenobarbital sodium (30 mg/kg), a reference standard, was also tested for comparison. The effect of ginger on to the appearance of three separate seizure endpoints, e.g., myoclonic, generalized clonic, and tonic extension phase, was recorded.

Results: Hydroethanolic extract of Z. officinale significantly increased the onset time of myoclonic seizure at doses of 25-100 mg/kg (55.33 ± 1.91 versus 24.47 ± 1.33 mg/kg, p < 0.001) and significantly prevented generalized clonic (74.64 ± 3.52 versus 47.72 ± 2.31 mg/kg, p < 0.001) and increased the threshold for the forelimb tonic extension (102.6 ± 5.39 versus 71.82 ± 7.82 mg/kg, p < 0.01) seizure induced by PTZ compared with the control group.

Discussion And Conclusion: Based on the results, the hydroethanolic extract of ginger has anticonvulsant effects, possibly through an interaction with inhibitory and excitatory systems, antioxidant mechanisms, and oxidative stress inhibition.
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http://dx.doi.org/10.3109/13880209.2014.942789DOI Listing
May 2015

A comparative study on effect of metformin and metformin-conjugated nanotubes on blood glucose homeostasis in diabetic rats.

Eur J Drug Metab Pharmacokinet 2015 Sep 27;40(3):343-8. Epub 2014 Jun 27.

Department of Biology, Faculty of Basic Science, Bu-Ali Sina University, Hamedan, Iran,

Diabetes mellitus is one of the most prevalent metabolic disorders. Carbon nanotubes have the advantage to cross the plasma membrane without damaging the cells, improving the biological effect of a drug and reducing its side effects. In the present study, the effect of metformin and metformin-conjugated nanotubes was investigated on blood glucose level in the streptozotocin-induced male diabetic rats. Diabetes in the animals was induced with a single dose of streptozotocin (60 mg/kg; i.p.) and after 3 days the blood glucose was analyzed. Animals showing fasting blood glucose higher than 250 mg/dL were considered as diabetic rats. The animals were treated with metformin and metformin-conjugated nanotubes (150 mg/kg; p.o.) daily and every 48-h for 1 week. Changes in animals' serum blood glucose level were evaluated daily during the treatment period. The results of this study showed that metformin reduced blood glucose levels in diabetic animals. Metformin-conjugated nanotubes significantly reduced the blood glucose levels in diabetic rats (p < 0.01). There was no significant difference in blood glucose level between metformin and metformin-conjugated nanotubes groups (p > 0.05). However, when both formulations of metformin were administered every 48-h, metformin-conjugated nanotubes reduced glycaemia for a longer time than metformin alone (p < 0.001). This study showed that the metformin-conjugated nanotubes would be able to reduce the blood glucose, prolong drug delivery and efficacy duration in animals which were treated with metformin-conjugated nanotubes compared with metformin alone.
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http://dx.doi.org/10.1007/s13318-014-0213-xDOI Listing
September 2015

Acute administration of ginger (Zingiber officinale rhizomes) extract on timed intravenous pentylenetetrazol infusion seizure model in mice.

Epilepsy Res 2014 Mar 30;108(3):411-9. Epub 2014 Jan 30.

Department of Biology, Faculty of Basic Science, Bu-Ali Sina University, Hamedan, Iran. Electronic address:

Purpose: Zingiber officinale (Zingiberaceae) or ginger, which is used in traditional medicine has antioxidant activity and neuroprotective effects. The effects of this plant on clonic seizure have not yet been studied. The present study evaluated the anticonvulsant effect of ginger in a model of clonic seizures induced with pentylenetetrazole (PTZ) in male mice.

Materials And Methods: The anticonvulsant effect of Z. officinale was investigated using i.v. PTZ-induced seizure models in mice. Different doses of the hydroethanolic extract of Z. officinale (25, 50, and 100mg/kg) were administered intraperitonal (i.p.), 2 and 24h before induction of PTZ. Phenobarbital sodium (30mg/kg), a reference standard, was also tested for comparison. The effect of ginger on to the appearance of three separate seizure endpoints (myoclonic, generalized clonus and forelimb tonic extension phase) was recorded.

