Publications by authors named "Sadaf Nezamoleslami"

7 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

Glatiramer acetate treatment inhibits inflammatory responses and improves survival in a mice model of cecal ligation and puncture-induced sepsis.

J Basic Clin Physiol Pharmacol 2021 Feb 9. Epub 2021 Feb 9.

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

Objectives: Sepsis is a clinical crisis which has been considered as one of the important causes of mortality across the world. We hypothesized that modulation of hyper-inflammatory phase of sepsis pathophysiology can lead to protective effects on survival outcome. Glatiramer acetate (GA) is a neuroprotective drug commonly used in multiple sclerosis (MS). GA is characterized by immunom activity via regulation of innate and adaptive immunity. This study was designed to evaluate the acute treatment with GA on initial inflammatory response-induced mortality in septic mice.

Methods: Cecal ligation and puncture (CLP) model was operated on male mice as a model of Polymicrobial sepsis. GA was administrated intraperitoneally after the sepsis induction at doses of 0.5, 1, and 2 mg/kg in three treatment groups. To investigate the effect of GA on short-term survival, septic mice were observed during 72 h after CLP. Serum levels of TNF-α, IL-1β, and IL-6 as pro-inflammatory cytokines and also IL-10 as a critical anti-inflammatory cytokine were analysed. To consider sepsis-induced acute kidney injury, renal functional biomarkers and histopathological changes was assessed.

Results: GA treatment significantly improved survival rate at doses of 1, and 2 mg/kg. Survival improvement was accompanied by remarkable reduction in the pro-inflammatory cytokines and enhanced production of IL-10. GA showed to have protective effects on renal function as well.

Conclusions: Immunomodulatory and anti-inflammatory properties of GA resulted in increase in survival rate and decrease in inflammatory markers in mice model of cecal ligation and puncture-induced sepsis.
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http://dx.doi.org/10.1515/jbcpp-2020-0303DOI Listing
February 2021

Protective Effects of Spermidine Against Cirrhotic Cardiomyopathy in Bile Duct-Ligated Rats.

J Cardiovasc Pharmacol 2020 09;76(3):286-295

*Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; and †Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Cirrhotic cardiomyopathy is a critical factor that causes morbidity and mortality in crucial conditions such as liver transplantation. In animal model, the common pathophysiologic mechanisms of cirrhotic cardiomyopathy are similar to those associated with bile duct ligation (BDL). Overproduction of inflammatory and oxidant markers plays a crucial role in cirrhotic cardiomyopathy. Spermidine, a multifunctional polyamine, is known for its antioxidant and anti-inflammatory effects. In this study, we investigated the effects of spermidine on development of cirrhotic cardiomyopathy in BDL rats. Rats were randomly housed in 6 groups. Except the normal and sham groups, BDL was performed for all the control and spermidine groups. Seven days after operation, 3 different doses of spermidine (5, 10 and 50 mg/kg) were administrated until day 28, in spermidine groups. At the end of the fourth week, the electrocardiography (ECG) and papillary muscle isolation were performed. The serum level of tumor necrosis factor-a (TNF-α), interleukin-1β (IL-1β), and IL-10 and cardiac level of superoxide dismutase, glutathione (GSH). and malondialdehyde (MDA) were assessed. Furthermore, the nuclear factor-κB (NF-κB) expression was assessed by western blot. Cardiac histopathological changes were monitored. The serum levels of magnesium (Mg) and potassium (K) were investigated. Control group, exhibited exaggerated signs of cirrhotic cardiomyopathy in comparison with the sham group. Co-administration of spermidine at the dose of 10 mg/kg in BDL rats significantly improved the cardiac condition, reduced the inflammatory mediators, and increased antioxidant enzymes. In addition, the histopathologic findings were in accordance with the other results of the study. Besides, there was no significant alteration in serum levels of Mg and K. This study demonstrates that spermidine at the dose of 10 mg/kg significantly improved the cirrhotic cardiomyopathy in BDL model in rats.
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http://dx.doi.org/10.1097/FJC.0000000000000872DOI Listing
September 2020

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

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

Cardioprotective effects of dapsone against doxorubicin-induced cardiotoxicity in rats.

