Lacosamide improves biochemical, genotoxic, and mitochondrial parameters after PTZ‐kindling model in mice

Lazzarotto, Letícia; Pflüger, Pricila; Regner, Gabriela Gregory; Santos, Fabiana Lopes dos; Aguirre, Débora Gonçalves; Brito, Verônica Bidinotto; Moura, Dinara Jaqueline; Santos, Fernanda Marcelia Dos; Picada, Jaqueline Nascimento; Parmeggiani, Belisa; Frusciante, Marina Rocha; Leipnitz, Guilhian; Pereira, Patrı́cia

doi:10.1111/fcp.12598

Cited by 9 publications

(5 citation statements)

References 52 publications

(59 reference statements)

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“…LCM decreased free radicals and SOD activity and was able to increase CAT activity. LCM improved the enzymatic mitochondrial activity of complex I-III and the activity of complex II [152].…”

Section: Animal Studiesmentioning

confidence: 96%

Oxidative Stress and Neurodegeneration in Animal Models of Seizures and Epilepsy

Łukawski

Czuczwar

2023

Antioxidants

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Free radicals are generated in the brain, as well as in other organs, and their production is proportional to the brain activity. Due to its low antioxidant capacity, the brain is particularly sensitive to free radical damage, which may affect lipids, nucleic acids, and proteins. The available evidence clearly points to a role for oxidative stress in neuronal death and pathophysiology of epileptogenesis and epilepsy. The present review is devoted to the generation of free radicals in some animal models of seizures and epilepsy and the consequences of oxidative stress, such as DNA or mitochondrial damage leading to neurodegeneration. Additionally, antioxidant properties of antiepileptic (antiseizure) drugs and a possible use of antioxidant drugs or compounds in patients with epilepsy are reviewed. In numerous seizure models, the brain concentration of free radicals was significantly elevated. Some antiepileptic drugs may inhibit these effects; for example, valproate reduced the increase in brain malondialdehyde (a marker of lipid peroxidation) concentration induced by electroconvulsions. In the pentylenetetrazol model, valproate prevented the reduced glutathione concentration and an increase in brain lipid peroxidation products. The scarce clinical data indicate that some antioxidants (melatonin, selenium, vitamin E) may be recommended as adjuvants for patients with drug-resistant epilepsy.

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Section: Animal Studiesmentioning

confidence: 96%

Oxidative Stress and Neurodegeneration in Animal Models of Seizures and Epilepsy

Łukawski

Czuczwar

2023

Antioxidants

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“…Given that the extract reversed these changes, these findings suggest antioxidant properties and confirm previous studies demonstrating a strong antioxidant potential of P. biglobosa extract ( Banwo et al, 2020 ; Musara et al, 2020 ). Furthermore, flavonoids and polyphenols are known to reduce the formation of reactive oxygen species and free radicals ( Sahu et al, 2020 ; Lazzarotto et al, 2021 ). The abundance of these secondary metabolites in the extract could explain its antioxidant properties.…”

Section: Discussionmentioning

confidence: 99%

Aqueous extract of Parkia biglobosa (Jacq.) R. Br. (Fabaceae) exerts antiepileptogenic, anti-amnesic, and anxiolytic-like effects in mice via mechanisms involving antioxidant and anti-inflammatory pathways

