Publications by authors named "Faiza Mumtaz"

11 Publications

  • Page 1 of 1

Involvement of nNOS, and α1, α2, β1, and β2 Subunits of Soluble Guanylyl Cyclase Genes Expression in Anticonvulsant Effect of Sumatriptan on Pentylenetetrazole-Induced Seizure in Mice.

Iran J Pharm Res 2020 ;19(4):181-192

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Epileptic seizure is phenomenon of abnormal synchronous neuronal discharge of a set of neurons in brain as a result of neuronal excitation. Evidence shows the nitric oxide (NO) involvement in neuronal excitability. Moreover, the role of cyclic guanosine monophosphate (cGMP) activation in seizure pathogenesis is well-established. Sumatriptan is a selective agonist of 5-Hydroxytryptamine1B/D auto-receptor, has been reassessed for its neuroprotection. This study was aimed to explore the anticonvulsant effect of sumatriptan through possible involvement of NO-cGMP pathway in mice. For this purpose, the protective effect of sumatriptan on PTZ-induced clonic seizure threshold (CST) was measured using NO-cGMP pathway inhibitors including N(G)-nitro-L-arginine (L-NNA, 1, 5, and 10 mg/kg), 7-nitroindazole (7-NI, 30, 45, and 60 mg/kg), aminoguanidine (AG, 30, 50, and 100 mg/kg), methylene blue (MB, 0.1, 0.5, and 1 mg/kg) and sildenafil (5, 10, and 20 mg/kg). The involvement of nitrergic system was further confirmed by measurement of nitrite levels by Griess reaction. The gene expression of neuronal nitric oxide synthase (nNOS) and subunits of soluble guanylyl cyclase (sGC) was studied using qRT-PCR analysis. Acute administration of sumatriptan (1.2 and 0.3 mg/kg) in combination with subeffective doses of NOS, sGC, and phosphodiesterase 5 inhibitors significantly reversed the PTZ-induced CST ( 0.001). The nitrite level in prefrontal cortex was significantly attenuated by sumatriptan ( ≤ 0.01). Furthermore, sumatriptan downregulated the PTZ-induced mRNA expression of nNOS ( ≤ 0.01), α1 ( ≤ 0.001), α2 ( ≤ 0.05), and β1 ( ≤ 0.05) genes in cerebral cortex of mice. In conclusion, the anticonvulsant activity of sumatriptan at least, in part, is mediated through inhibiting NO-cGMP pathway.
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http://dx.doi.org/10.22037/ijpr.2020.112594.13844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019868PMC
January 2020

Antidepressant-like effect of ethanol in mice forced swimming test is mediated via inhibition of NMDA/nitric oxide/cGMP signaling pathway.

Alcohol 2021 May 11;92:53-63. Epub 2021 Feb 11.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

There is evidence for a dramatic relationship between depression and alcohol consumption. Depressed patients may abuse ethanol because this agent reduces the symptoms of depression. In the current study, we aimed to investigate the NMDA/nitric oxide/cGMP pathway in the antidepressant-like effect of ethanol in an animal model of behavioral despair. Animals were subjected to locomotor activity in an open-field test separately, followed by a forced swimming test. During the forced swimming test (FST), ethanol (2 and 2.5 g/kg) significantly decreased the immobility time without altering the locomotor activity of animals. The antidepressant-like effect of ethanol (2.5 g/kg) was reversed by co-administration of N-methyl-D-aspartate (NMDA, 75 mg/kg), L-arginine (750 mg/kg), or sildenafil (5 mg/kg). In contrast, co-administration of MK-801 (0.05 mg/kg), ketamine (1 mg/kg), and ifenprodil (0.5 mg/kg) as antagonists of NMDAR, and NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), 7-nitroindazole (7-NI, 30 mg/kg), and methylene blue (10 mg/kg) as inhibitors of nitric oxide synthase (NOS), or 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) (20 mg/kg), a nitric oxide/cyclic-guanosine monophosphate (NO-cGMP) inhibitor, with a subeffective dose of ethanol (1.5 g/kg), significantly decreased the immobility time in the FST. Furthermore, injection of ethanol 2.5 g/kg alone or 1.5 g/kg with a 7-NI subeffective dose, significantly decreased the nitrite levels in the hippocampus and prefrontal cortex. Hence, it is concluded that blockade of NMDA receptors and the nitric oxide/cyclic-guanosine monophosphate (NO-cGMP) pathway might be involved in the antidepressant-like effect of ethanol in mice.
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http://dx.doi.org/10.1016/j.alcohol.2021.01.005DOI Listing
May 2021

Lithium reverses the effect of opioids on eNOS/nitric oxide pathway in human umbilical vein endothelial cells.