Cancer Chemother Pharmacol 2020 03 8;85(3):563-571. Epub 2020 Jan 8.

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

Purpose: It has been supposed that cardiac toxicity of doxorubicin is due to its production of free radicals and inflammatory cytokines. Dapsone, an antibiotic drug which is the principal in a multidrug regimen for the treatment of leprosy, is a sulfone with anti-inflammatory and antioxidant immunosuppressive properties. Therefore, we designed this study to investigate the possible effects of dapsone on doxorubicin-induced cardiotoxicity.

Methods: Male rats were administrated doxorubicin (2.5 mg/kg) and dapsone (1, 3, 10 mg/kg) intraperitoneally six times in 2 weeks. Then electrocardiographic (ECG) parameters (QRS complexes, RR and QT intervals) alternation, papillary muscle contraction and excitation, and histopathological changes were assessed. Also, the heart tissue levels of malondialdehyde (MDA) as oxidant factor and superoxide dismutase (SOD) as antioxidant enzyme, tumor necrosis factor-alpha (TNF-α) and serum level of CK-MB were analyzed.

Results: Administration of dapsone with doxorubicin significantly reversed alterations induced by doxorubicin in serum levels of CK-MB, ECG parameters, papillary muscle contractility and excitation. Furthermore, the measurement of MDA, SOD and TNF-α tissue level indicated that dapsone significantly reduced oxidative stress and inflammation. These findings were consistent with histopathological analysis.

Conclusion: Dapsone exerts cardioprotective effects on doxorubicin-induced cardiotoxicity through its anti-inflammatory and antioxidant mechanism.
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http://dx.doi.org/10.1007/s00280-019-04019-6DOI Listing
March 2020

Glatiramer acetate attenuates renal ischemia reperfusion injury in rat model.

Exp Mol Pathol 2020 02 4;112:104329. Epub 2019 Nov 4.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, P.O. Box 13145-784, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, P.O. Box 13145-784, Iran. Electronic address:

Chronic renal failure can ultimately lead to kidney transplantation. Renal transplantation is associated with ischemia-reperfusion injury (I/R). The subsequent processes of kidney I/R can lead to irreversible damages to the kidney tissue. Glatiramer acetate is an immunomodulatory drug for the treatment of multiple sclerosis (MS) and the anti-inflammatory effects of this drug have already been proven in some inflammatory models. The purpose of this study was to evaluate the protective effects of Glatiramer on reducing the damages arising from kidney ischemia-reperfusion. In this study, 35 Wistar rats were used which divided into 5 groups: sham, control (I/R), I/R + Glatiramer 0.5 mg/kg, I/R + Glatiramer 1 mg/kg, I/R + Glatiramer 2 mg/kg. Renal arteries were clamped bilaterally for 45 min, then the clamps were removed and the reperfusion process continued to 24 h. In the following, serum and kidneys were separated for analysis. In the control group, serum levels of LDH, inflammatory factor TNF-α and renal functional markers such as BUN and Creatinine were remarkably increased, but in the treatment groups, especially in Glatiramer 2 mg/kg received group, a significant decrease in these factors was observed. Tissue concentration of MDA was reduced following Glatiramer treatment. Besides, Glatiramer attenuated the increased kidney level of NF-κB protein using immunohistochemical assay. NFkB migration to the nucleolus increases inflammatory cytokines production. The anti-inflammatory factor, IL-10, in serum was significantly increased in the treatment group of Glatiramer 2 mg/kg. Furthermore, Glatiramer decreased renal tissue injury score according to the histopathological study. These results demonstrate that Glatiramer may play protective effects in kidney ischemia-reperfusion injury by reducing inflammatory and oxidative damages.
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http://dx.doi.org/10.1016/j.yexmp.2019.104329DOI Listing
February 2020