et al. 2022

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Parkia biglobosa (Jacq.) R. Br. (Fabaceae) is a widely distributed tree, used in traditional medicine to treat amebiasis, hookworm infection, ascariasis, asthma, sterility, dental pain, headaches, cardiac disorders, and epilepsy. To date, no study on the effect of an aqueous extract of P. biglobosa on epileptogenesis and associated neuropsychiatric disorders has been undertaken. Therefore, this study aimed to investigate antiepileptogenic-, antiamnesic-, and anxiolytic-like effects of an aqueous extract of P. biglobosa using pentylenetetrazole (PTZ)-induced kindling in mice. Animals were divided into six groups of eight mice each. Thus, a PTZ group received distilled water (10 ml/kg, per os), a positive control group received sodium valproate (300 mg/kg, p.o.), and three test groups received the aqueous extract of P. biglobosa (80, 160, and 320 mg/kg, p.o.).In addition, a control group of eight mice receiving distilled water (10 ml/kg, p.o.) was formed. The treatments were administered to mice, 60 min before administration of PTZ (20 mg/kg, i.p.). These co-administrations were performed once daily, for 22 days. The number and duration of seizures (stages 1, 2, 3, and 4 of seizures) exhibited by each mouse were assessed for 30 min during the treatment period. Twenty-four hours following the last administration of the treatments and PTZ, novel object recognition and T-maze tests were performed to assess working memory impairment in mice, while the open field test was performed to assess anxiety-like behavior. After these tests, the animals were sacrificed, and the hippocampi were collected for biochemical and histological analysis. During the period of PTZ-kindling, the extract at all doses completely (p < 0.001) protected all mice against stages 3 and 4 of seizures when compared to sodium valproate, a standard antiepileptic drug. The extract also significantly (p < 0.001) attenuated working memory impairment and anxiety-like behavior. In post-mortem brain analyses, the extract significantly (p < 0.001) increased γ-aminobutyric acid (GABA) level and reduced oxidative stress and inflammation. Histological analysis showed that the aqueous extract attenuated neuronal degeneration/necrosis in the hippocampus. These results suggest that the extract is endowed with antiepileptogenic-, anti-amnesic-, and anxiolytic-like effects. These effects seem to be mediated in part by GABAergic, antioxidant, and anti-inflammatory mechanisms. These results suggest the merit of further studies to isolate the bioactive molecules responsible for these potentially therapeutically relevant effects of the extract.

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“…It has been well documented that oxidative stress plays a major role in epilepsy (39) and depression (40). Epilepsyrelated mitochondrial dysfunction and brain damage were attributed to oxidative stress and neuroinflammation in animal studies (41,42) which might be primary mechanisms for dexpanthenol. Unlike epilepsy, oxidative stress plays a dual role in depression.…”

Section: Discussionmentioning

confidence: 99%

The Antiepileptic and Antidepressant-Like Effects of Dexpanthenol in Female Swiss Albino Mice

İnan

AÇIKGÖZ

2022

Clinical and Experimental Health Sciences

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Objective: Oxidative stress is one of the main mechanisms of epilepsy and depression. Based on our information, behavioral effects of dexpanthenol in animals have not yet been demonstrated. Dexpanthenol itself is a topical medicine to restore skin barrier against infections caused by microorganisms which also stimulates the peristaltic movements in the gut when administered parenterally; however since it is cheap and easy to use with minor side effects, the main idea of the current research was to evaluate whether dexpanthenol has an antiepileptic and/or antidepressant-like effects.Methods: A group of female Swiss albino mice (25-30 g) were injected with dexpanthenol (ip, N = 8) or saline (ip, N = 8), and 30 min later pentylenetetrazole (65 mg/kg, ip)-induced convulsions were determined for 30 min. In addition, another group of mice were again injected with dexpanthenol (500 mg/kg, ip, N = 8) or saline (ip, N = 8) and immobility time were evaluated in the forced swim test. Finally, mouse righting reflex test was used to assess the possible changes in motor coordination.Results: Our data showed that dexpanthenol, at the dose of 500 mg/kg displayed significant antiepileptic and antidepressant-like effects without affecting motor behavior. Conclusions:A common low-cost topical drug for various skin disorders that can also be given parenterally for motility regulation has an antiepileptic and antidepressant-like activity in mice.

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Lacosamide improves biochemical, genotoxic, and mitochondrial parameters after PTZ‐kindling model in mice

Cited by 9 publications

References 52 publications

Oxidative Stress and Neurodegeneration in Animal Models of Seizures and Epilepsy

Oxidative Stress and Neurodegeneration in Animal Models of Seizures and Epilepsy

Aqueous extract of Parkia biglobosa (Jacq.) R. Br. (Fabaceae) exerts antiepileptogenic, anti-amnesic, and anxiolytic-like effects in mice via mechanisms involving antioxidant and anti-inflammatory pathways

The Antiepileptic and Antidepressant-Like Effects of Dexpanthenol in Female Swiss Albino Mice

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