Results: The results showed that the ginger extract has anticonvulsant effects in all the experimental treatment groups of seizure tested as it significantly increased the seizure threshold. Hydroethanolic extract of Z. officinale significantly increased the onset time of myoclonic seizure at doses of 25-100mg/kg (p<0.001) and significantly prevented generalized clonic (p<0.001) and increased the threshold for the forelimb tonic extension (p<0.01) seizure 2 and 24h before induction of PTZ compared with control group.

Conclusion: Based on the results the hydroethanolic extract of ginger has anticonvulsant effects, possibly through an interaction with inhibitory and excitatory system, antioxidant mechanisms, oxidative stress and calcium channel inhibition.
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http://dx.doi.org/10.1016/j.eplepsyres.2014.01.008DOI Listing
March 2014

Hypothyroidism improves random-pattern skin flap survival in rats.

J Surg Res 2012 Nov 14;178(1):524-8. Epub 2012 Apr 14.

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

Background: The protective effect of hypothyroidism against ischemic or toxic conditions has been shown in various tissues. We investigated the effect of propylthiouracil (PTU)/methimazole (MMI)-induced hypothyroidism and acute local effect of MMI on the outcome of lethal ischemia in random-pattern skin flaps.

Materials And Methods: Dorsal flaps with caudal pedicles were elevated at midline and flap survival was measured at the seventh day after surgery. The first group, as control, received 1 mL of 0.9% saline solution in the flap before flap elevation. In groups 2 and 3, hypothyroidism was induced by administration of either PTU 0.05% or MMI 0.04% in drinking water. The next four groups received local injections of MMI (10, 20, 50, or 100 μg/flap) before flap elevation. Local PTU injection was ignored due to insolubility of the agent.

Results: Hypothyroidism was induced in chronic PTU- and MMI-treated groups, and animals in these groups showed significant increase in their flap survival, compared to control euthyroid rats (79.47% ± 10.49% and 75.48% ± 12.93% versus 52.26% ± 5.75%, respectively, P < 0.01). Acute local treatment of skin flaps with MMI failed to significantly affect the flap survival.

Conclusion: This study demonstrates for the first time that hypothyroidism improves survival of random-pattern skin flaps in rats.
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http://dx.doi.org/10.1016/j.jss.2012.03.058DOI Listing
November 2012

Involvement of nitric oxide in granisetron improving effect on scopolamine-induced memory impairment in mice.

Brain Res 2012 Jan 9;1429:61-71. Epub 2011 Aug 9.

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

Granisetron, a serotonin 5-HT(3) receptor antagonist, widely used as an antiemetic drug following chemotherapy, has been found to improve learning and memory. In this study, effects of granisetron on spatial recognition memory and fear memory and the involvement of nitric oxide (NO) have been determined in a Y-maze and passive avoidance test. Granisetron (3, 10mg/kg, intraperitoneally) was administered to scopolamine-induced memory-impaired mice prior to acquisition, consolidation and retrieval phases, either in the presence or in the absence of a non-specific NO synthase inhibitor, l-NAME (3, 10mg/kg, intraperitoneally); a specific inducible NO synthase (iNOS) inhibitor, aminoguanidine (100mg/kg); and a NO precursor, l-arginine (750 mg/kg). It is demonstrated that granisetron improved memory acquisition in a dose-dependent manner, but it was ineffective on consolidation and retrieval phases of memory. The beneficial effect of granisetron (10mg/kg) on memory acquisition was significantly reversed by l-NAME (10mg/kg) and aminoguanidine (100mg/kg); however, l-arginine (750 mg/kg) did not potentiate the effect of sub-effective dose of granisetron (3mg/kg) in memory acquisition phase. It is concluded that nitric oxide is probably involved in improvement of memory acquisition by granisetron in both spatial recognition memory and fear memory. This article is part of a Special Issue entitled The Cognitive Neuroscience.
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http://dx.doi.org/10.1016/j.brainres.2011.08.006DOI Listing
January 2012

Atorvastatin improved scopolamine-induced impairment in memory acquisition in mice: involvement of nitric oxide.

