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Effects of N-acetylcysteine and acetyl-l-carnitine on acute PTZ-induced seizures in larval and adult zebrafish

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Abstract

Background

Epilepsy is a prevalent neurological disease, affecting approximately 1–2% of the global population. The hallmark of epilepsy is the occurrence of epileptic seizures, which are characterized by predictable behavioral changes reflecting the underlying neural mechanisms of the disease. Unfortunately, around 30% of patients do not respond to current pharmacological treatments. Consequently, exploring alternative therapeutic options for managing this condition is crucial. Two potential candidates for attenuating seizures are N-acetylcysteine (NAC) and Acetyl-l-carnitine (ALC), as they have shown promising neuroprotective effects through the modulation of glutamatergic neurotransmission.

Methods

This study aimed to assess the effects of varying concentrations (0.1, 1.0, and 10 mg/L) of NAC and ALC on acute PTZ-induced seizures in zebrafish in both adult and larval stages. The evaluation of behavioral parameters such as seizure intensity and latency to the crisis can provide insights into the efficacy of these substances.

Results

Our results indicate that both drugs at any of the tested concentrations were not able to reduce PTZ-induced epileptic seizures. On the other hand, the administration of diazepam demonstrated a notable reduction in seizure intensity and increased latencies to higher scores of epileptic seizures.

Conclusion

Consequently, we conclude that, under the conditions employed in this study, NAC and ALC do not exhibit any significant effects on acute seizures in zebrafish.

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Data availability

The data supporting this study's findings are available in the Open Science Framework at https://osf.io/uezfm/.

Abbreviations

ASD:

Antiseizure drugs

AUC:

Area under the curve

BOD:

Biochemical oxygen demand incubator

CEUA:

Ethics Committee for animal use

CONCEA:

Conselho Nacional de Controle de Experimentação Animal

dpf:

Days post-fertilization

DZP:

Diazepam

GABA:

Gamma-aminobutyric acid

GABAA :

Gamma-aminobutyric acid type A receptor

Grm2 :

Glutamate metabotropic receptor 2 gene

GSH:

Glutathione

ALC:

Acetyl-l-carnitine

MDA:

Malondialdehyde

mGlu2:

Metabotropic glutamate type 2 receptors

mGluRs:

Extra-synaptic metabotropic receptors

NAC:

N-Acetylcysteine

PTZ:

Pentylenetetrazole

UFRGS:

Universidade Federal do Rio Grande do Sul

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Funding

We thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, proc. 303343/2020-6), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES), and Pró-Reitoria de Pesquisa (PROPESQ) at Universidade Federal do Rio Grande do Sul (UFRGS) for funding and support.

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Authors and Affiliations

  1. Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil

    Rafael Chitolina, Carlos G. Reis & Angelo Piato

  2. Laboratório de Psicofarmacologia e Comportamento (LAPCOM), Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil

    Rafael Chitolina, Carlos G. Reis, Thailana Stahlhofer-Buss, Amanda Linazzi & Angelo Piato

  3. Laboratório de Neurobiologia e Psicofarmacologia Experimental (PsychoLab), Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil

    Ana P. Herrmann

  4. School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland

    Radharani Benvenutti

  5. Departamento de Bioquímica, Farmacologia e Fisiologia, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro (UFTM), Uberaba, MG, Brazil

    Matheus Marcon

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Contributions

Conceptualization, RC, and AP; methodology, RC, CGR, RB, TSB, AL, MM, AP; investigation, RC, CGR, RB, TSB, AL, MM; formal analysis, RC, CGR, RB, TSB, AL, MM, AP; resources, AP; writing—original draft, RC; writing—review and editing, RC, CGR, RB, TSB, AL, MM, APH, AP; supervision, AP; funding acquisition, AP.

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Correspondence to Angelo Piato.

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Chitolina, R., Reis, C.G., Stahlhofer-Buss, T. et al. Effects of N-acetylcysteine and acetyl-l-carnitine on acute PTZ-induced seizures in larval and adult zebrafish. Pharmacol. Rep 75, 1544–1555 (2023). https://doi.org/10.1007/s43440-023-00536-7

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