Mol Biol Rep 2020 Sep 4;47(9):6829-6840. Epub 2020 Sep 4.

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

The main challenge of pain management with opioids is development of acute and chronic analgesic tolerance. Several studies on neuronal cells have focused on the molecular mechanisms involved in tolerance such as cyclic AMP (cAMP) activation, and nitric oxide (NO) pathway. However, the effects of opioids on non-neuronal cells and tolerance development have been poorly investigated. Lithium chloride is a glycogen synthase kinase 3β (GSK-3β) inhibitor and exert its effects through modulation of nitric oxide pathway. In this study we examined the effect of lithium on acute/chronic morphine and methadone administration in endothelial cells which express mu opioid receptors. Human umbilical vein endothelial cells (HUVECs) were treated with different doses of morphine, methadone, and lithium for six and 48 h. Then we evaluated cell viability, nitrite and cyclic AMP levels, as well as the expression of endothelial nitric oxide synthase (eNOS) protein using Immunocytochemistry (ICC) assay and phosphorylated GSK-3β enzyme by western blot analysis in cells. Both chronic morphine and methadone treatment increased NO level and eNOS expression in HUVECs. Morphine induced cAMP overproduction after 48 h exposure with cells. Lithium pretreatment (10 mM) in both morphine and methadone received groups significantly reduced nitrite and cAMP levels as well as eNOS expression as compared to the control. The decreased amount of phospho GSK-3β due to the opioid exposure was increased following lithium treatment. Tolerance like pattern may occur in non-neuronal cells with opioid receptors and this study clearly revealed the attenuation of morphine and methadone tolerance like behavior by lithium treatment in HUVECs.
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http://dx.doi.org/10.1007/s11033-020-05740-9DOI Listing
September 2020

Risperidone attenuates acetic acid-induced colitis in rats through inhibition of TLR4/NF-kB signaling pathway.

Immunopharmacol Immunotoxicol 2020 Oct 25;42(5):464-472. Epub 2020 Aug 25.

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

Aim: The purpose of the present study is to explore the anti-inflammatory potential of risperidone in acetic acid-induced rat colitis through inhibition of TLR4/NF-kB pathway.

Methods: Acute colitis induction was done by intra-rectal administration of 2 mL of 4% diluted acetic acid solution. Two h after colitis induction, dexamethasone (2 mg/kg) as standard drugorrisperidone (2, 4 and 6 mg/kg) were administered orally to wistar rats for five consecutive days. 24 h after the last treatment, animals were sacrificed by cervical dislocation. Macroscopic and microscopic damage evaluation was done. Biochemical and ELISA methods were used to assess myeloid peroxidase (MPO) enzyme activity and tumor necrosis factor-α (TNF-α) level respectively. Moreover, immunohistochemistry (IHC) was performed to detect the expression of TLR4 and pNF-kBproteins.

Results: Dexamethasone (2 mg/kg) or risperidone (2, 4 and 6 mg/kg) improved acetic acid-induced macroscopic ( < .001) and microscopic lesions. Additionally, risperidone (2, 4 and 6 mg/kg) inhibited the activity of MPO and TNF-α ( < .01,  < .001) in the colon tissue compared to acetic acid group. Furthermore, bothdexamethasone and risperidone (2, 4 and 6 mg/kg) significantly reduced acetic acid-induced expression of TLR4and pNF-kB proteins ( < .05 < .01 < .001).

