Anticonvulsant effect of sodium cyclamate and propylparaben on pentylenetetrazol‐induced seizures in zebrafish

Pisera‐Fuster, Antonella; Otero, Sofía; Talevi, Alan; Bruno-Blanch, Luis E.; Bernabeu, Ramón

doi:10.1002/syn.21961

Cited by 13 publications

(4 citation statements)

References 43 publications

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“…Zebrafish can be utilized to investigate the pathogenesis of epilepsy, screening of anti-epileptic drugs, validation of target and most importantly can be modeled into novel seizure model recapitulating the clinical phenotype. Compared to rodents seizure model, zebrafish seizure model possesses a benefits of minimal drugs requirement, shorter duration of assays, resemblance and easy quantification of seizure-like behavior, possibility of recording abnormal neuronal discharge by electroencephalography (EEG) and its transparent nature ( Buenafe et al, 2013 ; Pisera-Fuster et al, 2017 ; Zhang et al, 2020 ). Despite the availability of Kainic acid ( Mussulini et al, 2018 ), PTZ ( Mussulini et al, 2013 ) and Pilocarpine ( Paudel et al, 2020e ) induced seizure model in adult zebrafish, no earlier study has reported a longitudinal (10 days) chronic seizure model in adult zebrafish.…”

Section: Discussionmentioning

confidence: 99%

Anti-High Mobility Group Box-1 Monoclonal Antibody Attenuates Seizure-Induced Cognitive Decline by Suppressing Neuroinflammation in an Adult Zebrafish Model

2021

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Epilepsy is a chronic brain disease afflicting around 70 million global population and is characterized by persisting predisposition to generate epileptic seizures. The precise understanding of the etiopathology of seizure generation is still elusive, however, brain inflammation is considered as a major contributor to epileptogenesis. HMGB1 protein being an initiator and crucial contributor of inflammation is known to contribute significantly to seizure generation via activating its principal receptors namely RAGE and TLR4 reflecting a potential therapeutic target. Herein, we evaluated an anti-seizure and memory ameliorating potential of an anti-HMGB1 monoclonal antibody (mAb) (1, 2.5 and 5 mg/kg, I.P.) in a second hit Pentylenetetrazol (PTZ) (80 mg/kg, I.P.) induced seizure model earlier stimulated with Pilocarpine (400 mg/kg, I.P.) in adult zebrafish. Pre-treatment with anti-HMGB1 mAb dose-dependently lowered the second hit PTZ-induced seizure but does not alter the disease progression. Moreover, anti-HMGB1 mAb also attenuated the second hit Pentylenetetrazol induced memory impairment in adult zebrafish as evidenced by an increased inflection ration at 3 and 24 h trail in T-maze test. Besides, decreased level of GABA and an upregulated Glutamate level was observed in the second hit PTZ induced group, which was modulated by pre-treatment with anti-HMGB1 mAb. Inflammatory responses occurred during the progression of seizures as evidenced by upregulated mRNA expression of HMGB1, TLR4, NF-κB, and TNF-α, in a second hit PTZ group, which was in-turn downregulated upon pre-treatment with anti-HMGB1 mAb reflecting its anti-inflammatory potential. Anti-HMGB1 mAb modulates second hit PTZ induced changes in mRNA expression of CREB-1 and NPY. Our findings indicates anti-HMGB1 mAb attenuates second hit PTZ-induced seizures, ameliorates related memory impairment, and downregulates the seizure induced upregulation of inflammatory markers to possibly protect the zebrafish from the incidence of further seizures through via modulation of neuroinflammatory pathway.

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Section: Discussionmentioning

confidence: 99%

Anti-High Mobility Group Box-1 Monoclonal Antibody Attenuates Seizure-Induced Cognitive Decline by Suppressing Neuroinflammation in an Adult Zebrafish Model

2021

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“…In addition, zebrafish larvae develop a spontaneous swimming pattern at 5 days post-fertilization (dpf), making it an appropriate model organism to study neurobehavior under seizures . Regarding epilepsy research, the zebrafish model offers the advantages of resemblance to seizure-like phenotypes and the possibility of electroencephalography (EEG) assays, making it preferable in preclinical epilepsy research, − especially for early stage screening of anti-epileptic agents. − …”

Section: Introductionmentioning

confidence: 99%

Schaftoside Suppresses Pentylenetetrazol-Induced Seizures in Zebrafish via Suppressing Apoptosis, Modulating Inflammation, and Oxidative Stress

Dang

Paudel

Yang

et al. 2021

ACS Chem. Neurosci.

