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Gamma-Decanolactone Alters the Expression of GluN2B, A1 Receptors, and COX-2 and Reduces DNA Damage in the PTZ-Induced Seizure Model After Subchronic Treatment in Mice

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Abstract

Gamma-decanolactone (GD) has been shown to reduce epileptic behavior in different models, inflammatory decreasing, oxidative stress, and genotoxic parameters. This study assessed the GD effect on the pentylenetetrazole (PTZ) model after acute and subchronic treatment. We evaluated the expression of the inflammatory marker cyclooxygenase-2 (COX-2), GluN2B, a subunit of the NMDA glutamate receptor, adenosine A1 receptor, and GD genotoxicity and mutagenicity. Male and female mice were treated with GD (300 mg/kg) for 12 days. On the tenth day, they were tested in the Hot Plate test. On the thirteenth day, all animals received PTZ (90 mg/kg), and epileptic behavior PTZ-induced was observed for 30 min. Pregabalin (PGB) (30 mg/kg) was used as a positive control. Samples of the hippocampus and blood were collected for Western Blotting analyses and Comet Assay and bone marrow to the Micronucleus test. Only the acute treatment of GD reduced the seizure occurrence and increased the latency to the first stage 3 seizures. Males treated with GD for 12 days demonstrated a significant increase in the expression of the GluN2B receptor and a decrease in the COX-2 expression. Acute and subchronic treatment with GD and PGB reduced the DNA damage produced by PTZ in males and females. There is no increase in the micronucleus frequency in bone marrow after subchronic treatment. This study suggests that GD, after 12 days, could not reduce PTZ-induced seizures, but it has been shown to protect against DNA damage, reduce COX-2 and increase GluN2B expression.

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Data Availability

The datasets generated during or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This research received financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, 307515/2019-2), and Federal University of Rio Grande do Sul (UFRGS, 36326).

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Authors and Affiliations

  1. Laboratory of Neuropharmacology and Preclinical Toxicology, Health Basic Sciences Institute, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Fernanda Marcelia dos Santos, Pricila Fernandes Pflüger, Leticia Lazzarotto, Mariana Uczay, Wesley Roberto de Aguida & Patrícia Pereira

  2. Laboratory of Pain Pharmacology and Neuromodulation: Pre-Clinical Research. Postgraduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Lisiane Santos da Silva & Iraci Lucena da Silva Torres

  3. Laboratory of Genetic Toxicology, Lutheran University of Brazil, Canoas, RS, Brazil

    Fernanda Brião Menezes Boaretto, Jayne Torres de Sousa & Jaqueline Nascimento Picada

  4. Laboratory of Neuropharmacology and Preclinical Toxicology, Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Sarmento Leite 500/305, Porto Alegre, RS, CEP 90050-170, Brazil

    Patrícia Pereira

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dos Santos, F.M., Pflüger, P.F., Lazzarotto, L. et al. Gamma-Decanolactone Alters the Expression of GluN2B, A1 Receptors, and COX-2 and Reduces DNA Damage in the PTZ-Induced Seizure Model After Subchronic Treatment in Mice. Neurochem Res 46, 2066–2078 (2021). https://doi.org/10.1007/s11064-021-03345-7

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