Conclusion: The anti-inflammatory effect of risperidone on acetic acid-induced colitis in rats may involve inhibition of TLR4 and NF-kB signaling pathway.
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http://dx.doi.org/10.1080/08923973.2020.1808987DOI Listing
October 2020

Arthrocen, an avocado-soy unsaponifiable agent, improves acetic acid-induced colitis in rat by inhibition of NF-kB signaling pathway.

J Food Biochem 2020 07 22;44(7):e13244. Epub 2020 May 22.

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The goal of the current study was to evaluate the anti-inflammatory effect of Arthrocen against acetic acid-induced colitis in rats. Acute inflammation was produced through intrarectal administration of 2 ml diluted acetic acid (4%) solution. All interventions were carried out for 5 days after colitis induction. Arthrocen was administered orally at doses of 30, 60, and 120 mg kg  day . Then, macroscopic and microscopic studies were performed. Myeloperoxidase (MPO) activity and tumor necrosis factor-α (TNF-α) activity were measured by biochemical and ELISA methods, respectively. Immunohistochemistry was done to investigate the expression of pNF-κB. The results of this study demonstrated that Arthrocen reduced macroscopic and microscopic damage compared to the acetic acid group. Furthermore, Arthrocen decreased the activity of MPO and TNF-α as well as the protein expression of pNF-kB in rat colon tissue. The results of the current study revealed the anti-inflammatory activity of Arthrocen in acetic acid mediated colon inflammation through suppressing the NF-κB pathway. PRACTICAL APPLICATIONS: Inflammatory bowel disease (IBD) is an immune-mediated chronic relapsing disorder affecting the gastrointestinal tract (GIT) characterized by chronic bowel inflammation. A plant-based dietary supplement containing avocado and soy unsaponifiable extracts in a ratio of 1:2 is known as Arthrocen. Arthrocen can be used as a complementary drug beside current drugs in clinical trials for the treatment of IBD.
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http://dx.doi.org/10.1111/jfbc.13244DOI Listing
July 2020

Protective effect of dapsone against renal ischemia-reperfusion injury in rat.

Immunopharmacol Immunotoxicol 2020 Jun 23;42(3):272-279. Epub 2020 Apr 23.

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

Ischemia/reperfusion can cause injury to tissues and compromise functionality of organs due to inflammatory processes. Significantly, development of these effects in kidney tissue has been a challenging issue that leads to acute renal injury. In this study, anti-inflammatory, anti-oxidative, and protective features of dapsone on kidney ischemia/reperfusion injury were investigated. Renal ischemia was induced in rats by bilateral renal arteries clamping for 45 min followed by 24 h reperfusion phase. The effects of different doses of dapsone (1, 3, 10 mg/kg) on ischemia/reperfusion injury in kidney tissue were investigated by targeting BUN, Creatinine, LDH, MDA, MPO, IL-1β, TNF-α, and NFκB. In addition histopathological examination was performed by H&E staining method. Comparing the findings of this study showed significant reduction in BUN and LDH in 10 mg/kg dapsone received groups, and Cr, MDA, and MPO in 3 mg/kg dapsone received groups. The serum level of TNF-α was significantly decreased with both doses of 3 and 10 mg/kg dapsone. The same results were observed in the serum level of IL-1β and NFκB. Besides, remarkable improvement in histological damages was also observed with dapsone treatment. These results support the hypothesis that the positive effects of dapsone on the renal ischemia/reperfusion injury are mediated by modulating inflammatory cascades.
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http://dx.doi.org/10.1080/08923973.2020.1755308DOI Listing
June 2020

Effect of Nebulized Eucalyptus for Preventing Ventilator-associated Pneumonia in Patients Under Mechanical Ventilation: A Randomized Double Blind Clinical Trial.

Altern Ther Health Med 2020 Aug;26(S2):126-130

Background: Pneumonia caused by the ventilator is the most common acquired infection in the intensive care unit (ICU), which increases the morbidity and mortality of the patients. Eucalyptus plant has antiseptic properties that may mollify such morbidity and mortality.

Objective: To assess the effect of Eucalyptus incense on prevention of pneumonia in patients with endotracheal tube in the ICU.

