Implication of nitrergic system in the anticonvulsant effects of ferulic acid in pentylenetetrazole-induced seizures in male mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hossein Amini-Khoei ◽  
Shakiba Nasiri Boroujeni ◽  
Zahra Lorigooini ◽  
Arash Salehi ◽  
Reihaneh Sadeghian ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ferulic Acid ◽  
Effective Dose ◽  
Onset Time ◽  
Seizure Threshold ◽  
Anticonvulsant Effect ◽  
Male Mice ◽  
Neuroprotective Effects ◽  
Nitric Oxide Synthase Inhibitor ◽  
The Brain

Abstract Objectives Seizures are abnormal discharge of neurons in the brain. Ferulic acid (FA) is a phenolic compound with antioxidant and neuroprotective effects. The present study aimed to investigate the role of the nitrergic system in the anticonvulsant effect of FA in pentylenetetrazol (PTZ)-induced seizures in male mice. Methods 64 male Naval Medical Research Institute (NMRI) mice weighing 25–29 g were randomly divided into eight experimental groups (n=8). FA at doses 5, 10, and 40 mg/kg alone and in combination with L-nitro-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor) or L-arginine (L-arg) (nitric oxide [NO] precursor) was administrated (intraperitoneal). PTZ was injected (i.v. route) 30 min after drugs administration (1 mL/min). Seizure onset time was recorded and the nitrite levels of prefrontal cortex and serum were determined by the Griess method. Results FA at doses of 10 and 40 mg/kg significantly increased the seizure threshold as well as reduced the serum and brain NO levels in comparison to the saline-received group. Co-administration of the effective dose of FA (10 mg/kg) plus L-arg significantly decreased the seizure threshold in comparison to the effective dose of FA alone. Co-injection of the sub-effective dose of FA (5 mg/kg) with L-NAME significantly increased the seizure threshold as well as significantly decreased the brain NO level in comparison to the sub-effective dose of FA alone. Conclusions We showed that the nitrergic system, partially at least, mediated the anticonvulsant effect of FA in PTZ-induced seizures in mice. We concluded that L-NAME potentiated while L-arg attenuated the anticonvulsant effect of FA.

scholarly journals Implication of Nitrergic System in the Anticonvulsant Effect of Ferulic Acid in Pentylenetetrazole-induced Seizures in Male Mice

2020 ◽  
Author(s):  
Hossein Amini Khoei ◽  
Shakiba Nasiri Boroujeni ◽  
Zahra Lorigooini ◽  
Arash Salehi ◽  
Reihaneh Sadeghian ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ferulic Acid ◽  
Effective Dose ◽  
Onset Time ◽  
Seizure Threshold ◽  
Anticonvulsant Effect ◽  
Male Mice ◽  
Neuroprotective Effects ◽  
Nitric Oxide Synthase Inhibitor ◽  
Brain Nitric Oxide

Abstract Background and Aim: Given the widespread prevalence of seizures worldwide and the low efficacy of synthetic drugs, studies are needed to find new compounds with appropriate efficacy. Ferulic acid (FA) is a phenolic compound with antioxidant and neuroprotective effects. The aim of present study was to investigate the role of nitrergic system in the anticonvulsant effect of FA in pentylenetetrazol-induced seizures in male mice. Material and Methods: 64 male NMRI mice weighing 25-29 g were randomly divided into 8 experimental groups (n=8). FA at doses 5, 10 and 40 mg / kg alone and in combination with L-NAME (nitric oxide synthase inhibitor) or L-arg (nitric oxide precursor) was administrated (i.p.). PTZ was injected (i.v. route) 30 min after drugs administration. Seizure onset time was recorded and the nitrite levels of prefrontal cortex and serum were determined by Griess Method. Results: FA at doses of 10 and 40 mg / kg significantly increased the seizure threshold as well as reduced the serum and brain nitric oxide levels in comparison to the saline- received group. Co-administration of effective dose of FA (10 mg/kg) plus L-arginine significantly decreased the seizure threshold in compared to the effective dose of FA alone. Co-injection of sub-effective dose of FA (5 mg/kg) with L-NAME significantly increased the seizure threshold as well as significantly decreased the brain nitric oxide level in compared to the sub-effective dose of FA alone.Conclusion: FA partially at least, via modulation of nitrergic system possessed anticonvulsant effect in PTZ-induced seizures in mice.

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.

DIPHENYLHYDANTOIN (DILANTIN®) AFTER 20 YEARS

PEDIATRICS ◽  
1959 ◽  
Vol 23 (1) ◽  
pp. 151-161
Author(s):  
Patrick F. Bray
Keyword(s):  
Good Control ◽  
Side Reaction ◽  
Seizure Threshold ◽  
Anticonvulsant Effect ◽  
Gingival Hyperplasia ◽  
Neurologic Diseases ◽  
Anticonvulsant Medication ◽  
Number Of Patients ◽  
Adequate Dosage ◽  
The Brain

