Nonsteroidal Anti-inflammatory Drug Oxaprozin is Beneficial Against Seizure-induced Memory Impairment in an Experimental Model of Seizures in Rats: Impact On Oxidative Stress and Nrf2/HO-1 Signaling Pathway

Khatami, Parisa; Mirazi, Naser; Khosravi, Maryam; Bananej, Maryam

doi:10.1007/s12031-022-01967-2

Cited by 4 publications

(3 citation statements)

References 25 publications

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“…In this study, the effect of ART on oxidative stress was investigated using the PTZ kindling model. This model is widely used to induce oxidative stress in experimental animals (Alvi et al 2021;Khatami et al 2022). Repeated doses of PTZ can increase ROS in brain cells and lead to LPO formation (Ilhan et al 2005).…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Effects of Artemisinin on Antiepileptogenic, Antioxidant and Cholinesterase Enzymes in Pentylenetetrazole-induced Kindling Model in Mice.

KOÇAK

Yunusoğlu

Huyut

et al. 2023

Preprint

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Artemisinin (ART) is a compound synthesized from the plant Artemisia annua. This compound has various therapeutic effects and is widely used against malaria. However, ART is known to have modulating effects on GABA (gamma-aminobutyric acid) receptors, which are thought to be responsible for epileptic seizures. This study aimed to evaluate the effects of ART on anti-convulsant, antioxidant, and cholinesterase enzyme activities in pentylenetetrazole (PTZ)-induced kindling model in mice. In the experiment, 6 groups were formed, with seven mice in each group. Mice received a total of 11 intraperitoneal injections of PTZ (35 mg/kg). On the last day of the study, a threat dose of PTZ (75 mg/kg) was administered. In addition, behavioral analysis tests (Locomotor activity and rotarod) and biochemical measurements were performed. Compared with the PTZ group, ART attenuated the severity of the kindling, decreasing the seizure score. ART and VPA reversed increased oxidative stress. Decreased cholinesterase enzymes in PTZ-induced brain increased with ART treatment. While the PTZ application impaired locomotor activity in mice, the ART application provided improvement in locomotor activity. However, no significant difference was found between the groups in the motor performance of the mice. The findings show that ART may have the potential to prevent PTZ-induced oxidative stress, neurochemical changes, behavioral disorders, and seizures.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Effects of Artemisinin on Antiepileptogenic, Antioxidant and Cholinesterase Enzymes in Pentylenetetrazole-induced Kindling Model in Mice.

KOÇAK

Yunusoğlu

Huyut

et al. 2023

Preprint

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“…This model is widely used to induce oxidative stress in experimental animals. 39,40 Repeated doses of PTZ can increase ROS in brain cells and lead to LPO formation. 8 The results of this study supported the hypothesis that PTZ triggers oxidative stress and increases levels of MDA, the end product of LPO.…”

Section: Discussionmentioning

confidence: 99%

Effects of Artemisinin on Anti-epileptogenic, Antioxidant and Cholinesterase Enzymes in Pentylenetetrazole-induced Kindling Model in Mice

Kocak,

Yunusoglu,

Huyut

et al. 2023

Ind. J. Pharm. Edu. Res.

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Background: Artemisinin (ART) is a compound synthesized from the plant Artemisia annua. This compound has various therapeutic effects and is widely used against malaria. However, ART is known to have modulating effects on GABA (gamma-aminobutyric acid) receptors, which are thought to be responsible for epileptic seizures. This study aimed to evaluate the effects of ART on anti-convulsant, antioxidant, and cholinesterase enzyme activities in Pentylenetetrazole (PTZ)-induced kindling model in mice. Materials and Methods: In the experiment, 6 groups were formed, with seven mice in each group. Mice received a total of 11 intraperitoneal injections of PTZ (35 mg/kg). On the last day of the study, a threat dose of PTZ (75 mg/kg) was administered. In addition, behavioral analysis tests (Locomotor activity and rotarod) and biochemical measurements were performed. Results: Compared with the PTZ group, ART attenuated the severity of the kindling, decreasing the seizure score. ART and VPA reversed increased oxidative stress. Decreased cholinesterase enzymes in PTZ-induced brain increased with ART treatment. While the PTZ application impaired locomotor activity in mice, the ART application provided improvement in locomotor activity. However, no significant difference was found between the groups in the motor performance of the mice. Conclusion: The findings show that ART may have the potential to prevent PTZ-induced oxidative stress, neurochemical changes, behavioral disorders, and seizures.

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“…Non steroidal anti-inflammatory drug (NSAIDs) oxaprozinis also reported to have an anti-epileptic effect in rat models [ 38 , 39 ]. But the other predicted NSAIDs, ketoprofen, do not show any anti-epileptic response during in-vivo studies [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Drug repositioning for idiopathic epilepsy using gene expression signature data

Kumar¹

2022

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Epilepsy is one of the most common neurological disorders, affecting millions of patients with a substantial economic and human burden. About 30-40% of epileptic patients remain un-treated after the therapeutic option. Genetic or idiopathic epilepsy count about 40% of total epilepsy patients, showing a maximum percentage for drug-resistant epilepsy. Since the last century basic approach to understanding disease progression and drug discovery has been through the prism, exploring all possible causes and treatment options. Here we report about the gene expression-based drug repositioning study for epilepsy. Epilepsy gene expression data was retrieved from the Gene Expression Omnibus database, while drugs-associated gene expression data was retrieved from the Connectivity map (CMAP). The study predicted309 drug compounds which can alter genetic epilepsy-mediated gene signature using an in-house developed R-script. These compounds were docked against identified epilepsy targets– Voltage-gated sodium channel subunit a2 (Nav1.2); GABA receptor a1-b1; and Voltage-gated calcium channel a1G (Cav3.1)using Carbamazepine, Clonazepam, and Pregabalin as standard drugs, respectively. Twenty-one predicted drug compounds showed better binding affinity than respective standards against the selected epileptic receptors. Among these drug compounds, Ergocalciferol, Oxaprozin, Flunarizine, Triprolidine and Cyproheptadine have been previously reported for anti-epileptic activities and can be potential hits to target idiopathic epilepsy.

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Nonsteroidal Anti-inflammatory Drug Oxaprozin is Beneficial Against Seizure-induced Memory Impairment in an Experimental Model of Seizures in Rats: Impact On Oxidative Stress and Nrf2/HO-1 Signaling Pathway

Cited by 4 publications

References 25 publications

WITHDRAWN: Effects of Artemisinin on Antiepileptogenic, Antioxidant and Cholinesterase Enzymes in Pentylenetetrazole-induced Kindling Model in Mice.

WITHDRAWN: Effects of Artemisinin on Antiepileptogenic, Antioxidant and Cholinesterase Enzymes in Pentylenetetrazole-induced Kindling Model in Mice.

Effects of Artemisinin on Anti-epileptogenic, Antioxidant and Cholinesterase Enzymes in Pentylenetetrazole-induced Kindling Model in Mice

Drug repositioning for idiopathic epilepsy using gene expression signature data

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