Research Design: A randomized controlled clinical trial with parallel groups of 100 patients undergoing mechanical ventilation.

Setting: An ICU in a teaching hospital.

Interventions: Randomization to received Eucalyptus solution 5% (intervention group = 50) and received 10 cc distilled water as an inhaler 3 times/d (every 8 h/d for 20 min) (control group = 50).

Primary Outcome Measures: The incidence of early and delay pneumonia and pulmonary infections based on clinical pulmonary infection criteria were assessed.

Results: The incidence of late pneumonia was significantly lower in the intervention group compared with control groups (P < .01). The prevalence of Klebsiella, Candida albicans, and Staphylococcus aureus was significantly decreased in the intervention group (P < .01).

Conclusion: The results present study showed that Eucalyptus inhalation is effective in reducing the incidence of pulmonary infection in patients under ventilation.
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August 2020

Dapsone reduced acetic acid-induced inflammatory response in rat colon tissue through inhibition of NF-kB signaling pathway.

Immunopharmacol Immunotoxicol 2019 Dec 17;41(6):607-613. Epub 2019 Oct 17.

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The purpose of this study is to examine the protective effects of Dapsone on inflammation of intestinal tissue through inhibition of NF-kB pathway in acetic acid-induced colitis in rats. Acute colitis was produced by intra-rectal instillation of 2 mL of 4% acetic acid diluted in normal saline. Then, two hours after induction of colitis, DMSO as vehicle, dexamethasone (2 mg/kg) and dapsone (12.5 mg/kg) were given to the animals intraperitoneally (i.p.) and continued for five following days. Evaluation of macroscopic and microscopic damages were done. Myeloid peroxidase enzyme (MPO) activity was measured by a biochemical technique. Moreover, tumor necrosis factor-α (TNF-α) activity was identified by ELISA, and the expression level of pNF-kB protein was evaluated by immunohistochemistry (IHC). Dexamethasone (2 mg/kg) and dapsone (12.5 mg/kg) decreased the macroscopic and microscopic damages compared with acetic acid group ( ˂ .001). Additionally, these agents decreased the activity of MPO ( ˂ .001), TNF-α ( ˂ .001) and the expression level of p-NF-kB ( ˂ .001) in rat colon tissue compared with the acetic acid group. It is proposed that the anti-inflammatory activity of dapsone on acetic acid-induced colitis in rats may involve the inhibition of NF-kB pathway.
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http://dx.doi.org/10.1080/08923973.2019.1678635DOI Listing
December 2019

Cyclosporin A attenuating morphine tolerance through inhibiting NO/ERK signaling pathway in human glioblastoma cell line: the involvement of calcineurin.

EXCLI J 2018 12;17:1137-1151. Epub 2018 Nov 12.

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Cyclosporin A (CsA) is known to have an immunosuppressive action. However, it is also attracting attention due to its effects on the nervous system, such as inhibiting the development and expression of morphine-induced tolerance and dependence through unknown mechanisms. It has been shown that CsA modulates the nitric oxide (NO) synthesis and extracellular signal-regulated kinases (ERK) activation, which are potentially involved in signaling pathways in morphine-induced tolerance in cellular models. Therefore, the current study was designed to evaluate the modulatory role of CsA on the MOR tolerance, by targeting the downstream signaling pathway of NO and ERK using an model. For this purpose, T98G cells were pretreated with CsA, calcineurin autoinhibitory peptide (CAIP), and N-nitro-l-arginine methyl ester (L-NAME) 30 min before 18 h exposure to MOR. Then, we analyzed the intracellular cyclic adenosine monophosphate (cAMP) levels and also the expression of phosphorylated ERK and nitric oxide synthase (nNOS) proteins. Our results showed that CsA (1 nM, 10 nM, and 100 nM) and CAIP (50 µM) have significantly reduced cAMP and nitrite levels as compared to MOR-treated (2.5 µM) T98G cells. This clearly revealed the attenuation of MOR tolerance by CsA. The expression of nNOS and p-ERK proteins were down-regulated when the T98G cells were pretreated with CsA (1 nM, 10 nM, and 100 nM), CAIP (50 µM), and L-NAME (0.1 mM) as compared to MOR. In conclusion, the CsA pretreatment had a modulatory role in MOR-induced tolerance, which was possibly mediated through NO/ERK signaling pathway.
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http://dx.doi.org/10.17179/excli2018-1693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341459PMC
November 2018

Neurobiology and consequences of social isolation stress in animal model-A comprehensive review.

