scholarly journals Effect of Lenalidomide on Pentylenetetrazole-Induced Clonic Seizure Threshold in Mice: A Role for N-Methyl-D-Aspartic Acid Receptor/Nitric Oxide Pathway

2021 ◽  
Vol 11 (1) ◽  
pp. 6-13
Author(s):  
Elaheh Asgari Dafe ◽  
Nastaran Rahimi ◽  
Nina Javadian ◽  
Pegah Dejban ◽  
Monika Komeili ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Aspartic Acid ◽  
Structural Analog ◽  
Clonic Seizure ◽  
Seizure Threshold ◽  
Acute Administration ◽  
Mk 801 ◽  
Acid Receptor ◽  
Anticonvulsive Effect

Background and Purpose: Accumulating evidence suggest that lenalidomide, a structural analog of thalidomide, has neuro-modulatory and neuroprotective properties. In the present study, we investigated effects of acute administration of lenalidomide on clonic seizure threshold in mice induced by pentylenetetrazole (PTZ) and possible role of N-methyl-D-aspartic acid receptor (NMDAR) and nitric oxide (NO) pathway.Methods: We have utilized a clonic model of seizure in NMRI mice induced by PTZ to evaluate the potential effect of lenalidomide on seizure threshold. Different doses of lenalidomide (5, 10, 20, and 50 mg/kg, intraperitoneal [i.p.]) were administered 1 hour before PTZ. To evaluate probable role of NMDAR/NO signaling, the non-selective NO synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME; 10 mg/kg, i.p.), neuronal NOS (nNOS) inhibitor 7-nitroindazole (7-NI; 30 mg/kg, i.p.), selective inducible NOS inhibitor aminoguanidine (AG; 100 mg/kg, i.p.), selective NMDAR antagonist MK-801 (0.01 mg/kg, i.p.), and selective NMDAR agonist D-serine (30 mg/kg, i.p.) were injected 15 minutes before lenalidomide.Results: Lenalidomide at 10 and 20 mg/kg significantly elevated the PTZ-induced seizure thresholds. Interestingly, L-NAME (10 mg/kg, i.p), 7-NI (30 mg/kg, i.p), and AG (100 mg/kg, i.p) reversed the anticonvulsive effect of lenalidomide (10 mg/kg). Moreover, treatment with the NMDAR agonist D-serine (30 mg/kg, i.p.) did not alter the anticonvulsive properties of lenalidomide (10 mg/kg, i.p). However, the NMDAR antagonist MK-801 (0.01 mg/kg, i.p) significantly reversed the anticonvulsive effects of lenalidomide (10 mg/kg).Conclusions: Our study demonstrated a role for the NMDAR/NO pathway in the anticonvulsive effects of lenalidomide on the PTZ-induced clonic seizures in mice.

Morphine sensitization in the pentylenetetrazole-induced clonic seizure threshold in mice: Role of nitric oxide and μ receptors

2011 ◽  
Vol 20 (4) ◽  
pp. 602-606 ◽  
Author(s):  
Hamed Shafaroodi ◽  
Nazanin Baradaran ◽  
Leila Moezi ◽  
Siavash Dehpour ◽  
Tina Kabiri ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Clonic Seizure ◽  
Seizure Threshold

Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice: involvement of nitric oxide and N-methyl-d-aspartate receptor

2018 ◽  
Vol 96 (8) ◽  
pp. 742-750 ◽  
Author(s):  
Hossein Amini-Khoei ◽  
Nastaran Kordjazy ◽  
Arvin Haj-Mirzaian ◽  
Shayan Amiri ◽  
Arya Haj-Mirzaian ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nmda Receptor ◽  
Seizure Threshold ◽  
Anticonvulsant Effect ◽  
Acute Administration ◽  
Nmda Receptor Antagonists ◽  
Receptor Antagonists ◽  
Nitrite Level ◽  
Nos Inhibitor ◽  
Neuronal Nos

Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole-induced seizures in mouse considering the possible role of the nitric oxide/N-methyl-d-aspartate (NMDA) pathway. We induced seizure using intravenous administration of pentylenetetrazole. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of subeffective doses of the nonselective nitric oxide synthase (NOS) inhibitor NG-l-arginine methyl ester (10 mg/kg) and the neuronal NOS inhibitor 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of subeffective doses of minocycline (40 mg/kg). We found that inducible NOS inhibitor aminoguanidine (100 mg/kg) had no effect on the antiseizure effect of minocycline. Moreover, l-arginine (60 mg/kg), as a NOS substrate, reduced the anticonvulsant effect of minocycline. We also demonstrated that pretreatment with the NMDA receptor antagonists ketamine (0.5 mg/kg) and MK-801 (0.05 mg/kg) increased the anticonvulsant effect of subeffective doses of minocycline. Results showed that minocycline significantly decreased the hippocampal nitrite level. Furthermore, co-administration of a neuronal NOS inhibitor like NMDA receptor antagonists augmented the effect of minocycline on the hippocampal nitrite level. In conclusion, we revealed that anticonvulsant effect of minocycline might be, at least in part, due to a decline in constitutive hippocampal nitric oxide activity as well as inhibition of NMDA receptors.

Role of AT1 receptors in the renal papillary effects of acute and chronic nitric oxide inhibition

1998 ◽  
Vol 274 (3) ◽  
pp. R760-R766 ◽  
Author(s):  
M. Clara Ortíz ◽  
Lourdes A. Fortepiani ◽  
Francisco M. Ruiz-Marcos ◽  
Noemí M. Atucha ◽  
Joaquín García-Estañ
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Angiotensin Ii ◽  
Chronic Administration ◽  
Acute Administration ◽  
Synthesis Inhibitor ◽  
Renal Vasoconstriction ◽  
Oxide Inhibition ◽  
Stimulation Of

Nitric oxide (NO) is a vasodilator substance controlling renal papillary blood flow (PBF) in the rat. In this study we have evaluated the role of AT1 angiotensin II receptors as modulators of the whole kidney and papillary vasoconstrictor effects induced by the acute or chronic inhibition of NO synthesis. Experiments have been performed in anesthetized, euvolemic Munich-Wistar rats prepared for the study of renal blood flow (RBF) and PBF. In normal rats, acute administration of the NO synthesis inhibitor N ω-nitro-l-arginine methyl ester (l-NAME) increased mean arterial pressure (MAP) and decreased RBF and PBF. Either acute or chronic treatment with the AT1 receptor blocker losartan did not modify the decreases in RBF or PBF secondary to l-NAME. In animals made hypertensive by chronic inhibition of NO, basal MAP was higher, whereas RBF and PBF were lower than in the controls. In these animals, acute or chronic administration of losartan decreased MAP and increased both RBF and PBF significantly. These results indicate that, under normal conditions, the decreases in RBF or PBF induced by the acute inhibition of NO synthesis are not modulated by AT1-receptor stimulation. However, the arterial hypertension, renal vasoconstriction, and reduced PBF present in chronic NO-deficient hypertensive rats is partially due to the effects of angiotensin II, via stimulation of AT1-receptors.

Effects of Modafinil on Clonic Seizure Threshold Induced by Pentylenetetrazole in Mice: Involvement of Glutamate, Nitric oxide, GABA, and Serotonin Pathways

2018 ◽  
Vol 43 (11) ◽  
pp. 2025-2037 ◽  
Author(s):  
Erfan Bahramnjead ◽  
Soheil Kazemi Roodsari ◽  
Nastaran Rahimi ◽  
Payam Etemadi ◽  
Iraj Aghaei ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Clonic Seizure ◽  
Seizure Threshold

Regulation of endometrial blood flow in ovariectomized rats: assessment of the role of nitric oxide

1997 ◽  
Vol 273 (4) ◽  
pp. H2009-H2017
Author(s):  
Ren-Sheng Zhang ◽  
Paul H. Guth ◽  
Oscar U. Scremin ◽  
Rajan Singh ◽  
Shehla Pervin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Vascular Resistance ◽  
Ovariectomized Rats ◽  
Acute Administration ◽  
Arterial Blood ◽  
Independent Mechanism ◽  
Estradiol 17Β ◽  
Endometrial Blood Flow