Twenty years ago diphenylhydantoin was introduced for the treatment of epilepsy. It quickly became the most useful anticonvulsant medication because it was effective in preventing seizures and its sedative effect was minimal. The treatment of 84 epileptics has been included in this report with three goals in mind: 1) to show that the drug is generally useful by itself; 2) to point out that diphenylhydantoin is superior to other anticonvulsants in some patients; and 3) to emphasize the need for adequate dosage. Progressive neurologic diseases and fixed structural lesions of the brain are present in a significant number of patients in whom good control of seizure cannot be achieved. Uncommonly one sees sensitivity reactions which are similar to the allergic responses to other medications. Toxic reactions occur frequently if one exceeds the patient's tolerance to the drug but these are readily reversible. The cause of gingival hyperplasia, which is an annoying and common side reaction, was discussed in detail. It seems most likely that this reaction is due primarily to a local toxic effect of diphenylhydantoin as it is secreted in the saliva. The mechanism of action of diphenylhydantoin was discussed in the light of recent and relevant research. The effect of the drug in animals on seizure patterns, seizure threshold and concentration of electrolytes in the brain was reviewed. The basic clue to its primary anticonvulsant effect may be its ability to produce a shift of sodium from inside the cells of the brain to the extracellular space. Other metabolic and humoral effects of diphenylhydantoin were cited and these include its relationship to the pituitary-adrenal system, its ability to lower the permeability of the blood-brain barrier, and its property of increasing the concentration of serotonin in brain tissue. The important anticonvulsants which have been introduced since the advent of diphenylhydantoin were reviewed and emphasis was placed upon the usefulness and limitations in comparison to diphenylhydantoin.

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.

scholarly journals GABAergic Regulation of Cerebral Microvascular Tone in the Rat

1997 ◽  
Vol 17 (9) ◽  
pp. 992-1003 ◽  
Author(s):  
Andrea Fergus ◽  
Kevin S. Lee
Keyword(s):  
Nitric Oxide ◽  
Receptor Agonist ◽  
Computer Assisted ◽  
Local Concentration ◽  
Nitric Oxide Synthase Inhibitor ◽  
Cerebral Microvessels ◽  
Endogenous Gaba ◽  
Synthase Inhibitor ◽  
The Brain

The role of GABA in regulating cerebral microvessels was examined in the parenchyma of the hippocampus and the surface of the neocortex. Microvessels were monitored in in vitro slices using computer-assisted videomicroscopy, and synaptically evoked field responses were simultaneously recorded. γ-Aminobutyric acid (GABA) and the GABAA receptor agonist, muscimol, elicited vasodilation in hippocampal microvessels, whereas the GABAB receptor agonist, baclofen, elicited constriction. The muscimol-induced dilation persisted in the presence of the nitric oxide synthase inhibitor, N-nitro-l-arginine, indicating that this response is not mediated by nitric oxide. Inhibition of neuronal discharge activity with tetrodotoxin did not alter this dilation, but it fully blocked the constrictor response to baclofen. These data suggest that GABAB-mediated, but not GABAA-mediated, responses are dependent on action potential generation. The GABAA receptor antagonists, bicuculline and picrotoxin, elicited constriction, suggesting a tonic dilatory influence by endogenous GABA. Bicuculline-induced constriction was not attenuated by tetrodotoxin. In contrast, these vessels were unresponsive to the GABAB receptor antagonist, 2-hydroxysaclofen. Hippocampal microvessels dilated in response to moderate hypoxia, and this response persisted in the presence of bicuculline, indicating that the hypoxia-induced dilation is not mediated by an action at GABAA receptors. In arterioles located on the surface of the neocortex (i.e., not embedded in the parenchyma of the brain), muscimol elicited vasodilation, whereas bicuculline was ineffective. These results suggest that although these vessels are responsive to GABA, the local concentration of endogenous GABA is insufficient to elicit a tonic effect at rest. These findings raise the possibility that GABA plays a role in local neurovascular signaling in the parenchyma of the brain.

Effects of carbon monoxide on the brain may be mediated by nitric oxide

1996 ◽  
Vol 81 (3) ◽  
pp. 1078-1083 ◽  
Author(s):  
S. Meilin ◽  
G. G. Rogatsky ◽  
S. R. Thom ◽  
N. Zarchin ◽  
E. Guggenheimer-Furman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Oxidative Metabolism ◽  
Combined Treatment ◽  
Physiological Role ◽  
Low Doses ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
The Brain

Carbon monoxide (CO) is known to be a toxic molecule due to the high affinity of hemoglobin for it. However, it has recently been shown that low doses of CO may play a physiological role. The aim of the present study was to examine processes occurring in the brain during exposure to 1,000 parts per million CO that result in an increase in cerebral blood flow (CBF) but are not accompanied by changes in oxidation metabolism. This study was carried out in awake rats with the multiprobe assembly developed in this laboratory for the simultaneous continuous measurement of CBF, intramitochondrial NADH redox levels, direct current potential, and extracellular concentrations of K+, Ca2+, and H+ as well as the electrocorticogram. Exposure to 1,000 parts per million CO in air resulted in an increased CBF without any concomitant changes in any of the other metabolic or ionic parameters measured. This indicates that tissue hypoxia was not the trigger for this vasodilation. Injection of N omega-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor, before exposure to CO effectively blocked the increase in CBF that was observed when the animal was exposed to CO without prior injection of L-NNA. Furthermore, electrocorticographic depression was observed after the combined treatment of L-NNA and CO. In conclusion, exposure to relatively low doses of CO apparently does not have a deleterious effect on oxidative metabolism because the increase in CBF after this exposure is sufficient to prevent changes in oxidative metabolism, as indicated by the fact that NADH levels remained constant. This protective autoregulatory effect may be mediated by nitric oxide.

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