Biomed Pharmacother 2018 Sep 22;105:1205-1222. Epub 2018 Jun 22.

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

The brain is a vital organ, susceptible to alterations under genetic influences and environmental experiences. Social isolation (SI) acts as a stressor which results in alterations in reactivity to stress, social behavior, function of neurochemical and neuroendocrine system, physiological, anatomical and behavioral changes in both animal and humans. During early stages of life, acute or chronic SIS has been proposed to show signs and symptoms of psychiatric and neurological disorders such as anxiety, depression, schizophrenia, epilepsy and memory loss. Exposure to social isolation stress induces a variety of endocrinological changes including the activation of hypothalamic-pituitary-adrenal (HPA) axis, culminating in the release of glucocorticoids (GCs), release of catecholamines, activation of the sympatho-adrenomedullary system, release of Oxytocin and vasopressin. In several regions of the central nervous system (CNS), SIS alters the level of neurotransmitter such as dopamine, serotonin, gamma aminobutyric acid (GABA), glutamate, nitrergic system and adrenaline as well as leads to alteration in receptor sensitivity of N-methyl-D-aspartate (NMDA) and opioid system. A change in the function of oxidative and nitrosative stress (O&NS) mediated mitochondrial dysfunction, inflammatory factors, neurotrophins and neurotrophicfactors (NTFs), early growth response transcription factor genes (Egr) and C-Fos expression are also involved as a pathophysiological consequences of SIS which induce neurological and psychiatric disorders.
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http://dx.doi.org/10.1016/j.biopha.2018.05.086DOI Listing
September 2018

Thalidomide attenuates the development and expression of antinociceptive tolerance to μ-opioid agonist morphine through l-arginine-iNOS and nitric oxide pathway.

Biomed Pharmacother 2017 Jan 26;85:493-502. Epub 2016 Nov 26.

Department of Pharmacology, School of Medicine, International Campus, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Morphine is a μ-opioid analgesic drug which is used in the treatment and management of chronic pain. However, due to development of antinociceptive tolerance its clinical use is limited. Thalidomide is an old glutamic acid derivative which recently reemerged because of its potential to counteract a number of disorders including neurodegenerative disorders. The potential underlying mechanisms and effects of thalidomide on morphine-induced antinociceptive tolerance is still elusive. Hence, the present study was designed to explore the effect of thalidomide on the development and expression of morphine antinociceptive tolerance targeting l-arginine-nitric oxide (NO) pathway in mice and T98G human glioblastoma cell line. When thalidomide was administered in a dose of 17.5mg/kg before each dose of morphine chronically for 5days it prevented the development of antinociceptive tolerance. Also, a single dose of thalidomide 20mg/kg attenuated the expression phase of antinociceptive tolerance. The protective effect of thalidomide was augmented in development phase when co-administration with NOS inhibitors like L-NAME (non- selective NOS inhibitor; 2mg/kg) or aminoguanidine (selective inducible NOS inhibitor; 50mg/kg). Also, the reversal effect of thalidomide in expression phase was potentiated when concomitantly administrated with L-NAME (5mg/kg) or aminoguanidine (100mg/kg). Co-administration of ODQ (a guanylyl cyclase inhibitor) 10mg/kg in developmental phase or 20mg/kg in expression phase also progressively increased the pain threshold. In addition, thalidomide (20μM) also significantly inhibited the overexpression of iNOS gene induced by morphine (2.5μM) in T98G cell line. Hence, our findings suggest that thalidomide has protective effect both in the development and expression phases of morphine antinociceptive tolerance. It is also evident that this effect of thalidomide is induced by the inhibition of NOS enzyme predominantly iNOS.
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http://dx.doi.org/10.1016/j.biopha.2016.11.056DOI Listing
January 2017