The purpose of this study was to evaluate the role of nitric oxide (NO) in the maintenance of basal endometrial blood flow of ovariectomized rats and in the increase of endometrial blood flow after administration of estradiol 17β (E2β). Endometrial blood flow was repeatedly measured with the H2 gas clearance technique in ovariectomized rats. N ω-nitro-l-arginine methyl ester (l-NAME) dose dependently reduced basal endometrial blood flow and increased mean arterial blood pressure and endometrial vascular resistance. E2β (1 μg/kg iv) increased endometrial blood flow and reduced endometrial vascular resistance, which peaked by 2 h after the injection. The vasoconstrictive activity of l-NAME (an inhibitor for NO synthesis) was compared with that of phenylephrine (PE, an α-receptor agonist acting through an NO-independent mechanism). Doses ofl-NAME (1 and 3 mg/kg iv) were matched with those of PE (3.2 and 6.4 mg ⋅ kg−1 ⋅ h−1iv), as they induced an approximately equivalent percent increase in basal endometrial vascular resistance. The percent increases of endometrial vascular resistance in E2β-treated animals by the two agents in matched doses were also of a similar magnitude. When animals were first treated with l-NAME or PE, E2β lost the ability to reduce endometrial vascular resistance. Enzyme activity and gene expression of NO synthase in the rat uterine tissue were also examined after E2β treatment, and no significant changes were observed. These data raise doubts about the role of NO in the regulation of endometrial blood flow after acute administration of E2β and suggest that other mechanisms may be involved.

N-Methyl-d-aspartic acid-induced penile erection and yawning: role of hypothalamic paraventricular nitric oxide

1997 ◽  
Vol 328 (2-3) ◽  
pp. 115-123 ◽  
Author(s):  
Maria Rosaria Melis ◽  
Salvatora Succu ◽  
Umberto Iannucci ◽  
Antonio Argiolas
Keyword(s):  
Nitric Oxide ◽  
Aspartic Acid ◽  
Penile Erection

Possible Involvement of Endogenous Opioids and Nitric Oxide in the Anticonvulsant Effect of Acute Chloroquine Treatment in Mice

2017 ◽  
Vol 41 (S1) ◽  
pp. S630-S630
Author(s):  
A. Abkhoo
Keyword(s):  
Nitric Oxide ◽  
Effective Dose ◽  
Clonic Seizure ◽  
Endogenous Opioids ◽  
Seizure Threshold ◽  
Anticonvulsant Effect ◽  
Nitric Oxide Signaling ◽  
Nos Inhibitor ◽  
Neuronal Nos ◽  
Anticonvulsant Effects

IntroductionChloroquine, a 4-aminoquinoline derivative, has long been used for the treatment of malaria and rheumatological disorders, including rheumatoid arthritis and systemic lupus erythematosus. Accumulating evidence now suggests potential use of chloroquine as a neuroprotectant. Studies have shown that nitric oxide (NO) pathway is involved in the chloroquine actions. Considering the fact that nitrergic neurotransmission plays a crucial role in the central nervous system functioning, in the present study we evaluated whether nitrergic system is involved in the anticonvulsant effects of chloroquine in a model of clonicseizure in mice.MethodsClonic seizure threshold was determined by infusion of pentylenetetrazole (PTZ, 0.5%) at a constant rate of 1 mL/min into the tail vein of male Swiss mice (23–29 g). Minimal dose of PTZ (mg/kg of mice weight) needed to induce clonicseizure was considered as an index of seizure threshold.ResultsChloroquine (5 mg/kg, acutely 30 min before test, intraperitoneally), i.p significantly increased the seizure threshold. Acute co-administration of a non-effective dose of the non-selective NO synthase (NOS) inhibitor, L-NAME (L-NG-Nitro-L-arginine methyl ester hydrochloride,5 mg/kg, i.p.) or the selective inhibitor of neuronal NOS, 7-NI (7-nitroindazole, 40 mg/kg, i.p.) with an effective dose of chloroquine (5 mg/kg) inhibited its anticonvulsant effects. Co-administration of a non-effective dose the selective inducible NOS inhibitor, aminoguanidine (100 mg/kg, i.p.) with chloroquine 5 mg/kg did not alter its anticonvulsant effects.ConclusionChloroquine increases the PTZ-induced clonic seizure threshold in mice. We demonstrated for the first time that nitric oxide signaling probably through neuronal NOS could be involved in the anticonvulsant effects of chloroquine in this model of seizure in mice.Disclosure of interestThe author has not supplied his/her declaration of competing interest.

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