Brain Res 2011 Apr 23;1386:89-99. Epub 2011 Feb 23.

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

Unlabelled: Atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, widely used in treatment of hypercholesterolemia, slows the progression of mild-to-moderate Alzheimer's disease. In this study, effects of atorvastatin on acquisition of spatial recognition memory and the involvement of nitric oxide (NO) have been determined in a two-trial recognition Y-maze test and passive avoidance. Atorvastatin (1, 5mg/kg, p.o.) was administered prior to acquisition phase, either in presence or in absence of a non-specific NO synthase inhibitor, L-NAME (3, 10mg/kg, i.p.); a specific inducible NO synthase inhibitor, aminoguanidine (100mg/kg); and a NO precursor, l-arginine (750mg/kg).

Results: Atorvastatin significantly improved memory performance in a dose-dependent manner in acquisition of recognition memory, in both Y-maze and passive avoidance tests. 1) Atorvastatin (5mg/kg) significantly increased both exploration time and number of arm entries in scopolamine-treated mice in Y-maze. 2) The beneficial effects of atorvastatin on memory acquisition were significantly reversed by L-NAME (3mg/kg) and aminoguanidine (100mg/kg). 3) The effects of sub-effective dose of atorvastatin (1mg/kg) on memory acquisition were not potentiated by l-arginine (750mg/kg); 4) Administration of atorvastatin (5mg/kg) significantly increased step-through latency in scopolamine-induced memory-impaired mice. 5) Beneficial effect of atorvastatin on passive avoidance was not reversed by L-NAME (up to 10mg/kg). 6) The effects of sub-effective dose of atorvastatin (1mg/kg) on passive avoidance were not potentiated by l-arginine (750mg/kg). The present study demonstrates that atorvastatin improved both short-spatial recognition memory and fear memory. As this effect is reversed by L-NAME and aminoguanidine in short-term memory acquisition, it is concluded that NO might be involved in spatial memory improvement by atorvastatin.
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http://dx.doi.org/10.1016/j.brainres.2011.02.057DOI Listing
April 2011

Chemical composition and antibacterial activity of essential oils of Tripleurospermum disciforme in three developmental stages.

Pharm Biol 2010 Nov 26;48(11):1280-4. Epub 2010 Aug 26.

Laboratory of Plant Cell Biology, Department of Biology, Bu-Ali Sina University, Hamedan, I.R. Iran.

Context: Tripleurospermum disciforme (C.A. Mey) Schultz Bip. (Asteraceae) is a widespread biennial species which also has traditional medicinal uses. According to the few recent studies, essential oils of this species exhibit anti-inflammatory, antispasmodic, antiseptic, antifungal, antiulcer, and antioxidant activity.

Objective: The chemical compositions of the hydrodistilled oils of T. disciforme of Iranian origin are studied in the stages of prior to flowering, flowering, and post flowering, for the first time. Also, we investigated the antibacterial activities of the oils.

Materials And Methods: The essential oils of air-dried T. disciforme were obtained by hydrodistillation in three different developmental stages and analyzed by gas chromatography-mass spectrometry (GC-MS). The antimicrobial activity of the isolated essential oil, in the three stages, was also investigated against four Gram-positive and four Gram-negative bacteria.

Results: Twenty-one components were identified in the essential oils of T. disciforme, and the highest amount of oil was extracted at the flowering stage. The main component of the species in the flowering stage was β-farnesene (22.46%) and the other major components were β-sesquiphellandrene (17.85%), p-methoxy-β-cyclopropylstyrene (16.64%), heptadecane (10.6%), p-methoxy-humulene oxide (6.88%) and benzene acetaldehyde (9.3%). The MIC of essential oil was evaluated from 4 µL ml(-1) against Staphylococcus subtilis and Bacillus cereus to 22 µL ml(-1) against Citrobacter amalonaticus.