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The lack of disease-modifying therapeutic strategies against epileptic seizures has caused a surge in preclinical research focused on exploring and developing novel therapeutic candidates for epilepsy. Compounds from traditional Chinese medicines (TCMs) have gained much attention for a plethora of neurological diseases, including epilepsy. Herein, for the first time, we evaluated the anticonvulsive effects of schaftoside (SS), a TCM, on pentylenetetrazol (PTZ)-induced epileptic seizures in zebrafish and examined the underlying mechanisms. We observed that SS pretreatments significantly suppressed seizure-like behavior and prolonged the onset of seizures. Zebrafish larvae pretreated with SS demonstrated downregulation of c-fos expression during seizures. PTZ-induced upregulation of apoptotic cells was decreased upon pretreatment with SS. Inflammatory phenomena during seizure progression including the upregulation of interleukin 6 (IL-6), interleukin 1 beta (IL-1β), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were downregulated upon pretreatment with SS. The PTZ-induced recruitment of immunocytes was in turn reduced upon SS pretreatment. Moreover, SS pretreatment modulated oxidative stress, as demonstrated by decreased levels of catalase (CAT) and increased levels of glutathione peroxidase-1a (GPx1a) and manganese superoxide dismutase (Mn-SOD). However, pretreatment with SS modulated the PTZ-induced downregulation of the relative enzyme activity of CAT, GPx, and SOD. Hence, our findings suggest that SS pretreatment ameliorates PTZ-induced seizures, suppresses apoptosis, and downregulates the inflammatory response and oxidative stress, which potentially protect against further seizures in zebrafish.

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“…It is confirmed that embryonic exposure to PrP triggered anxiety-like neurobehavioral response in zebrafish, which is correlated with oxidative-stress-induced apoptosis in the head of the larvae [ 27 ]. Nevertheless, PrP was suggested to reduce the excitability of hippocampal neurons in rats [ 62 ], and to have anticonvulsant effects on pentylenetetrazol-induced seizures in zebrafish [ 63 ], demonstrating the potential for use in anticonvulsant drugs. In this study, cell cavitation, cytomorphosis and blurred cell boundaries were found in the brain of mosquitofish, the deleterious effects of PrP on the physiological function of brain should be noteworthy to illuminate the safety and toxicity mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Endocrine Disruption of Propylparaben in the Male Mosquitofish (Gambusia affinis): Tissue Injuries and Abnormal Gene Expressions of Hypothalamic-Pituitary-Gonadal-Liver Axis

Song

et al. 2023

IJERPH

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Propylparaben (PrP) is a widely used preservative that is constantly detected in aquatic environments and poses a potential threat to aquatic ecosystems. In the present work, adult male mosquitofish were acutely (4d) and chronically (32d) exposed to environmentally and humanly realistic concentrations of PrP (0, 0.15, 6.00 and 240 μg/L), aimed to investigate the toxic effects, endocrine disruption and possible mechanisms of PrP. Histological analysis showed time- and dose-dependent manners in the morphological injuries of brain, liver and testes. Histopathological alterations in the liver were found in 4d and severe damage was identified in 32d, including hepatic sinus dilatation, cytoplasmic vacuolation, cytolysis and nuclear aggregation. Tissue impairments in the brain and testes were detected in 32d; cell cavitation, cytomorphosis and blurred cell boundaries appeared in the brain, while the testes lesions contained spermatogenic cell lesion, decreased mature seminal vesicle, sperm cells gathering, seminiferous tubules disorder and dilated intercellular space. Furthermore, delayed spermatogenesis had occurred. The transcriptional changes of 19 genes along the hypothalamus–pituitary–gonadal–liver (HPGL) axis were investigated across the three organs. The disrupted expression of genes such as Ers, Ars, Vtgs, cyp19a, star, hsd3b, hsd17b3 and shh indicated the possible abnormal steroidogenesis, estrogenic or antiandrogen effects of PrP. Overall, the present results provided evidences for the toxigenicity and endocrine disruptive effects on the male mosquitofish of chronic PrP exposure, which highlights the need for more investigations of its potential health risks.

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Anticonvulsant effect of sodium cyclamate and propylparaben on pentylenetetrazol‐induced seizures in zebrafish

Cited by 13 publications

References 43 publications

Anti-High Mobility Group Box-1 Monoclonal Antibody Attenuates Seizure-Induced Cognitive Decline by Suppressing Neuroinflammation in an Adult Zebrafish Model

Anti-High Mobility Group Box-1 Monoclonal Antibody Attenuates Seizure-Induced Cognitive Decline by Suppressing Neuroinflammation in an Adult Zebrafish Model

Schaftoside Suppresses Pentylenetetrazol-Induced Seizures in Zebrafish via Suppressing Apoptosis, Modulating Inflammation, and Oxidative Stress

Endocrine Disruption of Propylparaben in the Male Mosquitofish (Gambusia affinis): Tissue Injuries and Abnormal Gene Expressions of Hypothalamic-Pituitary-Gonadal-Liver Axis

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