Discussion And Conclusion: This study demonstrates the occurrence of β-farnesene/β-sesquiphellandrene chemotype of T. disciforme in western regions of Iran that are different from previous reports. The findings also showed that the essential oils T. disciforme have excellent antibacterial activities and thus have great potentiality to be used as a resource for natural health products.
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http://dx.doi.org/10.3109/13880201003770143DOI Listing
November 2010

GABAA receptors in the central nucleus of amygdala (CeA) affect on pain modulation.

Brain Res 2008 Nov 24;1241:36-41. Epub 2008 Sep 24.

Department of Biology, School of Basic Sciences, Bu-Ali Sina University, Hamadan, Iran.

The central nucleus of the amygdala (CeA), the nociceptive amygdala, serves as the major output nucleus of the amygdala and participates in receiving and processing pain information. Considering the abundance of GABA(A) receptors in the CeA and also the attributed bidirectional roles for GABA in controlling nociception, we examined the effects of bilateral intra-CeA microinjection of a different dose of the GABA(A) receptor agonist, muscimol, and the GABA(A) receptor antagonist, bicuculline, on pain modulation using a tail-flick test. Adult rats were exposed to intra-CeA microinjection of a selective GABA(A) receptor antagonist, bicuculline, (50,100,200,400 ng/side) or a selective GABA(A) receptor agonist, muscimol, (62.5, 125,250,500 ng/side) and subjected to the tail-flick test. Tail-flick latencies were measured every 5 min after drug microinjection for 60 min. Microinjection of bicuculline and muscimol into the CeA increased and decreased tail-flick latency, respectively in a dose-dependent fashion. The hyperalgesic effect of muscimol (500 ng) microinjected into the CeA was attenuated (P<0.001) by a prior microinjection of bicuculline (50 ng) at the same site. The results of the present study showed that locally released GABA in the CeA is involved in pain modulation and suggests the existence of a GABA(A) mediated inhibitory system in the CeA on pain control.
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http://dx.doi.org/10.1016/j.brainres.2008.09.041DOI Listing
November 2008

Effects of URB597 as an inhibitor of fatty acid amide hydrolase on modulation of nociception in a rat model of cholestasis.

Eur J Pharmacol 2008 Sep 19;591(1-3):132-5. Epub 2008 Jun 19.

Department of Biology, School of Basic Sciences, Bu-Ali Sina University, Hamadan, Iran.

Cholestasis is associated with increased activity of the endogenous opioid system that results in analgesia. Endocannabinoid system can reduce pain sensitivity. The use of inhibitors of endocannabinoid metabolism is a novel means of pharmacologically increasing endocannabinoid levels. Considering the interaction that has been shown between the endogenous opioid and endocannabinoid systems in nociception processing, we studied the effects of URB597, a selective inhibitor of FAAH (fatty acid amide hydrolase), on modulation of nociception in a model of elevated endogenous opioid tone, cholestasis. Cholestasis was induced by ligation of the main bile duct using two ligatures and then transection of the duct at the midpoint between them. Seven days after surgery, tail-flick latencies were measured at 60 min after drug administration. A significant increase (P<0.001) in nociception threshold was observed in cholestatic rats compared to unoperated and sham groups. Administration of URB597 (0.3 mg/kg, i.p.) in cholestatic animals significantly (P<0.001) increased tail-flick latency compared to the vehicle treated cholestatic group. URB597 injection to unoperated and sham groups caused a significant (P<0.05, P<0.05) increase in tail-flick latency compared to their respective vehicle treated groups. The antinociceptive effect of URB597 was blocked by coadministration of a cannabinoid CB(1) receptor antagonist, AM251 (1 mg/kg, i.p.) but not by a cannabinoid CB(2) receptor antagonist, SR144528 (1 mg/kg, i.p.) with URB597. These data showed that URB597 as a FAAH inhibitor potentiates antinociception induced by cholestasis in tail-flick test and that the inhibitory effects of URB597 in this model are mediated by cannabinoid CB(1) and not CB(2) receptors.
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http://dx.doi.org/10.1016/j.ejphar.2008.06.061DOI Listing
September 2008

Involvement of nitrergic and opioidergic systems in the hypothermia induced by cholestasis in rats.

Pathophysiology 2006 Dec 11;13(4):227-32. Epub 2006 Sep 11.

Basic Sciences Research Centre, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background And Aim: Cholestatic animals display abnormal hypothalamic responses to pyrogenic stimuli and decreased febrile response to lipopolysaccharide. The present study was undertaken to determine if obstructive cholestasis was associated with abnormal thermoregulation under thermoneutral conditions.

Methods: Male Sprague-Dawley rats weighing 200-250g were randomly divided into 21 groups. Three sets of seven groups were unoperated control, sham-operated and bile duct-ligated rats. The groups of unoperated control, sham-operated and bile duct-ligated rats were treated with daily administration of isotonic saline solution, N(omega)-nitro-l-arginine methyl ester (l-NAME) (3, 10, or 20mg/kg), naltrexone (10 or 20mg/kg) or aminoguanidine (150mg/kg). Body temperatures were measured before and 1, 3, 5 and 7 days after the surgery.

Results: Bile duct-ligated rats had lower body temperature than sham-operated animals at 3 (P<0.001) and 5 (P<0.01) days after surgery. l-NAME, a non-selective inhibitor of nitric oxide synthase (NOS) (10, 20mg/kg, i.p.) or aminoguanidine, a selective iNOS inhibitor (150mg/kg, i.p.), completely reversed this hypothermia (P>0.05). Naltrexone, a non-selective opioid antagonist (20mg/kg, i.p.), also completely corrected this hypothermia (P>0.05). There was a drop in temperature in the first day after the surgery in sham and BDL groups compared to unoperated controls, which was significant in some groups demonstrating the effect of surgery and anesthetic drugs on the body temperature.

Conclusions: Cholestatic rats show impaired thermoregulation suggesting the involvement of nitrergic and opioidergic systems.
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http://dx.doi.org/10.1016/j.pathophys.2006.08.001DOI Listing
December 2006

Homocysteine alterations in experimental cholestasis and its subsequent cirrhosis.

Life Sci 2005 Apr;76(21):2497-512

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

Homocysteine (Hcy), an intermediate in methionine metabolism, has been proposed to be involved in hepatic fibrogenesis. Impaired liver function can alter Hcy metabolism. The aim of the present study was to determine plasma Hcy alterations in acute obstructive cholestasis and the subsequent biliary cirrhosis. Cholestasis was induced by bile duct ligation and sham-operated and unoperated rats were used as controls. The animals were studied on the days 7th, 14th, 21st and 28th after the operation. Plasma Hcy, cysteine, methionine, nitric oxide (NO) and liver S-adenosyl-methionine (SAM), S-adenosyl-homocysteine (SAH), SAM to SAH ratio and glutathione were measured. Chronic L-NAME treatment was also included in the study. Plasma Hcy concentrations were transiently elevated by the day 14th after bile duct ligation (P < 0.01) and subsequently returned to control levels. Similar relative fluctuations in plasma Hcy were observed in BDL rats after intraperitoneal methionine overload. Plasma methionine, cysteine and nitrite and nitrate were significantly increased after bile duct ligation. SAM to SAH ratio was diminished by the 1st week of cholestasis and remained significantly decreased throughout the study. These events were accompanied by a decrease in GSH to GSSG ratio in the liver. Chronic L-NAME treatment improved SAM to SAH ratio and prevented the elevation of plasma Hcy and methionine (P < 0.05) while couldn't influence the other parameters. In conclusion, this study demonstrates alterations in plasma Hcy and liver SAM and SAH contents in precirrhotic stages and in secondary biliary cirrhosis, for the first time. In addition, we observed that plasma Hcy concentrations in BDL rats follow a distinct pattern of alteration from what has been previously reported in other models of cirrhosis. NO overproduction may contribute to plasma Hcy elevation and liver SAM depletion after cholestasis.
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http://dx.doi.org/10.1016/j.lfs.2004.12.009DOI Listing
April 2005